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1
Signoret-Genest, Jérémy. "Implication physiopathologique du locus coeruleus dans la migraine." Thesis, Université Clermont Auvergne (2017-2020), 2017. http://www.theses.fr/2017CLFAS018.
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Résumé indisponibleTwelve percent of the world population suffers from migraine and its cost is estimated at $18 billion per year in Europe. The frequency of attacks may increase over time in some migraineurs, evolving from episodic migraine (0 to 14 days of migraine/month) to chronic migraine (more than 15 days of migraine/month). Propranolol is one of the major prophylactic treatments of migraine, used to decrease the frequency of the attacks. However, its mechanism of action is largely unknown. Thus, using an animal model of repeated chemical stimulation of the dura, along with behavioural, electrophysiological, and immunohistochemical approaches, we assessed the prophylactic effect of per os propranolol on central sensitisation. It was able to prevent (i) the aggravation and persistence of central sensitisation as well as (ii) the alteration of descending controls of pain (iii) dural stimulation-induced activation of the locus coeruleus (LC). Recording simultaneously from Sp5C and LC then allowed us to demonstrate that (iv) LC integrates both cutaneous and meningeal nociceptive information and (v) LC exerts a facilitatory effect on Sp5C excitability, while in pathological conditions, (vi) integration of trigeminal nociception by LC was decreased while (vii) the modulation of Sp5C by LC was altered. We then tested the effect on central sensitisation of propranolol microinjection in the LC. It (viii) prevented central sensitisation but (ix) couldn’t reverse it. Finally, we investigated the mechanism of action of propranolol in the LC; the results suggested that (x) propranolol alters intrinsic properties of LC, thereby dampening its ability to facilitate Sp5C. In conclusion, our results revealed the facilitatory influence of the LC on trigeminal nociception, suggesting that the LC could play a facilitating role in triggering migraine headaches
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Finlayson, Paul George. "Electrophysiological studies of locus coeruleus neurons in culture." Thesis, University of Ottawa (Canada), 1986. http://hdl.handle.net/10393/21038.
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Delagrange, Philippe. "Locus coeruleus et comportements d'attention chez le chat." Paris 6, 1990. http://www.theses.fr/1990PA066471.
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Des donnees anterieures, chez le chat, ayant indique l'importance de la mediation noradrenergique dans la modulation de l'attente, nous avons recherche la structure noradrenergique controlant ce comportement ainsi que le rythme electrocortical mu, localise dans l'aire si, qui lui est associe. Le marquage par transport retrograde de hrp a mis en evidence la projection du locus coeruleus (lc) sur le foyer thalamique commandant les rythmes mu. Une etude immunocytochimique nous a permis d'etudier des terminaisons noradrenergiques pericellulaires au niveau de ce foyer. Afin de determiner le type de modulation exercee par le lc sur le comportement et l'ecog d'attente, nous avons pratique des desafferentations noradrenergiques par un neurotoxique (dsp4) detruisant specifiquement les terminaisons noradrenergiques issues du lc ainsi que des lesions du lc. Nous concluons que les neurones noradrenergiques du lc exercent une influence inhibitrice sur le comportement d'attente et une exacerbation du comportement d'attention focalisee et des rythmes beta l'accompagnant. Enfin nous avons voulu connaitre le devenir des messages somesthesiques sous l'effet soit du developpement du rythme mu, soit lorsque le systeme noradrenergique est mis en jeu, c'est-a-dire lors d'un accroissement du niveau de vigilance. Nous montrons que pour un stimulus somesthesique donne, le message transthalamique est desorganise seulement pendant les episodes de mu. D'autre part, il nous est apparu que le rapport signal/bruit est plus faible en vigilance intense et augmente lorsque le niveau baisse. Le message serait attenue lorsque l'animal entre dans un etat d'immobilite vigilante
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Dubé, Gilles R. "Modulation of neurotransmission in locus coeruleus by metabotropic glutamate receptors." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ28337.pdf.
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McFadzean, I. "Kappa opioid actions in the rat locus coeruleus in vitro." Thesis, University of Cambridge, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233318.
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Intracellular recordings were made from neurones of the rat locus coeruleus (lc) contained within a brain slice maintained in vitro. When applied to the slice in known concentrations, K opioid receptor agonists produced a concentration-dependent, naloxone-reversible depression of the electrically evoked excitatory post-synaptic potential (epsp). This effect of K agonists was observed in the absence of changes in the membrane potential or input resistance of the post-synaptic cell. Similarly, the K agonists had no effect on the tetrodotoxin-resistant action potential waveform. Naloxone antagonised the response to U50488 with an apparent dissociation equilibrium constant (Kd) of 28 nM, consistent with the response being mediated via K opioid receptors. In contrast, u opioid receptor agonists caused a membrane hyperpolarisation concomitant with a fall in neuronal input resistance, and depressed the tetrodotoxin-resistant action potential. These effects were concentration-dependent and antagonised by naloxone; the hyperpolarising action of [D-Ala2 , NMePhe4 , Gly-ol5 ] enkephalin (DAGO) was antagonised by naloxone with a Kd of 1.5 nM. These findings are in agreement with previous reports that u receptor activation increases a potassium conductance in lc neurones. The epsp was depressed, but not abolished, by the excitatory amino acid antagonists, 2-amino-5-phosphonovaleric acid (2APV) and kynurenic acid, suggesting that the epsp was at least partly mediated by an excitatory amino acid. U50488 did not depress the depolarisation produced by local application of L-glutamic acid. In addition to the epsp, a noradrenergic inhibitory post-synaptic potential (ipsp) could be evoked in lc neurones. U50488 depressed the ipsp, but this effect was not reversed by naloxone and therefore not mediated via opioid receptors. U50488 had no effect on the all or nothing depolarising potential which could be evoked in a proportion of lc neurones. The effect of U50488 on the epsp was reduced when experiments were performed in the presence of agents - either barium, quinine or 4-aminopyridine - which block potassium conductances. An in vitro autoradiographic study of 3 H bremazocine binding within the lc revealed that the majority of binding was displaced by a combination of unlabelled DAGO and [D-Ser2 ] Leu enkephalin Threonine (DLSET) and so represented u sites. A significant proportion however, was displaceable by unlabelled U50488 and thus represented K binding sites. It is concluded that K opioid receptors are situated pre-synaptically within the lc and when activated depress excitatory synaptic transmission.
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Perna, Marla K., Katalin Szebeni, Craig A. Stockmeier, and Gregory A. Ordway. "Glia in the Locus Coeruleus in Major Depression and Suicide." Digital Commons @ East Tennessee State University, 2007. https://dc.etsu.edu/etsu-works/8623.
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Recent postmortem studies have demonstrated deficits in glia in major depressive disorder, including reductions in the astrocyte specific interfilament glial fibrillary acidic protein (GFAP) in the prefrontal cortex and cerebellum of depressed patients. Astrocytes serve important roles in influencing neuronal activity in the CNS, one of which is to remove neurotransmitters from the extracellular space. The present study investigated the levels of GFAP in the locus coeruleus (LC) of human subjects. The LC is the principal source of norepinephrine in the brain and neurochemical pathology of the LC has been demonstrated in major depressive disorder (MDD) and suicide. Tissue punches of the LC were obtained from postmortem brains collected from subjects with MDD who died by suicide and psychiatrically normal control subjects (n=9 per group). The age of the subjects ranged from 17 to 65 years (control 37±4 y; MDD 39±5 y) and postmortem intervals ranged from 17 to 44 h (control 20±1 h; MDD 25±3 h). GFAP-immunoreactivity (ir) was measured by quantitative Western blotting. Alpha-tubulin-ir was used to control for protein loading and transfer. Amounts of GFAP-ir were highly variable within both control and MDD subjects, ranging 15-fold across control subjects and 24-fold across MDD subjects. There was a modest trend for lower GFAP-ir in the LC from MDD subjects relative to control subjects, but this difference was not significantly different. In control subjects, there was no significant correlation of GFAP-ir levels with age. In contrast, GFAP-ir levels were positively correlated with age in MDD subjects. In younger MDD subjects (<40 y), GFAP-ir was consistently lower as compared to matched control subjects. Amounts of GFAP-ir did not correlate with postmortem intervals. These findings are consistent with a previous report demonstrating age effects on GFAP in frontal cortex in depressed but not control subjects. Glia deficits reported in frontal cortex and cerebellum from depressed subjects may also occur in the brainstem, and these deficits may contribute to disruption of monoamine chemistry in depression. Given the variability of GFAP levels in the LC between subjects, other markers of glia should be pursued to evaluate the potential role of glia in brainstem pathology associated with MDD.
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ISAIAS, IOANNIS UGO. "A ROLE FOR LOCUS COERULEUS IN PARKINSON TREMOR - EXPERIMENTAL STUDIES." Doctoral thesis, Università degli Studi di Milano, 2013. http://hdl.handle.net/2434/215235.
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Although Parkinson disease (PD) is characterized by the degeneration of nigrostriatal dopamine (DA) neurons, historic and more recent anatomopathological studies documented also an involvement of the serotonergic and cholinergic systems as well as a profound loss of neurons from the locus coeruleus (LC), the major noradrenergic (NAergic) nucleus in the brain.
In the following studies, I will provide preliminary evidence of a new provocative hypothesis on the significance of LC in conditioning Parkinson tremor. In particular, I speculate that, early at a disease stage, patients with PD and tremor might have an (hyper-)active LC-NAergic system, which would play a key role in the appearance of tremor itself. Furthermore, given a putative compensatory and possibly neuroprotective mechanism of noradrenaline (NA), an intact or hyper-active NAergic system would be responsible for, and support the clinical observation of, a slower disease progression in PD patients with tremor. When verified, this hypothesis will define, for the first time at a physio-pathological level, two different clinical phenotypes (i.e. tremor dominant and akinetic-rigid PD) and possibly suggest new interventional strategies (targeting the NAergic system) to modify disease progression.
A number of drugs that can modulate the NAergic system already exist, ripe for testing. There is no cure for PD, and understanding the cause and progression of the neurodegenerative process is as challenging as it is necessary.
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Grindstaff, Ryan Jerrod. "Arterial baroreceptor regulation of vasopressin release." free to MU campus, to others for purchase, 2000. http://wwwlib.umi.com/cr/mo/fullcit?p9974636.
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Berglöf, Elisabet. "Dopamine neurons in ventral mesencephalon : interactions with glia and locus coeruleus." Doctoral thesis, Umeå universitet, Histologi med cellbiologi, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1667.
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Parkinson’s disease is a progressive neurodegenerative disorder, characterized by a depletion of the dopaminergic neurons in the substantia nigra. The cause of the disease is yet unknown but age, oxidative stress, and neuroinflammation are some of the features involved in the degeneration. In addition, substantial cell death of noradrenergic neurons occurs in the locus coeruleus (LC). Noradrenaline has been suggested to protect the dopamine neurons from oxidative stress and neuroinflammation. The main treatment of Parkinson’s disease is Levo-dopa, although severe side effects arise from this therapy. Hence, grafting fetal ventral mesencephalic (VM) tissue into the adult striatum has been evaluated as an alternative treatment for Parkinsons’s disease. However, the survival of the grafted neurons is limited, and the dopamine-denervated striatum does not become fully reinnervated. Therefore, elucidating factors that enhance dopamine nerve fiber formation and/or survival of the grafted neurons is of utmost importance. To investigate dopamine nerve fiber formation and the interactions with glial cells, organotypic VM tissue cultures were utilized. Two morphologically different nerve fiber outgrowths from the tissue slice were observed. Nerve fibers were initially formed in the absence of migrating astrocytes, although thin vimentin-positive astrocytic processes were detected within the same area. A second, persistent nerve fiber outgrowth was observed associated with migrating astrocytes. Hence, both of these nerve fiber outgrowths were to some extent dependent on astrocytes, and appeared as a general feature since this phenomenon was demonstrated in β-tubulin, tyrosine hydroxylase (TH), and aldehyde dehydrogenase A1 (ALDH1)-positive nerve fibers. Neither oligodendrocytes (NG2-positive cells), nor microglia (Iba-1-positive cells) exerted any effect on these two neuronal growths. Since astrocytes appeared to influence the nerve fiber formation, the role of proteoglycans, i.e. extracellular matrix molecules produced by astrocytes, was investigated. β-xyloside was added to the cultures to inhibit proteoglycan synthesis. The results revealed a hampered astrocytic migration and proliferation, as well as a reduction of the glia-associated TH-positive nerve fiber outgrowth. Interestingly, the number of cultures displaying the non-glia-mediated TH-positive nerve fibers increased after β-xyloside treatment, although the amount of TH-protein was not altered. Thus, proteoglycans produced by astrocytes appeared to be important in affecting the dopamine nerve fiber formation. The noradrenaline neurons in LC have been suggested to protect dopamine neurons from damage. Therefore, the interaction between VM and LC was evaluated. Using the intraocular grafting method, fetal VM and LC were grafted either as single grafts or as VM+LC co-grafts. Additionally, the recipient animals received 2% blueberry-enriched diet. The direct contact of LC promoted graft volume and survival of TH-positive neurons in the VM grafts. The number of dopamine neurons, derived preferably from the A9 (ALDH1/TH-positive) was increased, whereas the dopamine neurons from the A10 (calbindin/TH-positive) were not affected. A dense dopamine-β-hydroxylase (DBH)-positive innervation was correlated to the improved survival. Blueberry-enriched diet enhanced the number of TH-positive neurons in VM, although the graft size was not altered. The combination of blueberries and the presence of LC did not yield additive effects on the survival of VM grafts. The attachment of VM or the addition of blueberries did not affect the survival of TH-positive neurons in LC grafts. The number of Iba-1-positive microglia was decreased in co-grafted VM compared to single VM transplants. The addition of blueberries reduced the number of Iba-1-positive microglia in single VM transplants. Hence, the direct contact of LC or the addition of blueberries enhanced the survival of VM grafts. Taken together, these data demonstrate novel findings regarding the importance of astrocytes for the nerve fiber formation of dopamine neurons. Further, both the direct attachment of LC or antioxidant-enriched diet promote the survival of fetal VM grafts, while LC is not affected.
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Karolewicz, Beata, Laurel Johnson, Katalin Szebeni, Craig A. Stockmeier, and Gregory A. Ordway. "Glutamate Signaling Proteins and Tyrosine Hydroxylase in the Locus Coeruleus of Alcoholics." Digital Commons @ East Tennessee State University, 2008. https://dc.etsu.edu/etsu-works/8610.
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It has been postulated that alcoholism is associated with abnormalities in glutamatergic neurotransmission. This study examined the density of glutamate NMDA receptor subunits and its associated proteins in the noradrenergic locus coeruleus (LC) in deceased alcoholic subjects. Our previous research indicated that the NMDA receptor in the human LC is composed of obligatory NR1 and regulatory NR2C subunits. At synapses, NMDA receptors are stabilized through interactions with postsynaptic density protein (PSD-95). PSD-95 provides structural and functional coupling of the NMDA receptor with neuronal nitric oxide synthase (nNOS), an intracellular mediator of NMDA receptor activation. LC tissue was obtained from 10 alcohol-dependent subjects and eight psychiatrically healthy controls. Concentrations of NR1 and NR2C subunits, as well as PSD-95 and nNOS, were measured using Western blotting. In addition, we have examined tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of norepinephrine. The amount of NR1 was lower in the rostral (-30%) and middle (-41%) portions of the LC of alcoholics as compared to control subjects. No differences in the amounts of NR2C, PSD-95, nNOS and TH were detected comparing alcoholic to control subjects. Lower levels of NR1 subunit of the NMDA receptor in the LC implicates altered glutamate-norepinephrine interactions in alcoholism.
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Duszkiewicz, Adrian Jacek. "Optogenetic dissection of the dopaminergic circuitry involved in memory consolidation." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/23496.
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The ‘synaptic tagging-and-capture’ (STC) theory of cellular memory consolidation holds that memory persistence can be altered by prior or subsequent patterns of neural activity (Redondo & Morris 2011). The aim of this thesis was to develop a realistic model of everyday memory for mice and use the optogenetic toolbox to investigate the neuromodulatory circuitry that modulates persistence of everyday spatial memories. The task involved learning a win-stay rule with the daily goal of finding the location of food in the event arena. Using the developed task, it was confirmed that unrelated novel experiences can facilitate the persistence of spatial memory in a manner sensitive to pharmacological blockade of hippocampal dopamine D1/D5 receptors. Further analysis focused on identifying the specific neuromodulatory systems that mediate this effect. An influential model called the ‘hippocampus- VTA loop’ (Lisman & Grace 2005) points to the critical role of dopaminergic neurons in the ventral tegmental area (VTA), but recent evidence also implicates locus coeruleus (LC) as a potential source of dopamine in the hippocampus (Smith & Greene 2012). In order to identify the dopaminergic structure(s) that may mediate the novelty effect on memory persistence, single unit activity of optogenetically identified catecholaminergic (CAergic) neurons in mouse VTA and LC was recorded in a novelty exploration paradigm. Using tyrosine hydroxylase-Cre knock-in mice and a Cre-dependent adeno-associated viral vectors, CAergic neurons in VTA and LC were selectively tagged with channelrhodopsin-2 (ChR2). Conditional ChR2 expression made it possible to reliably identify CAergic neurons during unit recording sessions in freely moving animals. The main conclusion of the study is that that CAergic neurons in both VTA and LC selectively increase their firing rates in novel environments, relative to both a familiar environment and a home cage baseline. When normalised to their average baseline firing rates, LC neurons are more strongly activated by novelty than VTA neurons. In the final experiment outlined in this thesis, another cohort of Th-Cre mice, in which ChR2 was expressed in CAergic neurons of both VTA and LC using a Cre-dependent adeno-associated virus, was trained on the everyday appetitive spatial memory task. ChR2-mediated photoactivation of CAergic neurons in LC but not in VTA 30 min after encoding, substituting for novelty, was successful in enhancing the persistence of memory. Paradoxically, the effect of optogenetic LC activation was blocked by hippocampal microinfusion of dopamine D1/D5 receptor antagonist but not β-adrenergic receptor antagonist. Results of experiments described in this thesis support the principle of STC theory and collectively indicate that dopamine released from hippocampal terminals of LC neurons mediates the novelty effect on memory persistence. Importantly, they also point to a more general of role of LC in gating of entry to long-term memory.
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Xiang, Lianbin, Katalin Szebeni, Craig A. Stockmeier, Samuel S. Newton, and Gregory A. Ordway. "Microarray Analysis of Gene Expression in the Noradrenergic Locus Coeruleus in Major Depression." Digital Commons @ East Tennessee State University, 2006. https://dc.etsu.edu/etsu-works/8621.
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Previous studies have demonstrated specific biochemical abnormalities in the noradrenergic locus coeruleus (LC) that are strongly associated with major depressive disorder (MDD). Here, we studied the LC of 4 pairs of MDD and matched control subjects by gene expression microarray analysis in an effort to accelerate the discovery of pathobiological abnormalities of these cells in MDD. Among matching criteria, pH values of control (6.71±0.06) and MDD (6.66±0.12) subjects were closely matched. Gene expression profiling using whole human genome microarrays (Agilent) revealed statistically significant changes in approximately 50 transcripts in the LC of depressive subjects. Quantitative real-time PCR (qPCR) was used to analyze transcripts identified by microarray anlayses. In initial studies of 11 of these transcripts that demonstrated a >2-fold change in microarrays, only 3 transcripts were confirmed by qQPCR in a larger sample of 11-12 pairs of MDD and matched control subjects. Amounts of bone morphogenetic factor-7 (BMP7; p=0.001) and potassium channel subfamily K, member 7 (KCNK7; p=0.049) mRNAs were significantly lower in MDD subjects compared to control subjects (~2-fold difference). In contrast, neurolysin mRNA levels were significantly higher (~3-fold; p=0.03) in MDD than in control subjects. BMP7 is a member of the TGF-β superfamily and has neuroprotective and neurotrophic effects on catecholaminergic neurons. The KCNK family of potassium channels contribute to the excitability of neurons. Neurolysin is a zinc-dependent metallopeptidase involved in neuropeptide metabolism. The present study is the first report of these novel gene expression abnormalities in the LC of MDD subjects. These findings enhance our understanding of the pathobiology of MDD and may represent novel targets for pharmacological management of depression.
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Gorea, Eugen. "Régulation sérotoninergique de l'activité électrique du Locus Coeruleus : étude pharmacologique des récepteurs impliqués." Paris 11, 1988. http://www.theses.fr/1988PA112335.
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L'influence du système sérotoninergique sur l'activité des neurones noradrénergiques du locus coeruleus (LC) a été démontrée dans plusieurs études anatomiques, biochimiques et électrophysiologiques. Cependant, les données expérimentales font apparaître des contradictions concernant la nature de cette influence (inhibition, excitation, modulation), la voie anatomique qui la véhicule et le type de récepteur 5-HT impliqué. Les études présentées dans cette thèse montrent que le système sérotoninergique exerce sur la décharge coeruléenne une influence inhibitrice impliquant des récepteurs de type 5-HT2 post-synaptiques dont le site n'est pas le LC. Nos données expérimentales indiquent aussi que la lésion d'une des principales structures afférentes du LC, le noyau prepositus hypoglossi (PrH), supprime les effets des composés 5-HT2 sur l'activité unitaire coeruléenne. Cependant, l'injection locale de ces composés dans le PrH n'a aucun effet sur la décharge des neurones coeruléens. A partir de ces résultats il est conclu que le contrôle sérotoninergique du LC implique un circuit plurisynaptique dans lequel le PrH serait le dernier relais. Absents de ce noyau, les récepteurs 5-HT2 contrôlant la décharge coeruléenne devraient se situer dans les structures afférentes au PrH.
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Gorea, Eugen. "Régulation sérotoninergique de l'activité électrique du Locus coeruleus étude pharmacologique des récepteurs impliqué /." Grenoble 2 : ANRT, 1988. http://catalogue.bnf.fr/ark:/12148/cb37614016x.
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Gonzalez, Mónica María del Carmen. "Rôle du locus coeruleus dans les mécanismes du rebond de sommeil chez le rat." Lyon 1, 1997. http://www.theses.fr/1997LYO1T164.
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Dourado, Débora de Carvalho. "Dimorfismo sexual da função quimiorreceptora a CO2/pH dos neurônios noradrenérgicos no Locus coeruleus." Universidade Federal de São Carlos, 2014. https://repositorio.ufscar.br/handle/ufscar/1254.
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The Locus coeruleus (LC) has been suggested as a CO2 chemoreceptor site in mammals. Most of the studies involving the role of LC in hypercapnic ventilatory response have been performed in males. Since, ovarian steroids modulate the activity of LC neurons and females have a different respiratory response to CO2 of males, we evaluated the activity of LC noradrenergic neurons during normocapnia and hypercapnia in diestrus, ovariectomized (OVX; 0,2 mL/rat of corn oil, s.c., for 3 days) and estradiol-treated ovariectomized (OVX+E2; 10 μg/0,2 mL/rat, s.c., for 3 days) female rats and in intact, orchidectomized (ORX; 0,2 mL/rat of corn oil, s.c., for 7 days), testosterone-treated orchidectomized (ORX+T; 0,25 mg/0,2 mL/rat, s.c., for 7 days) and estradiol-treated orchidectomized (ORX+E2; 10 μg/0,2 mL/rat, s.c., for 3 days) male rats by using double-label immunohistochemistry to c-Fos/TH. Additionally, we assessed the role of noradrenergic LC neurons in OVX and OVX+E2 females on respiratory response to hypercapnia by using 6-hydroxydopamine. Hypercapnia (7% CO2) increased the double-staining (c-Fos/TH-ir) in LC neurons in all groups when compared to air exposure. In the OVX+E2 group there was attenuation in the c-Fos expression in normocapnia and hypercapnia. Hypercapnia increased ventilation in OVX and OVX+E2 groups, which resulted from increases of respiratory frequency (fR) and tidal volume (VT) in sham and 6-OHDA-lesioned groups. The hypercapnic ventilatory response was significantly decreased in 6-OHDA-lesioned rats compared with sham group (29.4% in OVX group and 28.7% in OVX+E2 group) due to a reduced VT in OVX+E2 group and in OVX group due to a decrease in VT and fR. A reduction in TH+ neurons (~61% in OVX and OVX+E2 group) was observed seven days after the microinjections of 6-OHDA in the LC. LC chemical lesion and estradiol did not affect body temperature (Tb). However, hypercapnia caused reduction in Tb of sham (OVX 10 and OVX+E2) and lesioned groups. Thus, we can conclude that noradrenergic neurons in the LC of female and male rats are activated by CO2. However, in OVX+E2 group, estradiol reduced the immunoreactivity compared to OVX group during normocapnia and hypercapnia. Additionally, LC noradrenergic neurons play role in hypercapnic ventilatory response in females but do not affect temperature regulation during normocapnic and hypercapnic conditions.
O Locus coeruleus (LC) é uma área quimiossensível ao CO2 em mamíferos. A maioria dos estudos envolvendo a participação do LC na resposta ventilatória a hipercapnia é realizada em machos. Visto que esteróides ovarianos modulam a atividade de neurônios do LC e fêmeas apresentam uma resposta respiratória ao CO2 diferente de machos, nós avaliamos a atividade dos neurônios noradrenérgicos do LC durante normocapnia e hipercapnia em ratas ciclando em diestro, ovariectomizadas (OVX; 0,2 mL/rata de óleo de milho, s.c., por 3 dias) e ovariectomizadas tratadas com estradiol (OVX+E2; 10 μg/0,2 mL/rata, s.c., por 3 dias) e em ratos intactos, orquidectomizados (ORX; 0,2 mL/rato de óleo de milho, s.c., por 7 dias), orquidectomizados tratados com testosterona (ORX+T; 0,25 mg/0,2 mL/rato, s.c., por 7 dias) e tratados com estradiol (ORX+E2; 10 μg/0,2 mL/rato, s.c., por 3 dias) usando dupla-marcação imunoistoquímica para c-Fos/TH. Adicionalmente, nós avaliamos a participação dos neurônios noradrenérgicos do LC em fêmeas OVX e OVX+E2 na resposta respiratória a hipercapnia usando a neurotoxina 6-hidroxidopamina. A hipercapnia (7% CO2) aumentou a dupla marcação (c-Fos/TH-ir) nos neurônios do LC em todos os grupos comparados a normocapnia. No grupo OVX+E2 houve uma atenuação da expressão de c-Fos no LC em normocapnia e hipercapnia. A hipercapnia causou aumento na ventilação nos grupos OVX e OVX+E2, o qual resultou do aumento da frequência respiratória (fR) e volume corrente (VT) nos grupos controle e lesados. A resposta ventilatória a hipercapnia foi significativamente atenuada no grupo lesado comparado ao grupo controle (29,4% no grupo OVX e 28,7% no grupo OVX+E2) devido à queda no VT no grupo OVX+E2 e no grupo OVX foi devido a queda no VT e na fR. Observamos uma redução de neurônios noradrenérgicos (~61% nos grupos OVX e OVX+E2) sete dias após microinjeções de 6-OHDA no LC. A lesão química do LC e o 8 estradiol não afetaram a Tc. Entretanto, a hipercapnia promoveu redução na temperatura dos grupos sham (OVX e OVX+E2) e lesado. Assim, nós podemos concluir que os neurônios noradrenérgicos do LC de fêmeas e machos são ativados por CO2. Entretanto, no grupo OVX+E2, o estradiol reduziu a imunorreatividade comparado ao grupo OVX durante normocapnia e hipercapnia. Adicionalmente, os neurônios noradrenérgicos do LC de fêmeas participam da resposta ventilatória a hipercapnia, mas não participam da regulação da temperatura durante condições normocápnicas e hipercápnicas.
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Chandley, Michelle J., Katalin Szebeni, Attila Szebeni, Jessica Crawford, Craig A. Stockmeier, Gustavo Turecki, Jose Javier Miguel-Hidalgo, and Gregory A. Ordway. "Gene Expression Deficits in Pontine Locus Coeruleus Astrocytes in Men With Major Depressive Disorder." Digital Commons @ East Tennessee State University, 2013. https://doi.org/10.1503/jpn.120110.
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Background: Norepinephrine and glutamate are among several neurotransmitters implicated in the neuropathology of major depressive disorder (MDD). Glia deficits have also been demonstrated in people with MDD, and glia are critical modulators of central glutamatergic transmission. We studied glia in men with MDD in the region of the brain (locus coeruleus; LC) where noradrenergic neuronal cell bodies reside and receive glutamatergic input.
Methods: The expression of 3 glutamate-related genes (SLC1A3, SLC1A2, GLUL) concentrated in glia and a glia gene (GFAP) were measured in postmortem tissues from men with MDD and from paired psychiatrically healthy controls. Initial gene expression analysis of RNA isolated from homogenized tissue (n = 9-10 pairs) containing the LC were followed by detailed analysis of gene expressions in astrocytes and oligodendrocytes (n = 6-7 pairs) laser captured from the LC region. We assessed protein changes in GFAP using immunohistochemistry and immunoblotting (n = 7-14 pairs).
Results: Astrocytes, but not oligodendrocytes, demonstrated robust reductions in the expression of SLC1A3 and SLC1A2, whereas GLUL expression was unchanged. GFAP expression was lower in astrocytes, and we confirmed reduced GFAP protein in the LC using immunostaining methods.
Limitations: Reduced expression of protein products of SLC1A3 and SLC1A2 could not be confirmed because of insufficient amounts of LC tissue for these assays. Whether gene expression abnormalities were associated with only MDD and not with suicide could not be confirmed because most of the decedents who had MDD died by suicide.
Conclusion: Major depressive disorder is associated with unhealthy astrocytes in the noradrenergic LC, characterized here by a reduction in astrocyte glutamate transporter expression. These findings suggest that increased glutamatergic activity in the LC occurs in men with MDD.
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Feng, Chengyuan. "Sources and targets of trophic factors in the avian locus coeruleus and oculomotor system." abstract only (UNR users only), 2009. http://0-gateway.proquest.com.innopac.library.unr.edu/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3355579.
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LOCARNO, ANDREA. "Neuromodulated plasticity of the connectivity between the Prefrontal Cortex and the noradrenergic Locus Coeruleus." Doctoral thesis, Università degli studi di Genova, 2020. http://hdl.handle.net/11567/995951.
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Incentive stimuli and environmental stressors are encoded at the level of the prefrontal cortex (PFC) circuits, which send their glutamatergic excitatory projections to several neuromodulatory regions, including the Locus Coeruleus (LC), the major source of noradrenaline (NA) for the entire forebrain. Despite the potential implications for NA-mediated regulation of action control and for the etiology of stress-related neuropsychiatric conditions, it remains to be established how LC neuronal activity is shaped by impinging PFC inputs (PFCLC) to affect behavior, and whether these inputs are modulated by in-vivo experience. By combining neurophysiological and optogenetic approaches together with behavioral paradigms in mice, we found that PFC LC stimulation supports learning and retrieval of contextual memory associations. Consistent with the occurrence of plasticity processes at LC synapses, long-lasting modulation of PFCLC projections relies on the endocannabinoid (eCB)-mediated signaling capacity, which is dynamically shaped by context adaptations and stress salience experiences. We also found that eCB-plasticity at PFC → LC synapses is regulated during the adolescence to adulthood transition. In summary, our results not only dissect the behavioral implications of neuromodulated plasticity at PFC inputs to the LC, but also unveil divergent synaptic substrates during postnatal development, which might be relevant to explain some of the different noradrenergic-mediated response in adolescents and adults.
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MISEVICIUTE, IEVA. "Experience-dependent plasticity of Locus Coeruleus glutamatergic synapses during the adolescence to adulthood transition." Doctoral thesis, Università degli studi di Genova, 2021. http://hdl.handle.net/11567/1045652.
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The prefrontal cortex (PFC) integrates emotion and cognitive control upon novel salient experiences, and it provides one of the main cortical glutamatergic inputs to the neuromodulatory nucleus Locus Coeruleus (LC), the major source of Norepinephrine (NE) for the entire forebrain. The LC is promptly recruited by salient and arousing stimuli, and through NE release, modulates the animals’ internal states and behavior. While the role of LC-mediated NE release in target brain regions has been extensively studied, it remains to be established how LC activity is shaped by impinging PFC inputs. Adaptive changes at the PFC→LC synapse may occur upon exposure to salient novel experience, or during critical developmental periods for PFC maturation, like adolescence. During adolescence, the maturation of the PFC is protracted, and emotional responses are mainly driven by subcortical brain regions, such as the Central Nucleus of the Amygdala (CeA). Notably, CeA sends strong Corticotropin-releasing factor (CRF)-containing innervation to the LC; the contribution of this neuropeptidergic input to the modulation of PFC afferents across different post-natal developmental stages is unknown.
We combined neurophysiological, optogenetic, and behavioral approaches to probe the PFC→LC synapses at two different age-periods. Our data show that PFC→LC synapses undergo developmental changes in synaptic strength and long-term synaptic plasticity mechanisms. This is accompanied by differences in valence assignment to novel stimuli and divergent dynamic modulation of the Endocannabinoid signaling (eCB) in adolescents compared to adult mice. Finally, we provide evidence of developmentally regulated functional interaction between the CRF and the eCB signaling in the LC.
In summary, our results reveal a new mechanism of experience-dependent neuromodulated plasticity at PFC→LC synapses and uncover diverse molecular players involved in shaping these synapses during the transition from adolescence to adulthood. Our findings contribute to the understanding of how LC activity is regulated by cortical and subcortical inputs during different neurodevelopmental stages.
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Malinge, Myriam. "Effet des agonistes de la cholecystokinine dans un modele experimental de sevrage a la morphine." Nantes, 1994. http://www.theses.fr/1994NANT19VS.
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SCRIBE, MYRIAM. "Etude du controle des relations motrices entre le sphincter anal externe et la vessie : etude experimentale chez l'homme." Aix-Marseille 2, 1993. http://www.theses.fr/1993AIX20840.
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Guedj, Carole. "Modulation noradrénergique de l’attention." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSE1294/document.
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La neuromodulation apporte une extraordinaire richesse à la dynamique des réseaux de neurones. Parmi les neuromodulateurs du système nerveux central, la noradrénaline permettrait de faciliter l'adaptation du comportement face aux variations des contraintes environnementales en modulant l'attention, cette fonction au coeur de la cognition qui nous permet de sélectionner l'information la plus pertinente en fonction de notre but. Ce processus complexe qui opère à chaque instant à la fois dans l'espace et le temps, constitue une étape essentielle dans cette adaptation comportementale. Cependant, à ce jour, les mécanismes par lesquels ce neuromodulateur exerce ses effets sur le cerveau sain demeurent mal connus. Mon travail de thèse a pour objectif d'examiner les déterminants comportementaux et les marqueurs neuronaux de l'effet stimulant des agonistes noradrénergiques. La question posée était : "Comment la noradrénaline agit-elle pour optimiser l'attention?" Pour répondre à cette question, j'ai choisi de combiner la pharmacologie, l'analyse du comportement, et l'imagerie par résonnance magnétique fonctionnelle chez le singe. Un des principaux résultats de mes travaux est que l'administration d'agents noradrénergiques induit une large réorganisation des réseaux cérébraux, qui pourrait être à l'origine de l'optimisation des réponses comportementales observées parallèlementNeuromodulation provides an extraordinary wealth to the dynamics of neural networks. Among the neuromodulators of the central nervous system, noradrenaline would facilitate behavioral adaptation facing variations of environmental constraints by modulating attention, this function at the heart of cognition that allows us to select the most relevant information based our goal. This complex process that operates at every moment both in space and time, is an essential step in this behavioral adaptation. However, to date, the mechanisms by which this neuromodulator exerts its effects on healthy brain remain unknown. My thesis aims to examine the behavioral and neural markers of the boosting effect of noradrenergic agonists. The question asked was: "How does noradrenaline optimize attention?" To answer this question, I chose to combine pharmacology, behavior analysis, and functional Magnetic Resonance Imaging in monkeys. One of the main results of my work is that the administration of noradrenergic agents induced a large-scale brain networks reorganization, which could be responsible for optimizing behavioral responses observed in parallel
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Carvalho-Costa, Priscila Gonçalves de. "Avaliação da ativação da via HO-CO-GMPc do locus coeruleus na modulação da ansiedade e da nocicepção em ratos." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/59/59134/tde-09122013-135537/.
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O gás composto monóxido de carbono (CO), está envolvido na modulação de diferentes funções orgânicas, tais como a regulação cardiovascular, a temperatura corporal e a nocicepção. A participação do CO nos processos fisiológicos ocorre por meio da atividade da enzima heme-oxigenase (HO), e seu produto CO, o qual por sua vez aumenta a produção de guanosina monofosfato ciclíco intracelular (GMPc). De particular interesse, o locus coeruleus possui elevada expressão da enzima HO-2 sugerindo o envolvimento do gasotransmissor CO na modulação das funções executadas por esta estrutura encefálica. O objetivo deste trabalho foi avaliar o envolvimento da via HO-CO do LC na modulação da ansiedade, avaliada pelo teste de labirinto em cruz elevado e teste claro-escuro; nocicepção aguda, avaliada pelo teste de retirada de cauda e a nocicepção inflamatória, avaliada pelo teste de formalina em ratos. Para atingir estes objetivos, ratos (± 250grs; Wistar) foram anestesiados (ketamina 75 mg/kg e xilasina 10 mg/kg i.m.) e submetidos à cirurgia estereotáxica para implante unilateral de cânulas-guias direcionadas para o LC, e para o ventrículo lateral. Após o período de recuperação, os ratos foram divididos em distintos grupos experimentais para administração intra-LC do ZnDPBG (inibidor inespecífico da enzima HO, nas doses 5,50 ou 200 nmol/0,1 µl) ou seu veículo, Na2CO3 (50 mmol/0,1 µl); do Heme-lisinato (150, 300 ou 600 nmol/0,1 µl) ou seu veículo, L-lisina (14,2 µmol/0,1 µl); do ODQ i.c.v. (inibidor específico da enzima guanilase ciclase solúvel, 1,3 nmol/1,0 µl) ou seu veículo (DMSO 1%, 1,0 µl) e após 15 min o Heme-lisinato (600 nmol/0,1 µl) ou seu veículo (L-lisina, 14,2 µmol/0,1 µl), intra-LC. Após o tempo de 15 min, os ratos foram avaliados no teste de LCE ou no TCE por 5 minutos, no teste de retirada de cauda por 120 minutos e no teste de formalina intra-podal por 45 minutos. Os resultados obtidos mostram que o aumento da produção do neuromodulador gasoso CO no LC, pela ativação da via HO-CO-GMPc com Heme-lisinato, promove efeito ansiolítico avaliado no teste do LCE e no TCE, evidenciado pelo aumento do tempo de permanência e pelo aumento do número de entradas nos braços abertos do LCE, e pelo aumento tempo de permanência no compartimento claro do TCE. Este efeito ansiolítico é dependente da atividade de GMPc intracelular, desde que o tratamento i.c.v. com inibidor específico da enzima GCs bloqueou os efeitos do Heme-lisinato no LCE e no TCE. Ainda, a ativação da via HO-CO-GMPc por meio da administração intra-LC do Heme-lisinato promoveu efeito antinociceptivo frente estímulo térmico agudo (teste de retirada de cauda em ratos), sendo este efeito dependente da atividade do GMPc, desde que o pré-tratamento com o inibidor da enzima guanilase ciclase solúvel, ODQ, bloqueou o aumento do IARC. O bloqueio da via HO-CO promove efeito hipernociceptivo em modelo de dor inflamatória, desde que o tratamento intra-LC com inibidor inespecífico da HO, ZnDPBG aumenta o número de sacudidas no teste de formalina intra-podal. Assim, este estudo é pioneiro em demonstrar que o neuromodulador CO do LC modula a ansiedade e a nocicepção aguda térmica e inflamatória.The gas composed carbon monoxide (CO) is involved in the modulation of various physiological functions such as cardiovascular regulation, nociception and body temperature. CO participation in physiological processes occurs through the activity of the enzyme heme oxygenase (HO), and its product CO, which in turn increases the production of intracellular cyclic guanosine monophosphate (cGMP). In particular interest, the locus coeruleus (LC) has a high HO-2 enzyme expression suggesting the involvement of CO in the modulation of the functions performed by this brain structure. The aim of this study was to evaluate the involvement of HO-CO pathway of LC in modulating anxiety, assessed by elevated plus maze test and light-dark box test. Additionally, acute nociception, as assessed by the tail flick test and inflammatory nociception, as assessed by formalin test in rats were analyzed after HO-CO pathway activation. Rats (±250 grs; Wistar) were anesthetized (ketamine 75 mg/kg and xylazine 10 mg/kg im) and underwent stereotactic surgery for cannulas guides unilateral implantation directed to the LC, and to the lateral ventricle. After the recovery period, rats were divided into distinct experimental groups for intra-LC ZnDPBG (nonspecific enzyme inhibitor HO doses 5, 50 or 200 nmol/0.l µl) or its vehicle, Na2CO3 (50 mmol/0.l µl); Heme-lysinate (150, 300 or 600 nmol/0.l µl) or its vehicle, L-lysine (14.2 nmol/0.1 µl), the ODQ i.c.v. (specific inhibitor of the enzyme guanilase soluble cyclase, 1.3 nmol/1.0 µl) or its vehicle (1% DMSO, 1.0 µl) and after 15 min the Heme-lysinate (600 nmol/0.1 µl), or its vehicle (L-lysine, 14.2 mmol/0.1 µl), intra-LC. After time 15 min, rats were evaluated in the EPM test or LDB for 5 minutes and in the tail flick test for 120 minutes and in the formalin test for 45 minutes. The results show that CO increased production in LC, by HO-CO-cGMP pathway activation, promotes anxiolytic effect evaluated in the EPM test and LDB. The anxiolytic effect is dependent on the activity of intracellular cGMP, since treatment i.c.v. with enzyme sGC inhibitor blocked the effects of Heme-lysinate. Moreover, the activation of the HO-CO-cGMP pathway into the LC promoted antinociceptive effect in the tail flick test, this effect being dependent on the activity of cGMP, since pre-treatment with the guanilase cyclase soluble inhibitor, ODQ, blocked the increase in analgesic index. Furthermore, the block of the HO-CO pathway intra-LC promoted hypernociception in a model of inflammatory pain, since treatment with nonspecific inhibitor HO, ZnDPBG, increases the nociceptive behavior in the formalin test. Thus, this study is the first to demonstrate that the CO neuromodulator into LC modulates anxiety and acute thermal and inflammatory nociception.
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Bourde, Odile. "La régulation à long terme de l'expression de la tyrosine hydroxylase dans le locus coeruleus : modèles pharmacologique et physiologique." Lyon 1, 1993. http://www.theses.fr/1993LYO1T158.
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Carvalho, Débora de. "Participação dos receptores NK-1 no locus coeruleus na resposta cardiorrespiratória e termorreguladora à hipercapnia." Universidade Federal de São Carlos, 2009. https://repositorio.ufscar.br/handle/ufscar/1309.
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Previous issue date: 2009-05-29Universidade Federal de Minas Gerais
The locus coeruleus (LC) has been suggested as a CO2 chemoreceptor site in mammals. Substance P (SP) has been used as a marker of respiratory neurons and it plays an important role in compensatory responses to hypercapnia in several sites of the central nervous system. Neurokinin-1 (NK-1) receptor immunoreactive (NK1Rir) neurons and processes are widely distributed within the LC. Thus, the present study assessed the role of NK-1 receptors in the LC in the cardiorespiratory and thermal responses to hypercapnia. To this end, substance P-saporin conjugate (SPSAP; 2μM) was injected in the LC to kill NK1R-ir neurons, or IgG-SAP as a control in male Wistar rats. The animals that the drug reached the fourth ventricle (4ºV) were considered as a 4ºV group. Pulmonary ventilation (VE, body plethysmograph), mean arterial pressure (MAP), heart rate (HR) and body core temperature were measured followed by 60 min of hypercapnic exposure (7% CO2). To verify the correct placement and effectiveness of the chemical lesions, immunohistochemistry for NK1R was performed. In addition, tyrosine hydroxylase (TH) immunoreactivity was performed to verify if noradrenergic neurons were eliminated. Fluoro-Jade technique was used to evaluate neuronal degeneration. A reduced NK1R (72% of reduction) and TH immunoreactivity (66% of reduction) was observed seven days after the injections of SP-SAP in the LC and an intense Fluoro-Jade staining, showing the effectiveness of the lesion. Focal lesions of NK1R-ir did not affect basal ventilation in the SP-SAP in LC and SP-SAP in 4ºV groups. Hypercapnia caused an increase in pulmonary ventilation in all groups, which was a result of increases in respiratory frequency (fR) and tidal volume (VT), SP-SAP treatment in the LC and in the fourth ventricle attenuated the hypercapnic ventilatory response (30% and 20%, respectivally), due to a reduction in the VT. SP-SAP in the LC and SP SAP in the 4ºV 11 lesion did not affect MAP, but caused an increase in HR in both groups. The results suggest that NK1R-ir neurons in the LC modulate hypercapnic ventilatory response but play no role in breathing control under resting conditions. Additionally, NK1R-ir neurons seem to play no role in body temperature and MAP regulation in resting conditions and during hypercapnia, but modulate HR during CO2 exposure. This modulation may be due to a change in the noradrenaline release.
O locus coeruleus (LC) é considerado uma região quimiorreceptora a CO2/pH em mamíferos. A substância P (SP) tem sido usada como marcador de neurônios respiratórios, pois possui importante função nas respostas compensatórias a hipercapnia em muitas áreas do sistema nervoso central. Neurônios e processos imunorreativos a receptores neurocinina 1 (NK-1) estão amplamente distribuídos dentro do LC. Portanto, o presente estudo teve por objetivo avaliar a participação de receptores NK-1 no LC nas respostas cardiorrespiratórias e termorreguladoras à hipercapnia. Para este fim, foi injetado o conjugado SP-Saporina (SP-SAP; 2μM) no LC de ratos Wistar para lesar neurônios que expressam esses receptores, ou IgGSAP como controle. Os animais em que as injeções atingiram o quarto ventrículo (4ºV) foram considerados como grupo 4ºV. A ventilação pulmonar (VE, pletismografia de corpo inteiro), pressão arterial média (PAM), freqüência cardíaca (FC) e temperatura corporal (Tc) foram medidas por 60 min de exposição à hipercapnia (7% CO2). Para verificar a correta localização e efetividade da lesão química realizou-se a imunohistoquímica para receptores NK-1. Além disso, imunohistoquímica para tirosina hidroxilase (TH) foi realizada para averigüar se neurônios noradrenérgicos foram lesados. A técnica de Fluoro-Jade foi também utilizada para avaliar a neurodegeneração. Observou-se a redução da imunorreatividade para receptores NK-1 (72% de lesão dos neurônios) e redução da imunorreatividade para neurônios noradrenérgicos (66% dos neurônios noradrenérgicos) sete dias após injeções de SP-SAP no LC e intensa marcação na técnica de Fluoro-Jade mostrando a efetividade da lesão. Lesões seletivas de neurônios que expressam receptores NK-1 no LC não afetaram a ventilação basal, o mesmo foi observado com os animais em que a injeção atingiu o 4ºV. A hipercapnia causou aumento da ventilação pulmonar 9 em todos os grupos decorrente do aumento da freqüência respiratória (fR) e volume corrente (VC). Entretanto, o tratamento com SP-SAP no LC e no 4ºV promoveu atenuação da resposta ventilatória (30% e 20%, respectivamente), devido à diminuição do VC. A lesão com SP-SAP no LC e no 4ºV não afetou a PAM, entretanto promoveu aumento na FC em ambos grupos. Os resultados sugerem que os neurônios que expressam receptores NK-1 no LC modulam a resposta ventilatória à hipercapnia, porém não possuem papel tônico na ventilação em condições basais. Além disso, esses neurônios não participam da regulação da temperatura e da PAM em normocapnia e hipercapnia, mas modulam FC durante exposição ao CO2. Essa modulação pode ser devida a alteração na liberação de noradrenalina.
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Johnson, Luke A. "Locus Coeruleus and Hippocampal Tyrosine Hydroxylase Levels in a Pressure-Overload Model of Heart Disease." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/honors/288.
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Studies have indicated that approximately 30% of people with heart disease experience major depressive disorder (MDD). Despite strong clinical evidence of a link between the two diseases, the neurobiological processes involved in the relationship are poorly understood. A growing number of studies are revealing similar neuroanatomical and neurochemical abnormalities resulting from both depression and heart disease. The locus coeruleus (LC) is a group of neurons in the pons that synthesize and release norepinephrine, and that is known to play a significant role in depression pathobiology. For example, there is evidence that tyrosine hydroxylase (TH) is elevated in the LC in depression. In addition, there is evidence that the LC plays a role in cardiovascular autonomic regulation. The hippocampus is another region that exhibits abnormalities in both depression and heart disease. In this study, the levels of TH in the hippocampus and LC were examined in the guinea pig pressure-overload model of heart disease. TH levels were also measured in the pressure-overload model treated with vagal nerve stimulation, a new investigational therapeutic intervention in heart disease. This study found that there were no changes in TH levels in the LC or the hippocampus of the pressure-overload model or in the pressure-overload model treated with vagal nerve stimulation.
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Saunier, Claude François. "Interactions entre l'anesthésie générale et le système noradrénergique du Locus Coeruleus : approche expérimentale chez le rat." Lyon 1, 1997. http://www.theses.fr/1997LYO1T238.
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Chandley, Michelle J., Attila Szebeni, Katalin Szebeni, Jessica D. Crawford, Craig A. Stockmeier, Gustavo Turecki, Richard M. Kostrzewa, and Gregory A. A. Ordway. "Elevated Gene Expression of Glutamate Receptors in Noradrenergic Neurons From the Locus Coeruleus in Major Depression." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/8599.
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Glutamate receptors are promising drug targets for the treatment of urgent suicide ideation and chronic major depressive disorder (MDD) that may lead to suicide completion. Antagonists of glutamatergic NMDA receptors reduce depressive symptoms faster than traditional antidepressants, with beneficial effects occurring within hours. Glutamate is the prominent excitatory input to the noradrenergic locus coeruleus (LC). The LC is activated by stress in part through this glutamatergic input. Evidence has accrued demonstrating that the LC may be overactive in MDD, while treatment with traditional antidepressants reduces LC activity. Pathological alterations of both glutamatergic and noradrenergic systems have been observed in depressive disorders, raising the prospect that disrupted glutamate-norepinephrine interactions may be a central component to depression and suicide pathobiology. This study examined the gene expression levels of glutamate receptors in post-mortem noradrenergic LC neurons from subjects with MDD (most died by suicide) and matched psychiatrically normal controls. Gene expression levels of glutamate receptors or receptor subunits were measured in LC neurons collected by laser capture microdissection. MDD subjects exhibited significantly higher expression levels of the NMDA receptor subunit genes, GRIN2B and GRIN2C, and the metabotropic receptor genes, GRM4 and GRM5, in LC neurons. Gene expression levels of these receptors in pyramidal neurons from prefrontal cortex (BA10) did not reveal abnormalities in MDD. These findings implicate disrupted glutamatergic-noradrenergic interactions at the level of the stress-sensitive LC in MDD and suicide, and provide a theoretical mechanism by which glutamate antagonists may exert rapid antidepressant effects.
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Xiong, Huangui. "Angiotensin II modulates glutamate-induced depolarizations and synaptic transmission in rat locus coeruleus neurons in vitro." Thesis, University of Ottawa (Canada), 1993. http://hdl.handle.net/10393/6885.
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Considerable evidence now supports a neurotransmitter or neuromodulatory role for angiotensin II (AII) in the central nervous system (CNS). The objectives of this research are to study the actions of AII on spontaneous activity and on Glu-induced responses in rat locus coerulus neurons. The action of AII appears to be selective since it had no effect on the depolarizations evoked by acetylcholine (ACh), or by depolarizing current injections. Selectivity is also indicated by the observation that AII had little or no effect on Glu responses in brain stem neurons outside of the LC where AII receptors have not been reported to be present. AII was also found to be subject to rapid peptidase degradation. When AII was applied by bath perfusion, rather than by iontophoretic or pressure application, it had little or no effect on Glu responses. However, when Sar$\sp1$-AII, an analogue which is resistant to aminopeptidase degradation was bath-applied, or when AII was applied together with peptidase inhibitors, the depressant action on Glu responses was observed. Like AII, angiotensin III (AIII) also had depressant actions on Glu responses in LC neurons, but the action of AIII appeared to be less potent than that of AII. In addition to its strong depressant actions on applied Glu-induced responses, AII was also found to depress responses to synaptically released excitatory amino acids (EAAs). In fact we were able to show that excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation were blocked by Glu receptor antagonists, indicating involvement of EAAs in the mediation of the EPSPs. Sar$\sp1$-AII or AII applied together with peptidase inhibitors depressed the amplitudes of the EPSPs in a concentration dependent manner. The depressant actions of AII on EPSPs were also antagonized by the AT$\sb2$-selective antagonist PD123177, indicating again the involvement of AT$\sb2$ receptors in the mediation of AII action on EAA-induced responses. The functional significance of the depressant action of AII on Glu responses in the LC neurons is at present unclear. It may represent a role for a brain angiotensinergic system in control of cardiovascular functions through modulation of the actions of excitatory amino acid neurotransmitters on LC neuronal activity. (Abstract shortened by UMI.)
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Miranda, Jolene Matos Incheglu de. "Participação do fator de liberação de corticotrofina (CRF) no Locus coeruleus na resposta respiratória à hipercapnia." Universidade Federal de São Carlos, 2015. https://repositorio.ufscar.br/handle/ufscar/7629.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Locus coeruleus (LC) is a pontine noradrenergic group that acts as a central chemoreceptor to CO2/pH and it is involved in the cognitive aspects of stress response and it is associated with a large number of physiological and behavioral processes, including sleepwake cycle, feeding, cardiovascular and respiratory control, nociception, thermoregulation and learning. The LC has also been implicated in the cognitive aspects of stress responses, in part through the action of corticotropin releasing factor (CRF), which when released in these situations increases the firing frequency of LC noradrenergic neurons. CRF is the largest stimulator of the pituitary secretion of ACTH (adrenocorticotropic hormone) and their receptors (types 1 and 2) are widely distributed in the central nervous system, including the LC. Thus, we tested the involvement of CRF1 receptors (CRF1) located in the LC in the ventilatory and thermal responses induced by hypercapnia (7%CO2) in rats. To this end, we injected antalarmin (a CRF1 antagonist, 0.05 and 0,1 μg/0.1 μL) into the LC of male Wistar rats. Pulmonary ventilation (VE) and body temperature (Tb, dataloggers) were measured in air and followed by 7% CO2 in unanesthetized rats. There were no differences in body temperature between groups under normocapnia and hypercapnia. We observed an increased ventilation in normocapnia, at 5 to 15 minutes after microinjection of antalarmin (dose 0.1 μg / 0.1 μL) compared to the control, due to an increase in tidal volume. The hypercapnic response in antalarmine treated animals was higher compared to control groups. The dose of 0.05 μg / 0.1 μL caused an increase in ventilation 15 min after CO2 exposure and this response increased further with the dose of 0.1 μg / 0.1 μL at 30 minutes after hypercapnia, due to an increased tidal volume. Our results suggest that CRF1 receptors in the LC exert a tonic inhibitory role in the ventilation and the inhibitory modulation of the respiratory response to CO2.
O locus coeruleus (LC) é um grupamento noradrenérgico pontino que atua como um quimiorreceptor central a CO2/pH e está associado a um grande número de processos fisiológicos e comportamentais, entre eles, ciclo sono-vigília, alimentação, controle respiratório e cardiovascular, nocicepção, termorregulação e aprendizado. O LC tem sido também implicado nos aspectos cognitivos na resposta ao stress, em parte por meio da ação do fator liberador de corticotrofina (CRF) que, ao ser liberado nessas situações, aumenta a frequência de disparo dos neurônios noradrenérgicos do LC. O CRF é o maior estimulador da secreção hipofisária de ACTH (hormônio adrenocorticotrófico), sendo que seus receptores (tipos 1 e 2) estão difusamente distribuídos no sistema nervoso central (SNC), incluindo o LC. Neste contexto, nós testamos o envolvimento dos receptores CRF1 no LC na resposta respiratória ao CO2 em ratos adultos não anestesiados, por meio da microinjeção de antalarmina (antagonista de CRF1) no LC (0,05 e 0,1 μg / 0,1 μL). A ventilação pulmonar (VE) e a temperatura corporal (Tc, dataloggers) foram medidas no ar e seguido de 7% CO2 em ratos não anestesiados. Não houve alteração na Tc entre os grupos em normocapnia e hipercapnia. Observamos aumento da ventilação em normocapnia, nos tempos de 5 a 15 minutos após a microinjeção de antalarmina (dose 0,1 μg / 0,1 μL) em comparação ao controle, devido a um aumento do volume corrente. A resposta hipercápnica de animais tratados com o antagonista de CRF1 foi maior em ambas as doses administradas, a dose de 0,05 μg / 0,1 μL provocou um aumento da ventilação em 15 min após a exposição CO2, e essa resposta aumentou ainda mais na dose de 0,1 μg / 0,1 μL em 30 minutos após a exposição CO2 em comparação com animais tratados com veículos, devido a um aumento do volume corrente. Nossos resultados sugerem que os receptores CRF1 no LC exercem um papel inibitório tônico na ventilação e a modulação inibitória na resposta respiratória ao CO2.
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Nicola, Angela Cristina de [UNESP]. "Atividade dos neurônios noradrenérgicos do Locus coeruleus e o conteúdo de GnRH em ratas Wistar acíclicas." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/92094.
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Fundação para o Desenvolvimento da UNESP (FUNDUNESP)
As alterações nos componentes reprodutivos do eixo hipotálamo-hipófise-gônadas em muitas fêmeas de mamíferos determinam a transição gradual de ciclos reprodutivos regulares para ciclos irregulares, com perda de fertilidade. A interação dos neurônios do hormônio liberador de gonadotrofinas (GnRH) e esteróides gonadais representa função chave na neurobiologia do envelhecimento, pois a sobreposição temporal da senescência endócrina e neural está mecanicamente interligada pelas alças de retroalimentação. Estímulos do locus coeruleus (LC) para a área pré-óptica (APO) e eminência mediana são essenciais para a liberação das gonadotrofinas e seus neurônios apresentam receptores para estrógeno e progesterona, sugerindo controle dos esteróides ovarianos. Neste estudo foi avaliado a atividade de células neuronais localizadas em áreas e núcleos envolvidos com o controle de ação dos neurônios GnRH de ratas Wistar no período de transição para a aciclicidade. Para este trabalho foram utilizadas fêmeas Wistar cíclicas (4 meses) e acíclicas (18-20 meses) submetidas à decapitação ou perfusão às 10, 14 e 18 h na fase do diestro. Após serem retirados, os cérebros dos animais decapitados foram congelados e armazenados para posterior determinação do conteúdo de GnRH hipotalâmico e do conteúdo de noradrenalina e dopamina na APO. Os cérebros perfundidos foram cortados seriadamente em secções coronais de 30 μm para a APO e o LC e...
Changes in reproductive components of the hypothalamic-pituitary-gonadal axis in many female mammals determine the gradual transition from regular reproductive cycles to irregular cycles, with loss of fertility. The interaction of neurons of gonadotropin-releasing hormone (GnRH) and gonadal steroids represents key role in the neurobiology of aging, because the temporal overlap of endocrine and neural senescence is mechanically interconnected by feedback loops. Stimulation of the locus coeruleus (LC) for the preoptic area (POA) and median eminence are essential for the release of gonadotropins and their neurons have receptors for estrogen and progesterone, suggesting control of ovarian steroids. Therefore, in this study we evaluated the activity of neuronal cells located in areas and nuclei involved in the control of action of GnRH neurons of female rats during the transition to acyclicity. For this study, we used cyclic female (4 months) and acyclic (18-20 months) rats underwent perfusion or decapitation at 10, 14 and 18 h of diestrus day. The brains from decapitated animals, after removed, were frozen and stored for subsequent determination of the hypothalamic GnRH content and the noradrenaline and dopamine content in the POA. The perfused brains were serially cut into coronal sections of 30 μm to POA and LC and subsequently submitted to immunohistochemical labeling for Fos (FRA) and FRA / TH, respectively. For quantitative analysis of the POA were considered plates containing AVPe being the counting of neurons FRA-ir performed from the insertion of the box with...
FAPESP: 12/14464-6
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Zhang, Xiaoli. "Locus Coeruleus Neurons in Autonomic Regulation of Breathing: Insight from a Mouse Model of Rett Syndrome." Digital Archive @ GSU, 2010. http://digitalarchive.gsu.edu/biology_diss/74.
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Patients with Rett Syndrome (RTT) show severe breathing disorders in addition to other neuropathological features, contributing to the high incidence of sudden unexplained death and abnormal brain development. However, the molecular and cellular mechanisms underlying the breathing disorders are still unknown. Recent studies indicate that the dysfunction of brainstem norepinephrine (NE) systems are closely associated with breathing disorders in RTT patients as well as its mice model, the Mecp2-null (Mecp2─/Y) mice. This as well as the fact the major group of NE-ergic neurons in the locus coeruleus (LC) is CO2 chemosensitive suggests that the breathing disorders in RTT may be related these LC neurons. To test this hypothesis, we took a multidisciplinary approach and systematically studied these neurons using molecular biology, in-vitro brain slices, acutely dissociated neurons, immunocytochemistry, and whole-body plethysmograph. To facilitate the electrophysiological studies, we developed a new strain of transgenic mice with GFP expression selectively in the LC neurons of both WT and Mecp2─/Y mice. Breathing activity of the Mecp2─/Y mice showed selective disruptions in responses to mild hypercapnia. The defect was alleviated with the NE uptake blocker desipramine, suggesting the involvement of NE in central CO2 chemosensitivity. In the LC region, the expressions of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) at both protein and mRNA levels reduced by ~50% in Mecp2─/Y mice. No evidence was found for selective deficiency in TH- or DBH-containing neurons in Mecp2─/Y mice, and no major loss of NE-ergic LC cells were found, indicating that the NE defect is likely to result from deficient expression of biosynthetic enzymes rather than a loss of neurons in the LC. Several intrinsic membrane properties were abnormal in Mecp2─/Y LC neurons in comparison to wild type cells, including stronger inward rectification, shorter time constant, extended action potential duration, smaller amplitude of medium afterhyperpolarization (AHP) and over-expression of fast AHP. These abnormalities seem to be associated with the altered K+ and Na+ currents. Most importantly, Mecp2─/Y LC neurons displayed defective CO2 chemosensitivity in agreement of in vivo CO2 response, likely due to excessive expression of the homomeric Kir4.1 channel. Thus, it seems that the global effect of MeCP2 on the A6 NE system contributes to the impaired systemic CO2 response as well as the breathing irregularities in Mecp2─/Y mice. Such an alteration allowed CO2 to be detected only when hypercapnia became severe, leading to periodical hyper- and hypoventilation. These findings not only provide a novel etiology for the breathing disturbances of Mecp2─/Y mice but also show direct evidence for the first time on a molecular mechanism for the central CO2 chemosensitivity.
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Tadepalli, Sakuntala Jyothirmayee. "Systematic Studies of Kir and TRP Channel mRNAs in the Norepinephrenergic Neurons of the Locus Coeruleus." Digital Archive @ GSU, 2011. http://digitalarchive.gsu.edu/biology_theses/32.
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Neurons in the Locus coeruleus (LC) play an important role in the central CO2 chemosensitivity. However, the molecular mechanisms for neuronal CO2 chemosensitivity remain unclear. To demonstrate the expression of pH/CO2 sensitive ion channels, we screened the inward rectifier K+ channels (Kir) and transient receptor protein (TRP) channels, as parallel studies in this lab suggested that certain Kir and TRP channels are involved in neuronal responses to high levels of CO2. Our results showed that several members of the Kir and TRP channel families were robustly expressed in the LC neurons at the mRNA level. Of particular interest are TRPC5, Kir4.1 and Kir5.1 channels that are all pH-sensitive. The rich expression of various pH-sensitive Kir and TRP channels suggests that these ion channels are likely to play a role in the chemosensitivity of LC neurons.
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Nicola, Angela Cristina de. "Atividade dos neurônios noradrenérgicos do Locus coeruleus e o conteúdo de GnRH em ratas Wistar acíclicas /." Araçatuba, 2013. http://hdl.handle.net/11449/92094.
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Orientador: Rita Cássia Menegati DornellesCo-orientador: Janete Aparecida Anselmo-Franci
Banca: Maristela de Oliveira Poletini
Banca: Jacqueline Nelisis Zanoni
Resumo: As alterações nos componentes reprodutivos do eixo hipotálamo-hipófise-gônadas em muitas fêmeas de mamíferos determinam a transição gradual de ciclos reprodutivos regulares para ciclos irregulares, com perda de fertilidade. A interação dos neurônios do hormônio liberador de gonadotrofinas (GnRH) e esteróides gonadais representa função chave na neurobiologia do envelhecimento, pois a sobreposição temporal da senescência endócrina e neural está mecanicamente interligada pelas alças de retroalimentação. Estímulos do locus coeruleus (LC) para a área pré-óptica (APO) e eminência mediana são essenciais para a liberação das gonadotrofinas e seus neurônios apresentam receptores para estrógeno e progesterona, sugerindo controle dos esteróides ovarianos. Neste estudo foi avaliado a atividade de células neuronais localizadas em áreas e núcleos envolvidos com o controle de ação dos neurônios GnRH de ratas Wistar no período de transição para a aciclicidade. Para este trabalho foram utilizadas fêmeas Wistar cíclicas (4 meses) e acíclicas (18-20 meses) submetidas à decapitação ou perfusão às 10, 14 e 18 h na fase do diestro. Após serem retirados, os cérebros dos animais decapitados foram congelados e armazenados para posterior determinação do conteúdo de GnRH hipotalâmico e do conteúdo de noradrenalina e dopamina na APO. Os cérebros perfundidos foram cortados seriadamente em secções coronais de 30 μm para a APO e o LC e...
Abstract: Changes in reproductive components of the hypothalamic-pituitary-gonadal axis in many female mammals determine the gradual transition from regular reproductive cycles to irregular cycles, with loss of fertility. The interaction of neurons of gonadotropin-releasing hormone (GnRH) and gonadal steroids represents key role in the neurobiology of aging, because the temporal overlap of endocrine and neural senescence is mechanically interconnected by feedback loops. Stimulation of the locus coeruleus (LC) for the preoptic area (POA) and median eminence are essential for the release of gonadotropins and their neurons have receptors for estrogen and progesterone, suggesting control of ovarian steroids. Therefore, in this study we evaluated the activity of neuronal cells located in areas and nuclei involved in the control of action of GnRH neurons of female rats during the transition to acyclicity. For this study, we used cyclic female (4 months) and acyclic (18-20 months) rats underwent perfusion or decapitation at 10, 14 and 18 h of diestrus day. The brains from decapitated animals, after removed, were frozen and stored for subsequent determination of the hypothalamic GnRH content and the noradrenaline and dopamine content in the POA. The perfused brains were serially cut into coronal sections of 30 μm to POA and LC and subsequently submitted to immunohistochemical labeling for Fos (FRA) and FRA / TH, respectively. For quantitative analysis of the POA were considered plates containing AVPe being the counting of neurons FRA-ir performed from the insertion of the box with...
Mestre
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Atmore, Katherine H. "Locus-coeruleus norepinephrine system function in a developmental animal model of schizophrenia: the socially isolated rat." Master's thesis, University of Cape Town, 2017. http://hdl.handle.net/11427/24872.
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Introduction: Schizophrenia is a chronic, debilitating mental disorder characterised by positive, negative and cognitive symptoms. Current treatment regimens fail to adequately address the cognitive and negative symptoms of the disorder. Social isolation rearing (SIR) is a well-established developmental adversity paradigm which is used as an animal model of schizophrenia and usually studied in male rats. Previous SIR studies have found attentional abnormalities in isolated rats in behavioural tests which correspond to the results of studies investigating the cognitive symptoms of schizophrenia in patient trials. Isolated rats also display abnormal social responses which may be of relevance to the negative symptoms of schizophrenia. The primary aim of this study was to build on existing SIR literature by performing behavioural tests in socially isolated rats to address attentional function. Neurochemical investigations were performed on projections of the locus coeruleus norepinephrine system, known to be involved in attentional function, as research on this system is surprisingly sparse. The secondary aim of the study was to address the negative symptoms of schizophrenia using ultrasonic vocalisation recording to investigate the calling behaviour of isolated rats in response to a novel context. The study included both male and female rats so that sex differences could be studied in the context of social isolation. Methodology: Sprague-Dawley rats were weaned at postnatal day (p) 21 and randomly allocated to one of four housing groups; female socialised (n=50), female isolated (n=50), male socialised (n=38) and male isolated (n=38). Socialised animals were housed 4 per cage (single sex) and isolated animals were housed alone. Animals were weighed and cages cleaned weekly as part of a minimal handling protocol required for SIR. After 8 weeks in their housing conditions (p78-82) rats underwent one of two behavioural paradigms: three phase novel object recognition or ultrasonic vocalisation recordings. Between p90-94 animals were rapidly decapitated and the hippocampus and prefrontal cortex were dissected out for use in one of two neurochemical analyses. For in-vitro superfusion experiments the tissue was used immediately to quantify functional release of radioactively-labelled norepinephrine when stimulated with glutamate under varying conditions. Enzyme linked immunosorbent assays (ELISA) and bicinchoninic acid (BCA) protein assays was performed to quantify norepinephrine and glutamate concentrations expressed in relation to the wet weight of the tissue and amount of protein in the tissue. Results: Behavioural and neurochemical changes were induced by the SIR model. Isolated animals were found to respond to novel objects abnormally compared to control animals. During initial exposure to a novel environment in the first phase of the novel object recognition test isolated animals demonstrated hypoactivity. An overall reduction in the fractional release of norepinephrine when stimulated with combinations of glutamate and gamma-aminobutyric acid (GABA) was demonstrated in the hippocampus of isolated rats. Sex differences were evident in a number of experiments. Female rats were found to be hyperactive in the three phases of the novel object recognition test compared to males and also had elevated hippocampal norepinephrine activity as well as an increased concentration of norepinephrine in this area. Male rats on the other hand had an elevated prefrontal cortex norepinephrine activity and concentration. Conclusion: The SIR paradigm is able to induce behavioural and neurochemical changes in both female and male rats. The results of this study reinforce the usefulness of SIR as a model for schizophrenia as the way in which isolated animals responded to novel objects was different to their socialised counterparts. This difference implies an abnormal attentional response which corresponds to the cognitive symptoms described in schizophrenia. Furthermore, the neurochemical experiments performed in this study are the first of their kind and provide preliminary evidence for the GABAergic mechanisms underlying attentional abnormalities associated with SIR. The prevalence of sex differences throughout testing also provides strong evidence for the inclusion of both sexes in future studies to avoid the omission of potentially important findings. Future studies to refine and build on neurochemical analyses in developmental models of schizophrenia, such as SIR will potentially provide a mechanistic understanding of cognitive dysfunction as well as useful translational information for treating the human disorder.
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Zhao, S. "The role of the locus coeruleus noradrenergic system in tracking the statistics of rapid sound sequences." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10048029/.
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The sensory world is full of uncertainty; most perception-relevant statistics are highly dynamic, featuring frequently-changing patterns. Rapid adaptation to the everchanging world requires brain sensitivity to environmental changes and resetting of functional neural networks as needed. Norepinephrine (NE) is proposed to mediate this process by initiating functional resetting (Dayan and Yu, 2006; Sara and Bouret, 2012) via the Locus Coeruleus (LC)-NE system. This doctoral thesis employs pupil diameter measurements – a reliable indicator of NE neural activity in the LC (Aston-Jones and Cohen, 2005; Joshi et al. 2016). Human participants listened to sequences of adjoined 50ms tone-pips (adapted from Barascud et al., 2016) containing transitions from random to regular frequency patterns and vice-versa. Participants were instructed to detect occasionally inserted silent gaps, ensuring attention to the auditory stream, not the transition itself. Although both transitions (regular-to-random and random-to-regular) are clearly detectable behaviourally and evoke strong MEG (Barascud et al., 2016), only violations of regularity (prediction errors) appear to elicit pupil responses. Noteworthily, this response is driven by pattern changes and not merely deviant detection. However, stimuli containing pattern emergences (precision increase) evoke no measurable pupil response; this is not due to pre-transition pupillary saturation, as transitions from random patterns to repeating single tones (random-to-repeating) evoke transient pupil dilation. Only when subjects actively reported changes in button-press did random-to-regular transitions evoke pupil dilations. Investigating the effect of task on evoked pupil responses found no response if subjects were not continuously tracking the sequences, e.g. with attention directed to visual or tactile stimuli. Multiple self-replications of these findings provide robust evidence that NE release acts as an automatic switch, resetting the brain’s internal model of the sensory environment and demonstrating that the unexpected uncertainty signalling process operates over much faster timescales than previously known, implicating NE in the fundamental bases of perception.
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Asker, Mohammed. "Real-time measurement of locus coeruleus (LC) activity during eating and mild stress with fiber photometry." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-17138.
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Stress has been always associated with a deviating than normal feeding behavior. Both over-eating and under-eating accompanied by altered food choice towards palatable food have been reported in response to stress. The neuronal pathways that link stress with eating are still unclear. Locus Coeruleus (LC) is the main endogenous norepinephrine (NE) secreting nucleus. It lies in the center of the stress response mediating arousal state. LC-NE nucleus with its widespread innervations throughout the brain can modulate brain mechanisms linked with motivation towards food. In this study, the aim was to study the activity of NE neurons in the LC in relation to stress and food intake. The hypothesis was that NE neurons are activated by mild stressors and that this activity drives food intake. Because the association between LC activity and food intake is observational by nature, it is not expected to demonstrate a causal link but to show findings consistent with this hypothesis. Another aim was to standardize the photometry measurements and an analysis paradigm. In response to a stressor, animals showed freezing behavior, with photometry recordings displaying a significant reduction in Ca+2 signals right after the distressing stimulus. When a stressor preceded food intake, LC-NE activity significantly decreased right after the first meal the effect that did not last to the second meal with no difference between chow and palatable food. These results highlight the involvement of LC-NE in modulating feeding behavior by integrating environmental cues and internal needs. Future investigations of distinct, projection-defined, LC-NE sub-populations may reveal more specific food and stress interactions.
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Charléty, P. J. "Interaction entre sérotonine et acides aminés excitateurs dans le noyau du locus coeruleus : approche électrophysiologique in vivo chez le rat." Lyon 1, 1993. http://www.theses.fr/1993LYO1T024.
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Lanfumey, Laurence. "Plasticite du systeme nerveux central au cours du developpement : effets de la lesion neonatale du locus coeruleus." Paris 6, 1988. http://www.theses.fr/1988PA066680.
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Lanfumey, Laurence. "Plasticité du système nerveux central au cours du développement effets de la lésion néonatale du Locus coeruleus /." Grenoble 2 : ANRT, 1988. http://catalogue.bnf.fr/ark:/12148/cb37614930z.
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Ludwig, Felix [Verfasser]. "Locus coeruleus modulates locomotor activity via the medial septum and the diagonal band of Broca / Felix Ludwig." Bonn : Universitäts- und Landesbibliothek Bonn, 2020. http://d-nb.info/1221669052/34.
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Baufreton, Jérôme. "Transmission GABAergique-Régulation dopaminergique : étude in vitro dans deux modèles : le noyau sous-thalamique et le locus coeruleus." Bordeaux 2, 2002. http://www.theses.fr/2002BOR28949.
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Le GABA est le principal neurotransmetteur inhibiteur du système nerveux central. De nombreux facteurs influencent la transmission GABAergique rapide. Notre travail a porté sur l'un d'entre eux : la composition en sous-unités des récepteurs. La sous-unité [epsilon], clonée dans notre laboratoire, confère à des récepteurs GABA A recombinants une insensibilité au flunitrazepam, une benzodiazépine typique. L'expression d'[epsilon] dans le noyau sous-thalamique (NST) étant controversée, nous avons déterminé le profil pharmacologique des récepteurs GABA A natifs du NST dans des tranches de cerveau de rat. Nous avons conclu qu'[epsilon] n'est pas exprimée dans le NST. La cartographie complète de l'expression de la sous-unité [epsilon] dans le cerveau de rat a ensuite été établie. Elle indiquait sa présence dans le locus coeruleus. Nous montrons que les courants post-synaptiques miniatures du locus coeruleus, bien que potentialisés par le flunitrazepam, ont des cinétiques différentes du NST. L'origine de la spécificité de la transmission GABAergique du locus coeruleus reste à établir. La dopamine contrôle la transmission GABAergique, mais aussi l'exitabilité des neurones : l'activation des récepteurs dopaminergiques de la famille D1 renforce l'activité "en bouffée" des neurones du NST, qu'elle soit spontanée ou évoquée. Cet effet est dû à la potentialisation d'une conductance calcique nifédipine- et calciceptine sensible. Il passe par une protéine G et une protéine kinase A. Présent chez la souris, il persiste chez des souris transgéniques aux récepteurs D1 invalidés. Nous suggérons, en nous appuyant sur nos expériences de RT-PCR sur cellule unique, que les neurones du NST expriment seulement des récepteurs D5, et pas de récepteurs D1. L'action de la dopamine sur la transmission synaptique GABAergique via les récepteurs D5 reste à étudier.
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Cerpa, Gilvonio Juan Carlos. "Cortex préfrontal et flexibilité comportementale : implication de la noradrénaline." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0367.
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La survie d’un organisme nécessite qu’il soit capable de prendre des décisions adaptées dans un environnement changeant. Ces décisions dépendent de multiples processus cognitifs qui ont pu être étudiés par l’intermédiaire des apprentissages associatifs. Ainsi, le contrôle de l’action repose sur des processus distribués au sein de larges circuits cérébraux impliquant notamment les régions préfrontales. Ces fonctions du cortex préfrontal sont largement influencées par l’action de neuromodulateurs, parmi lesquels la noradrénaline, qui pourrait jouer un rôle essentiel dans la flexibilité comportementale. Mon travail de thèse a donc cherché à déterminer l’implication de l’innervation noradrénergique du cortex préfrontal dans l’adaptation à des changements des conséquences de l’action. Une première partie a consisté à étudier l’organisation de l’innervation noradrénergique au sein de différentes aires préfrontales par des méthodes de quantification automatisée. Dans une deuxième partie, nous avons utilisé un protocole instrumental nécessitant un apprentissage flexible des relations causales entre actions et conséquences. A l’aide de ce protocole et de toxines induisant une déplétion noradrénergique, nous avons démontré l’implication de la noradrénaline au sein d’une région du cortex préfrontal, le cortex orbitofrontal, pour la flexibilité comportementale nécessaire au contrôle de l’action, en particulier pour prendre en compte des changements dans l’identité et la valeur des récompenses associées à cette action. Une comparaison avec le cortex préfrontal médian d’une part, et avec le rôle de l’innervation dopaminergique d’autre part, suggère que le rôle de la noradrénaline est spécifique de la région et de l’espèce neurochimique. Dans une troisième partie, nous avons développé plusieurs approches pharmacogénétiques visant à préciser les phases de l’apprentissage impliquant la modulation noradrénergique, et observé certaines limites de ces approches. Ces travaux confirment l’importance de l’action neuromodulatrice sur les fonctions préfrontales et surtout étendent nos connaissances des circuits cérébraux impliqués dans le contrôle de l’action permettant l’adaptation à un environnement changeantAn organism depends for its survival on the ability to take adaptive decisions in an ever-changing environment. These decisions involve several cognitive processes that can be revealed by the study of associative learning processes. Thus, action control has been found to rely on processes that distribute across a network of cerebral structures including prefrontal regions. Prefrontal functions are largely influenced by neuromodulators such as noradrenaline, which is thought to be involved in behavioural flexibility. My Ph.D. project therefore aimed at clarifying the role of noradrenergic modulation of prefrontal cortex regions in adapting a subject’s behaviour to changes in action consequences. In the first chapter, we studied the organization of noradrenergic innervation in the various prefrontal areas, by means of an automated quantification method. In the second chapter, we applied a behavioural protocol requiring flexible learning of the causal relationships between actions and their outcomes. Using this protocol and neurotoxins to deplete prefrontal regions from noradrenergic innervation, we showed that noradrenaline in a specific area, the orbitofrontal cortex, was necessary to action control, in particular to mediate changes in the identity and value of expected outcomes. Comparing this contribution to the role of medial prefrontal cortex on one hand, and of dopaminergic modulation on the other hand, suggests that the role of noradrenergic neuromodulation is both region- and mediator-specific. In the third chapter, we developed a series of chemogenetic approaches to identify the temporal involvement of noradrenaline in the various phases of the task, and we identified some of the limits of these approaches. This work confirms the importance of neuromodulation in prefrontal cortical function and furthers our understanding of cerebral circuits involved in action control and adaptation to a changing environment
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Poisson, Alice. "Plasticité anormale et maladie de Parkinson : de l'akinésie à l'hyperkinésie." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10261/document.
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Nous avons pris le parti pour cette thèse d'étudier en Imagerie par Résonance Magnétique fonctionnelle deux éléments sémiologiques de la maladie de Parkinson : les mouvements en miroir et l'akinésie. Ces deux phénomènes reflètent une plasticité cérébrale anormale dans cette maladie. Notre première expérience révèle que les mouvements en miroir chez les patients parkinsoniens sont contemporains 1/ d'un défaut d'inhibition, notamment réactive. 2/ de nombreuses hyperactivations, pouvant refléter soit un recrutement compensateur soit une perte délétère de la sélectivité de l'activation corticale. La deuxième expérience s'intéresse à une autre forme d'inhibition, l'inhibition proactive. Nos résultats révèlent que les structures participant au contrôle moteur proactif et notamment le précuneus et les cortex cingulaires postérieur et antérieur sont modulés par le système noradrénergiques chez le sujet sain. Dans une troisième expérience nous avons appliqué ce protocole expérimental à des sujets parkinsoniens. La comparaison avec les données issues de la première expérience révèlent 1/ que les sujets parkinsoniens ont une implémentation anormale du réseau d'inhibition proactive avec une difficulté à se placer en condition de déverrouillage moteur. Ce phénomène pourrait allonger le temps de réaction et participer à l'akinésie. 2/ que l'administration de clonidine renforce encore ce phénomène, en agissant sur les structures antérieures du réseau d'inhibition proactive (cortex cingulaire antérieur et cortex préfrontal dorsomédial). Tous ensembles ces résultats suggèrent une plasticité anormale dans la maladie de Parkinson sousjacente aux mouvements en miroir et à l'akinésie. Celle-ci se traduit 1/ par des défauts d'inhibition, notamment réactive, favorisant l'apparition de mouvements parasites, les mouvements en miroir, 2/ par un renforcement pathologique de l'inhibition proactive qui pourrait participer à l'allongement du temps de réaction et à l'akinésie. La découverte d'une modulation noradrénergique de ce réseau ouvre des portes thérapeutiques nouvelles dans l akinésie parkinsonienne mais également dans l'impulsivité dont certains composants, notamment moteur, semblent être liés à l'inhibition proactiveMirror movements and akinesia can be both found during Parkinson’s disease. Although very different, they may both reflect an abnormal cerebral plasticity during the disease and the perturbation of the motor inhibitory control. This work reveals that mirror movements are linked to a1/ disruption of the reactive inhibitory control and 2/ to the overactivation of numerous cortical areas. The latter could be the result of a compensatory recruitment aiming at improving the movement. But they could as well reflect a deleterious loss of cerebral activation specificity during Parkinson’s disease. The second experience shows that in healthy subject, the proactive inhibitory control is underpinned by the noradrenergic system. Last but not least the third part of this work reveals an abnormal implementation of the proactive inhibitory control in Parkinson’s disease and suggests its involvement in akinesia. Brought together these results suggest that an abnormal plasticity phenomenon underlies the mirror movements and the akinesia in Parkinson’s disease. More precisely, we observed a default of the reactive inhibitory control associated to mirror movements in Parkinson’s disease and an excess of proactive inhibitory control that seems to be linked to akinesia. The finding of an adrenergic modulation of the proactive inhibitory control opens the fields for the development of noradrenergic therapeutics in akinesia
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Holm, Pontus. "Survival and differentiation of central noradrenergic neurons /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-277-9.
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Charifi, Chademan. "Role des structures telencephaliques innervees par le systeme noradrenergique du locus coeruleus dans le controle des mecanismes du rebond apres privation de sommeil chez le rat (doctorat neurosciences)." Lyon 1, 2001. http://www.theses.fr/2001LYO1T077.
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Mitchell, Jacqueline Clare. "The role of the locus coeruleus suppression of the gonadotrophin releasing hormone pulse generator in the female rat." Thesis, King's College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.411046.
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Cazuza, Rafael Alves. "Possível envolvimento do monóxido de carbono na modulação do comportamento emocional em ratos: o papel do locus coeruleus." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/59/59134/tde-19042017-123841/.
Full textAbstract:
O gás monóxido de carbono (CO) possui diversas funções no sistema nervoso central (SNC) funcionando como neuromodulador, como por exemplo da regulação da temperatura corporal, da nocicepção e mais recentemente, do comportamento emocional. Este neuromodulador gasoso é produzido pela ação da enzima heme oxigenase (HO), a qual é encontrada em diferentes áreas do SNC. Com destaque, esta enzima tem alta expressão no locus coeruleus (LC), o que sugere o envolvimento do CO na modulação de funções desempenhadas por esta estrutura. O LC localiza-se na ponte, sendo a maior origem da inervação noradrenérgica do SNC. Esta estrutura tem participação ativa na modulação das respostas relacionadas ao estresse, em particular, na modulação do comportamento emocional, desde que integra o Sistema de Inibição Comportamental (SIC), o qual inclui ainda o sistema septo-hipocampal e os núcleos da rafe. O SIC é responsável por comandar respostas defensivas de avaliação de risco, alerta e atenção, as quais podem ser eliciadas pela ansiedade. Dentro desta perspectiva, o presente estudo teve como objetivo avaliar se a ativação sistêmica da via HO-CO pode modular o comportamento emocional de ratos, e se há participação do LC. Assim, este trabalho avaliou se o tratamento sistêmico via intraperitoneal (i.p.) agudo (3 h antes) ou crônico (10 dias/2 vezes ao dia) com um liberador de monóxido de carbono (CORM-2), ou com indutor da enzima HO (CoPP), altera as respostas comportamentais no teste do labirinto em cruz elevado (LCE) e no teste claro-escuro (TCE) em ratos, bem como a expressão da enzima HO no LC. Em uma segunda etapa foi avaliado se a administração aguda de CORM-2 ou CoPP altera o comportamento avaliado no LCE e no TCE de ratos submetidos ao estresse crônico variado (ECV) por 10 dias. Os resultados mostraram que o CO induzido pela administração aguda ou crônica de CORM-2 ou CoPP possui efeito ansiolítico. Ainda, o tratamento com CORM-2 ou CoPP aumentou a expressão da enzima HO-1 em células localizadas no LC, sem alterar a imunorreatividade à enzima HO-2. Considerando os grupos submetidos ao estresse ECV, nem a ativação da via HO-CO ou o ECV apresentaram efeitos significativos nos comportamentos avaliados nos testes LCE e TCE. Os resultados do presente estudo sugerem que o tratamento sistêmico com drogas que modulam a liberação de CO possui claro efeito ansiolítico. Assim, é possível que o CO possa ser uma droga com potencial terapêutico para o tratamento de desordens neuropsiquiátricas.The carbon monoxide gas (CO) has several functions in the central nervous system acting as a neuromodulator, such as in the body temperature regulation, nociception and more recently, in the emotional behavior modulation. This gas is produced by the action of the heme oxigenase enzyme (HO), which is found in different areas of the central nervous system (CNS). It is important to note that this enzyme has high expression in the locus coeruleus (LC), suggesting the involvement of CO in the modulation functions performed by this midbrain structure. LC is located in the pons, being the source of majority of the noradrenergic innervation of the CNS. This structure is intimately involved in the stress modulation responses, particularly in the emotional behavior regulation, since it integrates the Behavioral Inhibition System (BIS), which also includes septum-hippocampal system and raphe nucleus. The BIS is responsible for defensive responses like the risk assessment and alertness trigged by anxiety. Within this perspective, the present study was designed to evaluate whether the systemic HO-CO pathway can modulate emotional behavior of rats, and if the HO enzyme of the neurons located into LC is involved in this response. Thus, this study evaluated whether the acute systemic i.p. treatment (3 hours before) or chronic (10 days / 2 times a day) with a carbon monoxide releaser (CORM-2) or inducer of heme enzyme oxygenase (CoPP), is able to alter the behavioral responses in the elevated plus maze (EPM) and in the light-dark box test (LDB) in rats, and the HO enzyme expression in the LC. Furthermore, the effect of the acute administration of CORM-2 or CoPP was evaluated in the emotional behavior assessed in the EPM and LDB by rats submitted to unpredictable chronic stress (during 10 days). The results showed that the CO induced by acute or chronic administration of CORM-2 or CoPP has an anxiolytic-like effect. Furthermore, treatment with CORM-2 or CoPP promoted an increase of HO-1 enzyme expression in cells located in the LC without altering the immunoreactivity of HO-2 enzyme. Still, considering the rats subjected to stress UCS neither the activation of HO-CO pathway nor the UCS protocol altered the emotional behavior evaluated in the EPM and LDB tests. The results of this study suggest that systemic treatment with drugs that modulate the CO release has anxiolytic effect. Thus, it is possible that CO can be a potential drug therapeutic target for neuropsychiatric disorders.
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Ordway, Gregory A., Attila Szebeni, Michelle M. Duffourc, and Katalin Szebeni. "Laser Capture Microdissection and RT- PCR Analyses of Specific Cell Types in Locus Coeruleus From Postmortem Human Brain." Digital Commons @ East Tennessee State University, 2007. https://dc.etsu.edu/etsu-works/8624.
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Morphological studies have shown pathology of neurons and glia in many brain disorders, including psychiatric disorders such as major depression. However, most biochemical characterizations of postmortem human brain tissue have not made a distinction between neurons and glia. Laser capture microdissection (LCM) to isolate specific cell types has the potential to advance our understanding of human brain pathologies. Here, RT-PCR was used to evaluate the utility of LCM in the capture of noradrenergic neurons, astrocytes and oligodendrocytes from the locus coeruleus (LC) of postmortem human brain. The 3 LC cell types were individually identified using modifications of established histological and morphological methods. LCM settings were optimized for each cell type and captured cell bodies were those having no nearby cell body of a different phenotype. LC neurons (200), astrocytes (500), and oligodendrocytes (500) were captured within the LC from 3 postmortem brains. RNA was isolated, reversed transcribed, and markers for neurons (tyrosine hydroxylase [TH], dopamine beta-hydroxylase [DBH]), astrocytes (glial fibrillary acidic protein [GFAP]), and oligodendrocytes (myelin oligodendrocyte glycoprotein [MOG]), along with 3 references (actin, GAPDH, ubiquitin C) were PCR amplified and quantified by standardized end-point PCR. RNA quality as assessed by RIN was not altered by LCM as compared to RNA isolated from homogenized tissue. TH gene expression was found only in neurons in 2 of the 3 brains. DBH gene expression was ~5-fold greater in neurons than in astrocytes and oligodendrocytes. GFAP gene expression in astrocytes was 7- and 5-fold greater than that in neurons and oligodendrocytes, respectively. MOG gene expression was only detected in oligodendrocytes. Different expression ratios of marker genes between neurons and glia suggest that simple cross contamination of mRNA is unlikely. Glial cells may contain DBH mRNA. Alternatively, DBH, but not TH, mRNA may occur in neuronal dendrites or axons in close association with glial cells that become captured with glia during LCM. GFAP may be expressed in low levels in neurons and oligodendrocytes, or alternatively, GFAP mRNA may be located in astrocytic processes in close association with neuronal and oligodendrocyte cell bodies. Use of a single marker to identify a cell type may be insufficient; other cell types for comparison or additional markers may be required. Multiple well-characterized markers can be used to evaluate clarity of cell capture for each sample. With due regard for specific limitations, LCM can be used to evaluate the molecular pathology of specific cell types in postmortem human brain.