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1
Williams, Gareth, Joanne A. Harrold, and David J. Cutler. "The hypothalamus and the regulation of energy homeostasis: lifting the lid on a black box." Proceedings of the Nutrition Society 59, no. 3 (2000): 385–96. http://dx.doi.org/10.1017/s0029665100000434.
Testo completoAbstract (sommario):
The hypothalamus is the focus of many peripheral signals and neural pathways that control energy homeostasis and body weight. Emphasis has moved away from anatomical concepts of ‘feeding’ and ‘satiety’ centres to the specific neurotransmitters that modulate feeding behaviour and energy expenditure. We have chosen three examples to illustrate the physiological roles of hypothalamic neurotransmitters and their potential as targets for the development of new drugs to treat obesity and other nutritional disorders. Neuropeptide Y (NPY) is expressed by neurones of the hypothalamic arcuate nucleus (ARC) that project to important appetite-regulating nuclei, including the paraventricular nucleus (PVN). NPY injected into the PVN is the most potent central appetite stimulant known, and also inhibits thermogenesis; repeated administration rapidly induces obesity. The ARC NPY neurones are stimulated by starvation, probably mediated by falls in circulating leptin and insulin (which both inhibit these neurones), and contribute to the increased hunger in this and other conditions of energy deficit. They therefore act homeostatically to correct negative energy balance. ARC NPY neurones also mediate hyperphagia and obesity in the ob/ob and db/db mice and fa/fa rat, in which leptin inhibition is lost through mutations affecting leptin or its receptor. Antagonists of the Y5 receptor (currently thought to be the NPY ‘feeding’ receptor) have anti-obesity effects. Melanocortin-4 receptors (MC4-R) are expressed in various hypothalamic regions, including the ventromedial nucleus and ARC. Activation of MC4-R by agonists such as α-melanocyte-stimulating hormone (a cleavage product of pro-opiomelanocortin which is expressed in ARC neurones) inhibits feeding and causes weight loss. Conversely, MC4-R antagonists such as ‘agouti’ protein and agouti gene-related peptide (AGRP) stimulate feeding and cause obesity. Ectopic expression of agouti in the hypothalamus leads to obesity in the AVY mouse, while AGRP is co-expressed by NPY neurones in the ARC. Synthetic MC4-R agonists may ultimately find use as anti-obesity drugs in human subjects Orexins-A and -B, derived from prepro-orexin, are expressed in specific neurones of the lateral hypothalamic area (LHA). Orexin-A injected centrally stimulates eating and prepro-orexin mRNA is up regulated by fasting and hypoglycaemia. The LHA is important in receiving sensory signals from the gut and liver, and in sensing glucose, and orexin neurones may be involved in stimulating feeding in response to falls in plasma glucose.
2
Adams, Eric F., Maria S. Venetikou, Christine A. Woods, S. Lacoumenta, and J. M. Burrin. "Neuropeptide Y directly inhibits growth hormone secretion by human pituitary somatotropic tumours." Acta Endocrinologica 115, no. 1 (1987): 149–54. http://dx.doi.org/10.1530/acta.0.1150149.
Testo completoAbstract (sommario):
Abstract. Neuropeptide Y (NPY) is a 36 amino acid peptide, widely distributed throughout the brain and is found in hypothalamic neurones. This latter finding suggests that NPY may possess a hypophysiotropic function. A number of studies have demonstrated effects of NPY on LH and GH secretion by rat pituitary cells. We report here the results of experiments investigating the effects of NPY on GH secretion by tumorous human somatotropic pituitary cells in culture. NPY (0.25–25 nmol/l) inhibited GH secretion by 20–53%, the maximal effect depending upon the tumour studied. The potency of NPY was less than that of somatostatin (SRIH). The stimulatory effects of growth hormone releasing factor (GHRH) and theophylline were reduced by NPY, but NPY did not modify the inhibitory effect of SRIH on GH secretion. It is concluded that NPY may be involved in the control of GH secretion, at least by tumorous human pituitary somatotropes.
3
Gładysz, A., P. Krejci, J. Simůnek, and J. Polkowska. "Effects of central infusions of neuropeptide Y on the somatotropic axis in sheep fed on two levels of protein." Acta Neurobiologiae Experimentalis 61, no. 4 (2001): 255–66. http://dx.doi.org/10.55782/ane-2001-1401.
Testo completoAbstract (sommario):
Effects of infusions of neuropeptide Y (NPY) into 3rd ventricle of growing sheep fed on diets containing restricted (R) or elevated (E) levels of protein on the immunoreactive (ir) somatostatin neurones, ir somatotrophs, growth hormone (GH) concentration in the blood plasma were studied. The long-term restriction of protein in the diet elicited: enhancing irSS content in periventricular perikarya; diminishing irSS stores in the median eminence and elevating the number ir somatotrophs and content of irGH. NPY infusions enhanced the content of irSS in perikarya in sheep fed on E diet and diminished the number of ir somatotrophs and content of irGH of sheep fed on R diet. The R diet as well as NPY infusions caused an increase in GH mean concentrations in the blood plasma. Obtained results suggest that timulatory effect of restricted feeding and/or NPY action on GH secretion can be due to attenuated SS output. Since dietary restrictions and exogenous NPY have similar influence on the activation of GH secretion, we suggest that NPY could be a neuromodulatory link between nutritional cues and somatotropic axis in sheep.
4
Sienkiewicz, W., A. Chrószcz, A. Dudek, M. Janeczek, and J. Kaleczyc. "Caudal mesenteric ganglion in the sheep – macroanatomical and immunohistochemical study." Polish Journal of Veterinary Sciences 18, no. 2 (2015): 379–89. http://dx.doi.org/10.1515/pjvs-2015-0049.
Testo completoAbstract (sommario):
Abstract The caudal mesenteric ganglion (CaMG) is a prevetrebral ganglion which provides innervation to a number of organs in the abdominal and pelvic cavity. The morphology of CaMG and the chemical coding of neurones in this ganglion have been described in humans and many animal species, but data on this topic in the sheep are entirely lacking. This prompted us to undertake a study to determine the localization and morphology of sheep CaMG as well as immunohistochemical properties of its neurons. The study was carried out on 8 adult sheep, weighing from 40 to 60 kg each. The sheep were deeply anaesthetised and transcardially perfused with 4% paraformaldehyde. CaMG-s were exposed and their location was determined. Macroanatomical observations have revealed that the ovine CaMG is located at the level of last two lumbar (L5 or L6) and the first sacral (S1) vertebrae. The ganglion represents an unpaired structure composed of several, sequentially arranged aggregates of neurons. Immunohistochemical investigations revealed that nearly all (99.5%) the neurons were DβH-IR and were richly supplied by VACHT-IR nerve terminals forming „basket-like” structures around the perikarya. VACHT-IR neurones were not determined. Many neurons (55%) contained immunoreactivity to NPY, some of them (10%) stained for Met-ENK and solitary nerve cells were GAL-positive. CGRP-IR nerve fibres were numerous and a large number of them simultaneously expressed immunoreactivity to SP. Single, weakly stained neurones were SP-IR and only very few nerve cells weakly stained for VIP.
5
Károly, Norbert, Endre Dobó, and András Mihály. "Comparative immunohistochemical study of the effects of pilocarpine on the mossy cells, mossy fibres and inhibitory neurones in murine dentate gyrus." Acta Neurobiologiae Experimentalis 75, no. 2 (2015): 220–37. http://dx.doi.org/10.55782/ane-2015-2030.
Testo completoAbstract (sommario):
Treatment with pilocarpine (PILO) induces variable degrees of loss of mossy cells (MCs) and mossy fibre (MF) sprouting in rodents, the relationships of which have not been examined in individual animals. Our aim was to test whether the loss of MCs and MF sprouting are coupled processes in PILO-treated rodents. Animals which exhibited intense PILO-induced convulsions for at least 30 min were used in this study. After a 2-month survival period, the incidence of epileptic seizures was checked individually by neuropeptide-Y (NPY) immunohistochemistry, and the numbers of MCs were counted by means of immunohistochemistry, for calretinin (CR) in mice and calcitonin gene-related peptide (CGRP) in rats. MF sprouting was checked by using Timm’s silver-sulphide method for zinc. In our comparative studies, NPY immunohistochemistry resulted in more positive animals than on zinc staining. The CR immunoreactivity remained unchanged even in those mice that displayed MF sprouting and greatly increased NPY immunoreactivity. CR immunoreactivity was also verified after transection of the fornix to exclude the extrahippocampal source of this peptide. However, the CGRP immunoreactivity was severely reduced in those rats that exhibited simultaneous increases in zinc content and NPY immunoreactivity in the supragranular layer and stratum lucidum. Our findings suggest that the MCs survive PILO treatment in mice, but not in rats. There is direct evidence of a close relationship between the loss of MCs and MF sprouting in rats, but not in mice. Thus, similar PILO seizures may result from different changes in the neuronal circuits of rodents.
6
Chan, Y. Y., D. K. Clifton, and R. A. Steiner. "Role of NPY Neurones in GH-Dependent Feedback Signalling to the Brain." Hormone Research 45, no. 1 (1996): 12–14. http://dx.doi.org/10.1159/000184820.
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Joly, A., R. Denis, J. Castel, R. Palmiter, C. Magnan, and S. Luquet. "O35 Rôle des Neurones NPY/AgRP dans le contrôle de la balance énergétique." Diabetes & Metabolism 36 (March 2010): A10. http://dx.doi.org/10.1016/s1262-3636(10)70039-2.
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Brooks, P. A., J. S. Kelly, J. M. Allen, D. A. S. Smith, and T. W. Stone. "Direct excitatory effects of neuropeptide Y (NPY) on rat hippocampal neurones in vitro." Brain Research 408, no. 1-2 (1987): 295–98. http://dx.doi.org/10.1016/0006-8993(87)90391-x.
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le Roux, C. W., and S. R. Bloom. "Peptide YY, appetite and food intake." Proceedings of the Nutrition Society 64, no. 2 (2005): 213–16. http://dx.doi.org/10.1079/pns2005427.
Testo completoAbstract (sommario):
Obesity is taking on pandemic proportions. The laws of thermodynamics, however, remain unchanged, as energy will be stored if less energy is expended than consumed; the storage is usually in the form of adipose tissue. Several neural, humeral and psychological factors control the complex process known as appetite. Recently, a close evolutionary relationship between the gut and brain has become apparent. The gut hormones regulate important gastrointestinal functions such as motility, secretion, absorption, provide feedback to the central nervous system on availability of nutrients and may play a part in regulating food intake. Peptide YY (PYY) is a thirty-six amino acid peptide related to neuropeptide Y (NPY) and is co-secreted with glucagon-like peptide 1. Produced by the intestinal L-cells, the highest tissue concentrations of PYY are found in distal segments of the gastrointestinal tract, although it is present throughout the gut. Following food intake PYY is released into the circulation. PYY concentrations are proportional to meal energy content and peak plasma levels appear postprandially after 1 h. PYY3-36 is a major form of PYY in both the gut mucosal endocrine cells and the circulation. Peripheral administration of PYY3-36 inhibits food intake for several hours in both rodents and man. The binding of PYY3-36 to the Y2 receptor leads to an inhibition of the NPY neurones and a possible reciprocal stimulation of the pro-opiomelanocortin neurones. Thus, PYY3-36 appears to control food intake by providing a powerful feedback on the hypothalamic circuits. The effect on food intake has been demonstrated at physiological concentrations and, therefore, PYY3-36 may be important in the everyday regulation of food intake.
10
Håkansson, Marie-Louise, Anna-Lena Hulting, and Björn Meister. "Expression of leptin receptor mRNA in the hypothalamic arcuate nucleus - relationship with NPY neurones." NeuroReport 7, no. 18 (1996): 3087–92. http://dx.doi.org/10.1097/00001756-199611250-00059.
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Fergani, C., J. E. Routly, D. N. Jones, L. C. Pickavance, R. F. Smith, and H. Dobson. "KNDy neurone activation prior to the LH surge of the ewe is disrupted by LPS." Reproduction 154, no. 3 (2017): 281–92. http://dx.doi.org/10.1530/rep-17-0191.
Testo completoAbstract (sommario):
In the ewe, steroid hormones act on the hypothalamic arcuate nucleus (ARC) to initiate the GnRH/LH surge. Within the ARC, steroid signal transduction may be mediated by estrogen receptive dopamine-, β-endorphin- or neuropeptide Y (NPY)-expressing cells, as well as those co-localising kisspeptin, neurokinin B (NKB) and dynorphin (termed KNDy). We investigated the time during the follicular phase when these cells become activated (i.e., co-localise c-Fos) relative to the timing of the LH surge onset and may therefore be involved in the surge generating mechanism. Furthermore, we aimed to elucidate whether these activation patterns are altered after lipopolysaccharide (LPS) administration, which is known to inhibit the LH surge. Follicular phases of ewes were synchronised by progesterone withdrawal and blood samples were collected every 2 h. Hypothalamic tissue was retrieved at various times during the follicular phase with or without the administration of LPS (100 ng/kg). The percentage of activated dopamine cells decreased before the onset of sexual behaviour, whereas activation of β-endorphin decreased and NPY activation tended to increase during the LH surge. These patterns were not disturbed by LPS administration. Maximal co-expression of c-Fos in dynorphin immunoreactive neurons was observed earlier during the follicular phase, compared to kisspeptin and NKB, which were maximally activated during the surge. This indicates a distinct role for ARC dynorphin in the LH surge generation mechanism. Acute LPS decreased the percentage of activated dynorphin and kisspeptin immunoreactive cells. Thus, in the ovary-intact ewe, KNDy neurones are activated prior to the LH surge onset and this pattern is inhibited by the administration of LPS.
12
Denis, R. G. P., C. Bing, S. Brocklehurst, J. A. Harrold, R. G. Vernon, and G. Williams. "Diurnal changes in hypothalamic neuropeptide and SOCS-3 expression: effects of lactation and relationship with serum leptin and food intake." Journal of Endocrinology 183, no. 1 (2004): 173–81. http://dx.doi.org/10.1677/joe.1.05659.
Testo completoAbstract (sommario):
Rats normally eat about 85% of their food at night. Lactation increases food intake 3- to 4-fold, but the diurnal pattern of food intake persists. The mechanisms responsible for the diurnal and lactation-induced changes in food intake are still unresolved, hence we have further investigated the possible roles of serum leptin and hypothalamic expression of neuropeptide Y (NPY), agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) in rats. Suppressor of cytokine signalling-3 (SOCS-3) acts as a feedback inhibitor of leptin signalling in the hypothalamus, hence changes in expression of SOCS-3 were also investigated. Changes in expression of NPY, AgRP or POMC alone could not account for the diurnal changes in intake and their alteration by lactation. However, there were increased AgRP mRNA:POMC mRNA ratios at night and also during lactation, which were very similar to estimated changes in food intake. Such changes in expression may result in dominance of the orexigenic AgRP peptide over the appetite-suppressing POMC-derived peptides, and so could contribute to the hyperphagia in these states. Diurnal and lactation-related changes in the AgRP mRNA:POMC mRNA ratio and food intake are not due to changes in leptin alone. However, hypoleptinaemia, possibly through increased expression of NPY, may contribute to the hyperphagia of lactation. In the dark, expression of SOCS-3 was decreased in non-lactating rats; lactation decreased SOCS-3 expression in both light and dark phases. However, such changes are likely to enhance the ability of leptin-responsive neurones to transmit the leptin signal, and so are unlikely to contribute to either the nocturnal increase in appetite or the hyperphagia of lactation.
13
Satoh, N., S. Miyajima, H. Imaishi, S. Iwanaga, and M. Yakushiji. "Calcitonin gene-related peptide (CGRP)-and neuropeptide Y (NPY)neurones in the human umbilical cord." Placenta 19, no. 7 (1998): A40. http://dx.doi.org/10.1016/s0143-4004(98)91200-0.
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Browning and Lees. "Inhibitory effects of NPY on ganglionic transmission in myenteric neurones of the guinea-pig descending colon." Neurogastroenterology and Motility 12, no. 1 (2000): 33–41. http://dx.doi.org/10.1046/j.1365-2982.2000.00178.x.
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Joly, A., R. Denis, J. Castel, C. Cansell, C. Magnan, and S. Luquet. "035 Implication des neurones NPY/AgRP dans le contrôle de la partition des flux énergétiques en périphérie." Diabetes & Metabolism 37, no. 1 (2011): A9. http://dx.doi.org/10.1016/s1262-3636(11)70523-7.
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Mason, R., D. Harland, and B. Rusak. "The electrophysiological effects of neuropeptide-Y (NPY) and arginine-vasopressin (AVP) on rat and hamster suprachiasmatic neurones." Regulatory Peptides 26, no. 1 (1989): 81. http://dx.doi.org/10.1016/0167-0115(89)90157-2.
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Bing, Chen, Peter King, Lucy Pickavance, et al. "The effect of moxonidine on feeding and body fat in obese Zucker rats: role of hypothalamic NPY neurones." British Journal of Pharmacology 127, no. 1 (1999): 35–42. http://dx.doi.org/10.1038/sj.bjp.0702494.
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Pearson, G. T., M. J. Gray, and G. M. Lees. "Morphological and electrophysiological characteristics of neuropeptide Y (NPY)-immunoreactive neurones of the submucous plexus of guinea-pig ileum." Regulatory Peptides 15, no. 2 (1986): 188. http://dx.doi.org/10.1016/0167-0115(86)90132-1.
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Kerekes, Nóra, Marc Landry, Karin Lundmark, and Tomas Hökfelt. "Effect of NGF, BDNF, bFGF, aFGF and cell density on NPY expression in cultured rat dorsal root ganglion neurones." Journal of the Autonomic Nervous System 81, no. 1-3 (2000): 128–38. http://dx.doi.org/10.1016/s0165-1838(00)00115-6.
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Schemann, M., and K. Tamura. "Presynaptic inhibitory effects of the peptides NPY, PYY and PP on nicotinic EPSPs in guinea-pig gastric myenteric neurones." Journal of Physiology 451, no. 1 (1992): 79–89. http://dx.doi.org/10.1113/jphysiol.1992.sp019154.
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CHEMINEAU, P., M. BLANC, A. CARATY, G. BRUNEAU, and P. MONGET. "Sous-nutrition, reproduction et système nerveux central chez les mammifères : rôle de la leptine." INRAE Productions Animales 12, no. 3 (1999): 217–23. http://dx.doi.org/10.20870/productions-animales.1999.12.3.3881.
Testo completoAbstract (sommario):
La relation entre la quantité de réserves adipeuses et la reproduction est connue depuis longtemps, mais le moyen par lequel les animaux sont capables d’estimer leur propre contenu en lipides corporels n’est connu que depuis peu. La leptine, une hormone principalement synthétisée et sécrétée par le tissu adipeux, identifiée en 1994, joue en grande partie ce rôle. Cette hormone agit sur des récepteurs spécifiques, présents dans de nombreux tissus. Chez les rongeurs, la leptine est impliquée dans la régulation centrale de l’ingestion alimentaire, de l’équilibre énergétique, de la thermorégulation, de l’activité reproductrice ainsi que dans la régulation de l’angiogenèse et des processus de cicatrisation.
 Pour la régulation de l’activité des neurones à LHRH (Luteinising Hormone-Releasing Hormone, le décapeptide hypothalamique qui contrôle la synthèse et la libération de LH et de FSH dans l’hypohyse), la leptine agit au niveau hypothalamique, sur la forme longue du récepteur. Son action, indirecte, passerait très probablement par des neuromédiateurs tels que le neuropeptide Y (NPY), la pro-opiomélanocortine (POMC), la sérotonine ou la galanine. Des récepteurs à la leptine se rencontrent également dans l’hypophyse, les gonades et le placenta. Chez les ruminants, la leptine et ses récepteurs n’ont été identifiés et clonés que récemment ; leurs rôles sont en cours de détermination.
22
Viñuela, Manuel Carrasco, and Philip Just Larsen. "Identification of NPY-induced c-Fos expression in hypothalamic neurones projecting to the dorsal vagal complex and the lower thoracic spinal cord." Journal of Comparative Neurology 438, no. 3 (2001): 286–99. http://dx.doi.org/10.1002/cne.1316.
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Krukoff, Teresa L. "Peptidergic inputs to sympathetic preganglionic neurons." Canadian Journal of Physiology and Pharmacology 65, no. 8 (1987): 1619–23. http://dx.doi.org/10.1139/y87-254.
Testo completoAbstract (sommario):
This paper presents data showing that the sympathetic autonomic areas of the cat thoracolumbar spinal cord contain nerve terminals and fibres with immunoreactivity for at least seven neuropeptides. The distribution in the intermediolateral cell column of the terminals and fibres which contain enkephalin-, neuropeptide Y-, neurotensin-, substance P-, and neurophysin II-like immunoreactivity (ENK, NPY, NT, SP, and NP2, respectively) suggests that these peptides are involved in more generalized functions of the autonomic nervous system. On the other hand, peaks in density of immunoreactivity at certain levels suggest that different levels of influence of sympathetic preganglionic neurons by the various peptides may occur along the length of the thoracolumbar cord. The distribution of terminals and fibres containing somatostatin- and oxytocin-like immunoreactivity (SS and OXY) suggests that these peptides may be part of specific pathways to particular sympathetic preganglionic neurons. The possible sources of the terminals and fibres containing ENK, NPY, NT, SS, and SP include the spinal cord and supraspinal areas, whereas the source of these structrues with OXY and NP2 is most likely supraspinal. The data suggest that coexistence of peptides and interactions between structures containing different neuropeptides occur in the spinal autonomic areas. It is speculated that neuropeptides have an important role to play in the regulation of the cardiovascular division of the autonomic nervous system.
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Hasseli, R., M. Tschernatsch, N. Heimann, et al. "POS0015 PREVALENCE OF NEUROPATHIES IN RHEUMATIC AND MUSCULOSKELETAL DISEASES." Annals of the Rheumatic Diseases 80, Suppl 1 (2021): 209.1–209. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3931.
Testo completoAbstract (sommario):
Background:In rheumatic and musculoskeletal diseases (RMDs), peripheral neurons can be affected, which can result in sensory symptoms like pain, burning, tingling, numbness and motor symptoms like muscle-atrophy or even paresis. More detailed knowledge about the prevalence and the cause of neuropathy (NP) in RMD are urgently needed, especially as RMD patients may develop different subtypes of NP.Objectives:The aim of this project was to assess the prevalence and the individual types of NP in rheumatoid arthritis (RA), spondyloarthritis (SpA) and systemic sclerosis (SSc) patients, and to elucidate the clinical, neurophysiological and neuropathologic features of associated NP.Methods:Baseline questionnaires and neurological and physical examination were used to elucidate the presence of neuropathic pain and autonomic dysfunction. Laboratory tests were performed to exclude other causes for NP. Electrophysiological tests were performed to differentiate demyelinating from axonal large fiber (LF)NPs. Additionally, skin biopsies were used to detect an involvement of small fibres (SF).Results:A total of 31 patients (median age 64 years (range 43-75)) were included. The majority of patients were female (90%). The mean disease duration was 10 years (1-41 years). More than 50% of the patients were diagnosed with RA, 7 with SpA and 6 with SSc. Of 31 patients, 48% (15/31) had clinical signs of NP and of those, neurophysiological examination showed 14 axonal 2, demyelinating and 4 mixed types. A combined LFNP and SFNP was present in 35% (11/31) of the patients. In 4 patients, only a SFNP was detectable, and in only two patients, no NP was detectable.Conclusion:NP was detectable in 94% (29/31) of the RMD patients, with LFNP predominating. This high proportion of NP in RMD suggests a surprisingly high coincidence of both diseases.Table 1.Subtypes of NP in RMDNumber of patientsAxonal NP14/31 (45%)Demyelinating NP2/31 (6%)Mixed axonal and demyelinating NP4/31 (12%)Sensory NP9/31 (26%)Sensorimotor NP5/31 (10%)Motor NP1/31 (3%)Disclosure of Interests:None declared.
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Murphy, Beth Ann, Xavier Fioramonti, Nina Jochnowitz, et al. "Fasting enhances the response of arcuate neuropeptide Y-glucose-inhibited neurons to decreased extracellular glucose." American Journal of Physiology-Cell Physiology 296, no. 4 (2009): C746—C756. http://dx.doi.org/10.1152/ajpcell.00641.2008.
Testo completoAbstract (sommario):
Fasting increases neuropeptide Y (NPY) expression, peptide levels, and the excitability of NPY-expressing neurons in the hypothalamic arcuate (ARC) nucleus. A subpopulation of ARC-NPY neurons (∼40%) are glucose-inhibited (GI)-type glucose-sensing neurons. Hence, they depolarize in response to decreased glucose. Because fasting enhances NPY neurotransmission, we propose that during fasting, GI neurons depolarize in response to smaller decreases in glucose. This increased excitation in response to glucose decreases would increase NPY-GI neuronal excitability and enhance NPY neurotransmission. Using an in vitro hypothalamic explant system, we show that fasting enhances NPY release in response to decreased glucose concentration. By measuring relative changes in membrane potential using a membrane potential-sensitive dye, we demonstrate that during fasting, a smaller decrease in glucose depolarizes NPY-GI neurons. Furthermore, incubation in low (0.7 mM) glucose enhanced while leptin (10 nM) blocked depolarization of GI neurons in response to decreased glucose. Fasting, leptin, and glucose-induced changes in NPY-GI neuron glucose sensing were mediated by 5′-AMP-activated protein kinase (AMPK). We conclude that during energy sufficiency, leptin reduces the ability of NPY-GI neurons to sense decreased glucose. However, after a fast, decreased leptin and glucose activate AMPK in NPY-GI neurons. As a result, NPY-GI neurons become depolarized in response to smaller glucose fluctuations. Increased excitation of NPY-GI neurons enhances NPY release. NPY, in turn, shifts energy homeostasis toward increased food intake and decreased energy expenditure to restore energy balance.
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Füzesi, Tamás, Gábor Wittmann, Zsolt Liposits, Ronald M. Lechan, and Csaba Fekete. "Contribution of Noradrenergic and Adrenergic Cell Groups of the Brainstem and Agouti-Related Protein-Synthesizing Neurons of the Arcuate Nucleus to Neuropeptide-Y Innervation of Corticotropin-Releasing Hormone Neurons in Hypothalamic Paraventricular Nucleus of the Rat." Endocrinology 148, no. 11 (2007): 5442–50. http://dx.doi.org/10.1210/en.2007-0732.
Testo completoAbstract (sommario):
CRH-synthesizing neurons in the hypothalamic paraventricular nucleus (PVN) integrate neuronal and hormonal inputs and serve as a final common pathway to regulate the hypothalamic-pituitary-adrenal axis. One of the neuronal regulators of CRH neurons is neuropeptide Y (NPY) contained in axons that densely innervate CRH neurons. The three main sources of NPY innervation of the PVN are the hypothalamic arcuate nucleus and the noradrenergic and adrenergic neurons of the brainstem. To elucidate the origin of the NPY-immunoreactive (NPY-IR) innervation to hypophysiotropic CRH neurons, quadruple-labeling immunocytochemistry for CRH, NPY, dopamine-β-hydroxylase, and phenylethanolamine-N-methyltransferase was performed. Approximately 63% of NPY-IR varicosities on the surface of CRH neurons were catecholaminergic (22% noradrenergic and 41% adrenergic), and 37% of NPY-IR boutons were noncatecholaminergic. By triple-labeling immunofluorescence detection of NPY, CRH, and agouti-related protein, a marker of NPY axons projecting from the arcuate nucleus, the noncatecholaminergic, NPY-ergic axon population was shown to arise primarily from the arcuate nucleus. When NPY was administered chronically into the cerebral ventricle of fed animals, a dramatic reduction of CRH mRNA was observed in the PVN (NPY vs. control integrated density units, 23.9 ± 2.7 vs. 77.09 ± 15.9). We conclude that approximately two thirds of NPY-IR innervation to hypophysiotropic CRH neurons originates from catecholaminergic neurons of the brainstem, whereas the remaining one third arises from the arcuate nucleus. The catecholaminergic NPY innervation seems to modulate the activation of CRH neurons in association with glucoprivation and infection, whereas the NPY input from the arcuate nucleus may contribute to inhibition of CRH neurons during fasting.
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Lee, Myung-Jun, Won-Tae Lee, and Chang-Jin Jeon. "Organization of Neuropeptide Y-Immunoreactive Cells in the Mongolian gerbil (Meriones unguiculatus) Visual Cortex." Cells 10, no. 2 (2021): 311. http://dx.doi.org/10.3390/cells10020311.
Testo completoAbstract (sommario):
Neuropeptide Y (NPY) is found throughout the central nervous system where it appears to be involved in the regulation of a wide range of physiological effects. The Mongolian gerbil, a member of the rodent family Muridae, is a diurnal animal and has been widely used in various aspects of biomedical research. This study was conducted to investigate the organization of NPY-immunoreactive (IR) neurons in the gerbil visual cortex using NPY immunocytochemistry. The highest density of NPY-IR neurons was located in layer V (50.58%). The major type of NPY-IR neuron was a multipolar round/oval cell type (44.57%). Double-color immunofluorescence revealed that 89.55% and 89.95% of NPY-IR neurons contained gamma-aminobutyric acid (GABA) or somatostatin, respectively. Several processes of the NPY-IR neurons surrounded GABAergic interneurons. Although 30.81% of the NPY-IR neurons contained calretinin, NPY and calbindin-D28K-IR neurons were co-expressed rarely (3.75%) and NPY did not co-express parvalbumin. Triple-color immunofluorescence with anti-GluR2 or CaMKII antibodies suggested that some non-GABAergic NPY-IR neurons may make excitatory synaptic contacts. This study indicates that NPY-IR neurons have a notable architecture and are unique subpopulations of the interneurons of the gerbil visual cortex, which could provide additional valuable data for elucidating the role of NPY in the visual process in diurnal animals.
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Hall, A. K., and S. E. MacPhedran. "Multiple mechanisms regulate sympathetic neuronal phenotype." Development 121, no. 8 (1995): 2361–71. http://dx.doi.org/10.1242/dev.121.8.2361.
Testo completoAbstract (sommario):
Adult rat sympathetic neurons can possess specific neuropeptides utilized as cotransmitters along with norepinephrine, but the factors that regulate their expression remain unknown. 60% of adult rat superior cervical ganglion (SCG) neurons express neuropeptide Y (NPY) in vivo. To determine whether the restricted expression was an intrinsic property of sympathetic ganglia, we examined if embryonic sympathetic precursors gave rise to NPY immunoreactive (-IR) neurons in vitro. After one week in culture, 60% of neurons derived from the E14.5 rat SCG were NPY-IR. Thus, ganglia isolated before peripheral target contact or preganglionic innervation were capable of regulating NPY expression both in the number of neurons with NPY and in the developmental timing of NPY expression. To determine if the restricted expression of NPY was a reflection of neuroblasts committed to an NPY fate, SCG precursors were labeled with a replication incompetent retrovirus carrying lacZ, and NPY expression in lacZ-labeled clones examined after one week. Two thirds of neuronal clones obtained were uniformly NPY-IR; that is, all neurons in a clone either possessed or lacked NPY. One-third of the neuronal clones were mixed and contained both neurons with and without NPY. We provide a novel demonstration that both lineage and environmental cues contribute to neuropeptide phenotype.
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Bugarith, Kishor, Thu T. Dinh, Ai-Jun Li, Robert C. Speth, and Sue Ritter. "Basomedial Hypothalamic Injections of Neuropeptide Y Conjugated to Saporin Selectively Disrupt Hypothalamic Controls of Food Intake." Endocrinology 146, no. 3 (2005): 1179–91. http://dx.doi.org/10.1210/en.2004-1166.
Testo completoAbstract (sommario):
Neuropeptide Y (NPY) conjugated to saporin (NPY-SAP), a ribosomal inactivating toxin, is a newly developed compound designed to selectively target and lesion NPY receptor-expressing cells. We injected NPY-SAP into the basomedial hypothalamus (BMH), just dorsal to the arcuate nucleus (ARC), to investigate its neurotoxicity and to determine whether ARC NPY neurons are required for glucoprivic feeding. We found that NPY-SAP profoundly reduced NPY Y1 receptor and αMSH immunoreactivity, as well as NPY, Agouti gene-related protein (AGRP), and cocaine and amphetamine-related transcript mRNA expression in the BMH. NPY-SAP lesions were localized to the injection site with no evidence of retrograde transport by hindbrain NPY neurons with BMH terminals. These lesions impaired responses to intracerebroventricular (icv) leptin (5 μg/5 μl·d) and ghrelin (2 μg/5 μl), which are thought to alter feeding primarily by actions on ARC NPY/AGRP and proopiomelanocortin/cocaine and amphetamine-related transcript neurons. However, the hypothesis that NPY/AGRP neurons are required downstream mediators of glucoprivic feeding was not supported. Although NPY/AGRP neurons were destroyed by NPY-SAP, the lesion did not impair either the feeding or the hyperglycemic response to 2-deoxy-d-glucose-induced blockade of glycolysis use. Similarly, responses to glucagon-like peptide-1 (GLP-1, 5 μg/3 μl icv), NPY (5 μg/3 μl icv), cholecystokinin octapeptide (4 μg/kg ip), and β-mercaptoacetate (68 mg/kg ip) were not altered by the NPY-SAP lesion. Thus, NPY-SAP destroyed NPY receptor-expressing neurons in the ARC and selectively disrupted controls of feeding dependent on those neurons but did not disrupt peptidergic or metabolic controls dependent upon circuitry outside the BMH.
30
Kim, Ginah L., Sandeep S. Dhillon, and Denise D. Belsham. "Kisspeptin Directly Regulates Neuropeptide Y Synthesis and Secretion via the ERK1/2 and p38 Mitogen-Activated Protein Kinase Signaling Pathways in NPY-Secreting Hypothalamic Neurons." Endocrinology 151, no. 10 (2010): 5038–47. http://dx.doi.org/10.1210/en.2010-0521.
Testo completoAbstract (sommario):
Kisspeptin is a key component of reproduction that directly stimulates GnRH neurons. However, recent studies indicate that kisspeptin can indirectly stimulate GnRH neurons through unidentified afferent networks. Neuropeptide Y (NPY) is another key reproductive hormone that is an afferent stimulator of GnRH neurons. Herein, we report kisspeptin receptor Kiss1r mRNA expression in native NPY neurons FAC-sorted from NPY-GFP transgenic mice. Thus, we hypothesized that kisspeptin indirectly stimulates GnRH neurons through direct regulation of NPY neurons. Using hypothalamic NPY-secreting cell lines, we determined that kisspeptin stimulates NPY mRNA expression and secretion in the mHypoE-38 cells, but not the mHypoE-42 cells, using quantitative RT-PCR and enzyme immunoassays. Furthermore, agouti-related peptide, ghrelin, neurotensin, or Kiss1r mRNA expression was not changed upon exposure to kisspeptin in either cell line. These results concur with our previous work identifying the mHypoE-38 cell line as a putative reproductive NPY neuron and the mHypoE-42 cell line as a potential feeding-related NPY neuron. In the mHypoE-38 cells, kisspeptin activated the ERK1/2 and p38 MAPK kinases as shown by Western blot analysis. Moreover, inhibiting the ERK1/2 and p38 pathways with U0126 and SB239063, respectively, prevented kisspeptin induction of NPY mRNA expression and secretion. Altogether, we find that kisspeptin directly regulates NPY synthesis and secretion via the ERK1/2 and p38 MAPK pathways in a NPY-secreting cell line, and we propose NPY neurons as an afferent network by which kisspeptin indirectly stimulates GnRH secretion.
31
Wiley, J. W., R. A. Gross, and R. L. MacDonald. "Agonists for neuropeptide Y receptor subtypes NPY-1 and NPY-2 have opposite actions on rat nodose neuron calcium currents." Journal of Neurophysiology 70, no. 1 (1993): 324–30. http://dx.doi.org/10.1152/jn.1993.70.1.324.
Testo completoAbstract (sommario):
1. The whole-cell variation of the patch-clamp technique was used to study the effect of neuropeptide Y (NPY) and preferential agonists for the NPY-1 and NPY-2 receptor subtypes on voltage-dependent calcium currents in acutely dissociated postnatal rat nodose ganglion neurons. 2. Both low- and high-threshold calcium current components were present. NPY altered voltage-dependent calcium currents in approximately 50% of neurons studied. NPY (0.1-100 nM, ED50 6 nM) decreased the peak amplitude of transient high-threshold calcium currents in approximately 45% of the neurons. NPY (100 nM) decreased the peak amplitude of these currents 31 +/- 5% (mean +/- SE). However, in approximately 5% of the neurons NPY (100 nM) caused a reversible and reproducible increase in transient high-threshold calcium currents of 21 +/- 4%. NPY did not affect either transient low-threshold or slowly inactivating high-threshold calcium current components. 3. Application of the C-terminal fragment NPY 13-36 (100 nM), a preferential agonist for NPY-2 receptors, reversibly decreased the peak amplitude of transient high-threshold calcium currents by 26 +/- 5% in 9 of 20 cells (45%). Application of [Pro34]-NPY (100 nM), a preferential agonist for NPY-1 receptors, reversibly increased the peak amplitude of transient high-threshold calcium currents 20 +/- 4% in 23 out of 48 neurons (48%). Six of 20 neurons (30%) responded to application of both agonists. Neither the NPY-1 nor NPY-2 agonists affected transient low-threshold or slowly inactivating high-threshold calcium current components.(ABSTRACT TRUNCATED AT 250 WORDS)
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Sarkar, Sumit, та Ronald M. Lechan. "Central Administration of Neuropeptide Y Reduces α-Melanocyte-Stimulating Hormone-Induced Cyclic Adenosine 5′-Monophosphate Response Element Binding Protein (CREB) Phosphorylation in Pro-Thyrotropin-Releasing Hormone Neurons and Increases CREB Phosphorylation in Corticotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus". Endocrinology 144, № 1 (2003): 281–91. http://dx.doi.org/10.1210/en.2002-220675.
Testo completoAbstract (sommario):
Abstract Neuropeptide Y (NPY) has a potent inhibitory effect on TRH gene expression in the paraventricular nucleus (PVN) and contributes to the fall in circulating thyroid hormone levels during fasting mediated by a reduction in serum leptin levels. Because α-MSH activates the TRH gene by increasing the phosphorylation of CREB in the nucleus of these neurons, we raised the possibility that at least one of the mechanisms by which NPY reduces TRH mRNA in hypophysiotropic neurons is by antagonizing the ability of α-MSH to phosphorylate CREB. As NPY increases CRH mRNA in the hypothalamus, we further determined whether intracerebroventricular (icv) administration of NPY regulates the phosphorylation of CREB in hypophysiotropic CRH neurons. NPY [10 μg in artificial CSF (aCSF)] was administered into the lateral ventricle icv 30 min before the icv administration of aCSF or α-MSH (10 μg in aCSF), the latter in a dose previously demonstrated to increase proTRH mRNA and phosphorylate CREB in TRH neurons. By double-labeling immunocytochemistry, only few TRH neurons in the PVN contained phosphoCREB (PCREB) in animals treated only with aCSF (4 ± 0.2%) or with NPY followed by aCSF (9.7 ± 2.5), whereas α-MSH-infused animals dramatically increased the percentage of TRH neurons containing PCREB (75.3 ± 6.9%). Pretreatment with NPY before α-MSH infusion, however, significantly reduced the percentage of TRH neurons containing PCREB (40.8 ± 3.5%) compared with α-MSH infused animals (P = 0.01). Only 12.2 ± 0.9% of CRH neurons of the medial parvocellular neurons contained PCREB nuclei in vehicle-treated animals, whereas 30 min following NPY infusion, the number of CRH neurons containing PCREB increased dramatically to 88 ± 2.9%. Whereas α-MSH infusion increased the percentage of CRH neurons that contained PCREB to 56 ± 2.2% compared with control, animals pretreated with NPY further increased the number of CRH neurons colocalizing with PCREB to 87 ± 2.5%. These data demonstrate a functional interaction between NPY and α-MSH in the regulation of proTRH neurons in the PVN, suggesting that NPY can antagonize α-MSH induced activation of the TRH gene by interfering with melanocortin signaling at the postreceptor level, preventing the phosphorylation of CREB. In contrast, NPY infusion increases the phosphorylation of CREB in CRH neurons, indicating that NPY has independent effects on discrete populations of neurons in the PVN, presumably mediated through different signaling mechanisms.
33
Feng, Bing, Frank Greenway, Jerney Harms, et al. "OR23-3 Hunger Hormone Asprosin Activates Orexigenic Neurons via SK Currents." Journal of the Endocrine Society 6, Supplement_1 (2022): A19. http://dx.doi.org/10.1210/jendso/bvac150.039.
Testo completoAbstract (sommario):
Abstract Neurons that co-express the orexigenic agouti-related protein (AgRP) and neuropeptide Y (NPY) are indispensable for normal feeding behavior. Firing activities of AgRP/NPY neurons dynamically fluctuate with energy status and coordinate appropriate feeding behavior to meet nutritional demands. We previously demonstrated that asprosin, a recently discovered fasting-induced glucogenic and orexigenic hormone, crosses the blood-brain barrier and directly activates the orexigenic AgRP/NPY neurons via a cyclic cAMP-dependent pathway. However, intrinsic mechanisms on how asprosin regulates AgRP/NPY neural activities during the fed-to-fasted transition are not fully understood. In the satiated mice with low circulating levels of asprosin, we found that AgRP/NPY neurons expressed high levels of the small conductance calcium-activated potassium channel 3 (SK3) and were inhibited by SK3-mediated potassium currents. Conversely, in 24 hour-fasting mice with high levels of asprosin, AgRP/NPY neurons expressed low levels of SK3 and were activated via inhibition of SK3-mediated potassium currents. Notably, the stimulatory effects of asprosin on AgRP/NPY neurons were blunted in mice with SK3 selectively deleted in the AgRP/NPY neurons, further supporting a mediating role of SK3. Moreover, we also identified protein tyrosine phosphatase receptor δ (Ptprd), a membrane-bound phosphatase receptor, as the orexigenic asprosin-receptor. Deletion of Ptprd in AgRP/NPY neurons abolished asprosin's stimulatory effect on SK3-mediated currents and protected mice from diet-induced obesity. Lastly, increased circulating levels of asprosin promoted hyperphagia, body weight gain, and glucose intolerance. On the other hand, anti-asprosin antibody treatment decreased food intake and body weight by inhibiting AgRP/NPY and other orexigenic hypothalamic neurons via SK currents stimulation. In summary, our data support a model that asprosin acts on Ptprd expressed by AgRP/NPY neurons to inhibit SK3 current, further activating AgRP/NPY neurons to increase food intake and body weight. Our findings also provided preclinical evidence that asprosin-neutralizing antibodies could be used to treat obesity. Presentation: Monday, June 13, 2022 11:45 a.m. - 12:00 p.m.
34
Marston, Oliver J., Paul Hurst, Mark L. Evans, Denis I. Burdakov, and Lora K. Heisler. "Neuropeptide Y Cells Represent a Distinct Glucose-Sensing Population in the Lateral Hypothalamus." Endocrinology 152, no. 11 (2011): 4046–52. http://dx.doi.org/10.1210/en.2011-1307.
Testo completoAbstract (sommario):
The maintenance of appropriate glucose levels is necessary for survival. Within the brain, specialized neurons detect glucose fluctuations and alter their electrical activity. These glucose-sensing cells include hypothalamic arcuate nucleus neurons expressing neuropeptide Y (NPY) and lateral hypothalamic area (LHA) neurons expressing orexin/hypocretins (ORX) or melanin-concentrating hormone (MCH). Within the LHA, a population of NPY-expressing cells exists; however, their ability to monitor energy status is unknown. We investigated whether NPY neurons located in the LHA, a classic hunger center, detect and respond to fluctuations in glucose availability and compared these responses with those of known LHA glucose sensors expressing ORX or MCH. Using mice expressing green fluorescent protein under the control of NPY regulatory elements, we identified LHA NPY cells and explored their anatomical distribution, neurochemical and electrical properties, in vivo responses to fasting and insulin-induced hypoglycemia, and in situ electrical responses to extracellular glucose. We report that NPY, ORX, and MCH are expressed in nonoverlapping populations within the LHA. Subpopulations of LHA NPY neurons were activated in vivo by both a 6-h fast and insulin-induced hypoglycemia. Likewise, increased extracellular glucose suppressed the electrical activity of approximately 70% of LHA NPY neurons in situ, eliciting hyperpolarization and activating background K+ currents. Furthermore, we report that the glucose sensitivity of LHA NPY neurons is significantly different from neighboring ORX and MCH neurons. These data suggest that NPY-expressing cells in the LHA are a novel population of glucose-sensing neurons that represent a new player in the brain circuitry integrating information about glucose homeostasis.
35
Wahle, P., T. Gorba, M. J. Wirth, and K. Obst-Pernberg. "Specification of neuropeptide Y phenotype in visual cortical neurons by leukemia inhibitory factor." Development 127, no. 9 (2000): 1943–51. http://dx.doi.org/10.1242/dev.127.9.1943.
Testo completoAbstract (sommario):
Building the complex mammalian neocortex requires appropriate numbers of neurochemically specified neurons. It is not clear how the highly diverse cortical interneurons acquire their distinctive phenotypes. The lack of genetic determination implicates environmental factors in this selection and specification process. We analysed, in organotypic visual cortex cultures, the specification of neurons expressing neuropeptide Y (NPY), a potent anticonvulsant. Endogenous brain-derived neurotrophic factor and neurotrophin 4/5 play no role in early NPY phenotype specification. Rather, the decision to express NPY is made during a period of molecular plasticity during which differentiating neurons with the potential to express NPY compete for the cytokine leukemia inhibitory factor which is produced in the cortex, but is negatively regulated by thalamic afferences. The neurons that fail in this competition are parvalbuminergic basket and chandelier neurons, which express NPY transiently, but will not acquire a permanent NPY expression. They switch into a facultative NPY expression mode, and remain responsive to the neurotrophins which modulate NPY expression later in development.
36
Dhillon, Sandeep S., Sean A. McFadden, Jennifer A. Chalmers, Maria-Luisa Centeno, Ginah L. Kim, and Denise D. Belsham. "Cellular Leptin Resistance Impairs the Leptin-Mediated Suppression of Neuropeptide Y Secretion in Hypothalamic Neurons." Endocrinology 152, no. 11 (2011): 4138–47. http://dx.doi.org/10.1210/en.2011-0178.
Testo completoAbstract (sommario):
Evidence shows that neuropeptide Y (NPY) neurons are involved in mediating the anorexigenic action of leptin via neuronal circuits in the hypothalamus. However, studies have produced limited data on the cellular processes involved and whether hypothalamic NPY neurons are susceptible to cellular leptin resistance. To investigate the direct regulation of NPY secretion by leptin, we used novel NPY-synthesizing, immortalized mHypoA-NPY/green fluorescent protein and mHypoA-59 hypothalamic cell lines derived from adult hypothalamic primary cultures. We report that leptin treatment significantly suppressed NPY secretion in the cells by approximately 20%. We found a decrease in c-fos expression upon leptin exposure, indicating deactivation or hyperpolarization of the neurons. Protein analysis indicated that leptin inhibits AMP-activated protein kinase (AMPK) activity and activates acetyl-coenzyme A carboxylase in NPY neurons, supporting the hypothesis of an AMPK-dependent mechanism. Inhibiting both AMPK with Compound C or phosphatidylinositol 3 kinase (PI3K) with 2-(4-morpholinyl)-8-phenyl-1(4H)-1-benzopyran-4-one hydrochloride prevented the leptin-mediated decrease in NPY secretion, indicating both AMPK- and PI3K-mediated mechanisms. Further, NPY secretion was stimulated by 30% by the AMPK activator, aminoimidazole carboxamide ribonucleotide. Importantly, prolonged leptin exposure in the mHypoA-NPY/green fluorescent protein cells prevented leptin-induced changes in AMPK phosphorylation and suppression of NPY secretion, indicating that NPY neurons are susceptible to leptin resistance. Our studies indicate that AMPK and PI3K pathways are involved in leptin action in NPY neurons and that leptin resistance blocks the feedback response likely required to maintain energy homeostasis.
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West, Katherine Stuhrman, and Aaron G. Roseberry. "Neuropeptide-Y alters VTA dopamine neuron activity through both pre- and postsynaptic mechanisms." Journal of Neurophysiology 118, no. 1 (2017): 625–33. http://dx.doi.org/10.1152/jn.00879.2016.
Testo completoAbstract (sommario):
The mesocorticolimbic dopamine system, the brain’s reward system, regulates many different behaviors including food intake, food reward, and feeding-related behaviors, and there is increasing evidence that hypothalamic feeding-related neuropeptides alter dopamine neuron activity to affect feeding. For example, neuropeptide-Y (NPY), a strong orexigenic hypothalamic neuropeptide, increases motivation for food when injected into the ventral tegmental area (VTA). How NPY affects the activity of VTA dopamine neurons to regulate feeding behavior is unknown, however. In these studies we have used whole cell patch-clamp electrophysiology in acute brain slices from mice to examine how NPY affects VTA dopamine neuron activity. NPY activated an outward current that exhibited characteristics of a G protein-coupled inwardly rectifying potassium channel current in ~60% of dopamine neurons tested. In addition to its direct effects on VTA dopamine neurons, NPY also decreased the amplitude and increased paired-pulse ratios of evoked excitatory postsynaptic currents in a subset of dopamine neurons, suggesting that NPY decreases glutamatergic transmission through a presynaptic mechanism. Interestingly, NPY also strongly inhibited evoked inhibitory postsynaptic currents onto dopamine neurons by a presynaptic mechanism. Overall these studies demonstrate that NPY utilizes multiple mechanisms to affect VTA dopamine neuron activity, and they provide an important advancement in our understanding of how NPY acts in the VTA to control feeding behavior. NEW & NOTEWORTHY Neuropeptide-Y (NPY) has been shown to act on mesolimbic dopamine circuits to increase motivated behaviors toward food, but it is unclear exactly how NPY causes these responses. Here, we demonstrate that NPY directly inhibited a subset of ventral tegmental area (VTA) dopamine neurons through the activation of G protein-coupled inwardly rectifying potassium currents, and it inhibited both excitatory postsynaptic currents and inhibitory postsynaptic currents onto subsets of dopamine neurons through a presynaptic mechanism. Thus NPY uses multiple mechanisms to dynamically control VTA dopamine neuron activity.
38
Xu, Jing, Melissa A. Kirigiti, Michael A. Cowley, Kevin L. Grove, and M. Susan Smith. "Suppression of Basal Spontaneous Gonadotropin-Releasing Hormone Neuronal Activity during Lactation: Role of Inhibitory Effects of Neuropeptide Y." Endocrinology 150, no. 1 (2008): 333–40. http://dx.doi.org/10.1210/en.2008-0962.
Testo completoAbstract (sommario):
Increased neuropeptide Y (NPY) activity drives the chronic hyperphagia of lactation and may contribute to the suppression of GnRH activity. The majority of GnRH neurons are contacted by NPY fibers, and GnRH cells express NPY Y5 receptor (Y5R). Therefore, NPY provides a neurocircuitry for information about food intake/energy balance to be directly transmitted to GnRH neurons. To investigate the effects of lactation on GnRH neuronal activity, hypothalamic slices were prepared from green fluorescent protein-GnRH transgenic rats. Extracellular loose-patch recordings determined basal GnRH neuronal activity from slices of ovariectomized control and lactating rats. Compared with controls, hypothalamic slices from lactating rats had double the number of quiescent GnRH neurons (14.51 ± 2.86 vs. 7.04 ± 2.84%) and significantly lower firing rates of active GnRH neurons (0.25 ± 0.02 vs. 0.37 ± 0.03 Hz). To study the NPY-postsynaptic Y5R system, whole-cell current-clamp recordings were performed in hypothalamic slices from control rats to examine NPY/Y5R antagonist effects on GnRH neuronal resting membrane potential. Under tetrodotoxin treatment, NPY hyperpolarized GnRH neurons from −56.7 ± 1.94 to −62.1 ± 1.83 mV; NPY’s effects were blocked by Y5R antagonist. To determine whether increased endogenous NPY tone contributes to GnRH neuronal suppression during lactation, hypothalamic slices were treated with Y5R antagonist. A significantly greater percentage of GnRH cells were activated in slices from lactating rats (52%) compared with controls (28%). These results suggest that: 1) basal GnRH neuronal activity is suppressed during lactation; 2) NPY can hyperpolarize GnRH neurons via postsynaptic Y5R; and 3) increased inhibitory NPY tone during lactation is a component of the mechanisms responsible for suppression of GnRH neuronal activity. Neuropeptide Y (NPY) directly hyperpolarizes GnRH neurons via postsynaptic NPY Y5 receptor. Increased inhibitory NPY tone during lactation is an important component of the suppression of GnRH neuronal activity.
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Sun, Lihjen, and Richard J. Miller. "Multiple Neuropeptide Y Receptors Regulate K+ and Ca2+ Channels in Acutely Isolated Neurons From the Rat Arcuate Nucleus." Journal of Neurophysiology 81, no. 3 (1999): 1391–403. http://dx.doi.org/10.1152/jn.1999.81.3.1391.
Testo completoAbstract (sommario):
Multiple neuropeptide Y receptors regulate potassium and calcium channels in acutely isolated neurons from the arcuate nucleus of the rat. We examined the effects of neuropeptide Y (NPY) and related peptides on Ca2+ and K+ currents in acutely isolated neurons from the arcuate nucleus of the rat. NPY analogues that activated all of the known NPY receptors (Y1–Y5), produced voltage-dependent inhibition of Ca2+ currents and activation of inwardly rectifying K+ currents in arcuate neurons. Both of these effects could occur simultaneously in the same cells. In some cells, activation of Y4 NPY receptors also caused oscillations in [Ca2+]i. NPY hyperpolarized arcuate neurons through the activation of a K+ conductance and increased the spike threshold. Molecular biological studies indicated that arcuate neurons possessed all of the previously cloned NPY receptor types (Y1, Y2, Y4, and Y5). Thus activation of multiple types NPY receptors on arcuate neurons can regulate both Ca2+ and K+ conductances leading to a reduction in neuronal excitability and a suppression of neurotransmitter release.
40
Mano-Otagiri, Asuka, Takahiro Nemoto, Azusa Sekino, et al. "Growth Hormone-Releasing Hormone (GHRH) Neurons in the Arcuate Nucleus (Arc) of the Hypothalamus Are Decreased in Transgenic Rats Whose Expression of Ghrelin Receptor Is Attenuated: Evidence that Ghrelin Receptor Is Involved in the Up-Regulation of GHRH Expression in the Arc." Endocrinology 147, no. 9 (2006): 4093–103. http://dx.doi.org/10.1210/en.2005-1619.
Testo completoAbstract (sommario):
GH secretagogue (GHS)/ghrelin stimulates GH secretion by binding mainly to its receptor (GHS-R) on GHRH neurons in the arcuate nucleus (Arc) of the hypothalamus. GHRH, somatostatin, and neuropeptide Y (NPY) in the hypothalamus are involved in the regulatory mechanism of GH secretion. We previously created transgenic (Tg) rats whose GHS-R expression is reduced in the Arc, showing lower body weight and shorter nose-tail length. GH secretion is decreased in female Tg rats. To clarify how GHS-R affects GHRH expression in the Arc, we compared the numbers of GHS-R-positive, GHRH, and NPY neurons between Tg and wild-type rats. Immunohistochemical analysis showed that the numbers of GHS-R-positive neurons, GHRH neurons, and GHS-R-positive GHRH neurons were reduced in Tg rats, whereas the numbers of NPY neurons and GHS-R-positive NPY neurons did not differ between the two groups. The numbers of Fos-positive neurons and Fos-positive GHRH neurons in response to KP-102 were decreased in Tg rats. Competitive RT-PCR analysis of GHRH mRNA expression in the cultured hypothalamic neurons showed that KP-102 increased NPY mRNA expression level and that NPY decreased GHRH mRNA expression level. KP-102 increased GHRH mRNA expression level in the presence of anti-NPY IgG. GH increased somatostatin mRNA expression. Furthermore, GH and somatostatin decreased GHRH mRNA expression, whereas KP-102 showed no significant effect on somatostatin mRNA expression. These results suggest that GHS-R is involved in the up-regulation of GHRH and NPY expression and that NPY, somatostatin, and GH suppress GHRH expression. It is also suggested that the reduction of GHRH neurons of Tg rats is induced by a decrease in GHS-R expression.
41
Partridge, John G., Megan J. Janssen, David Y. T. Chou, Ken Abe, Zofia Zukowska, and Stefano Vicini. "Excitatory and Inhibitory Synapses in Neuropeptide Y–Expressing Striatal Interneurons." Journal of Neurophysiology 102, no. 5 (2009): 3038–45. http://dx.doi.org/10.1152/jn.00272.2009.
Testo completoAbstract (sommario):
Although rare, interneurons are pivotal in governing striatal output by extensive axonal arborizations synapsing on medium spiny neurons. Using a genetically modified mouse strain in which a green fluorescent protein (GFP) is driven to be expressed under control of the neuropeptide Y (NPY) promoter, we identified NPY interneurons and compared them with striatal principal neurons. We found that the bacteria artificial chromosome (BAC)- npy mouse expresses GFP with high fidelity in the striatum to the endogenous expression of NPY. Patch-clamp analysis from NPY neurons showed a heterogeneous population of striatal interneurons. In the majority of cells, we observed spontaneous firing of action potentials in extracellular recordings. On membrane rupture, most NPY interneurons could be classified as low-threshold spiking interneurons and had high-input resistance. Voltage-clamp recordings showed that both GABA and glutamate gated ion channels mediate synaptic inputs onto these striatal interneurons. AMPA receptor–mediated spontaneous excitatory postsynaptic currents (sEPSCs) were small in amplitude and infrequent in NPY neurons. Evoked EPSCs did not show short-term plasticity but some rectification. Evoked N-methyl-d-aspartate (NMDA) EPSCs had fast decay kinetics and were poorly sensitive to an NR2B subunit containing NMDA receptor blocker. Spontaneous inhibitory postsynaptic currents (sIPSCs) were mediated by GABAA receptors and were quite similar among all striatal neurons studied. On the contrary, evoked IPSCs decayed faster in NPY neurons than in other striatal neurons. These data report for the first time specific properties of synaptic transmission to NPY striatal interneurons.
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Turi, Gergely F., Zsolt Liposits, Suzanne M. Moenter, Csaba Fekete, and Erik Hrabovszky. "Origin of Neuropeptide Y-Containing Afferents to Gonadotropin-Releasing Hormone Neurons in Male Mice." Endocrinology 144, no. 11 (2003): 4967–74. http://dx.doi.org/10.1210/en.2003-0470.
Testo completoAbstract (sommario):
Abstract The origin of neuropeptide Y (NPY) afferents to GnRH neurons was investigated in male mice. Neonatal lesioning of the hypothalamic arcuate nuclei (ARC) with monosodium glutamate markedly reduced the number of NPY fibers in the preoptic area as well as the frequency of their contacts with perikarya and proximal dendrites of GnRH neurons. Dual-label immunofluorescence studies to determine the precise contribution of the ARC to the innervation of GnRH neurons by NPY axons were carried out on transgenic mice in which enhanced green fluorescent protein was expressed under the control of the GnRH promoter (GnRH-enhanced green fluorescent protein mice). The combined application of red Cy3 and blue AMCA fluorochromogenes established that 49.1 ± 7.3% of NPY axons apposed to green GnRH neurons also contained agouti-related protein (AGRP), a selective marker for NPY axons arising from the ARC. Immunoelectronmicroscopic analysis detected symmetric synapses between AGRP fibers and GnRH-immunoreactive perikarya. Additional triple-fluorescence experiments revealed the presence of dopamine-β-hydroxylase immunoreactivity within 25.4 ± 3.3% of NPY afferents to GnRH neurons. This enzyme marker enabled the selective labeling of NPY pathways ascending from noradrenergic/adrenergic cell populations of the brain stem, thus defining a second important source for NPY-containing fibers regulating GnRH cells. The absence of both topographic markers (AGRP and dopamine-β-hydroxylase) within 26% of NPY contacts suggests that additional sources of NPY fibers to GnRH neurons exist. Future studies will address distinct functions of the two identified NPY systems in the afferent neuronal regulation of the GnRH system.
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Aveleira, Célia A., Mariana Botelho, Sara Carmo-Silva, et al. "Neuropeptide Y stimulates autophagy in hypothalamic neurons." Proceedings of the National Academy of Sciences 112, no. 13 (2015): E1642—E1651. http://dx.doi.org/10.1073/pnas.1416609112.
Testo completoAbstract (sommario):
Aging is characterized by autophagy impairment that contributes to age-related disease aggravation. Moreover, it was described that the hypothalamus is a critical brain area for whole-body aging development and has impact on lifespan. Neuropeptide Y (NPY) is one of the major neuropeptides present in the hypothalamus, and it has been shown that, in aged animals, the hypothalamic NPY levels decrease. Because caloric restriction (CR) delays aging, at least in part, by stimulating autophagy, and also increases hypothalamic NPY levels, we hypothesized that NPY could have a relevant role on autophagy modulation in the hypothalamus. Therefore, the aim of this study was to investigate the role of NPY on autophagy in the hypothalamus. Using both hypothalamic neuronal in vitro models and mice overexpressing NPY in the hypothalamus, we observed that NPY stimulates autophagy in the hypothalamus. Mechanistically, in rodent hypothalamic neurons, NPY increases autophagy through the activation of NPY Y1 and Y5 receptors, and this effect is tightly associated with the concerted activation of PI3K, MEK/ERK, and PKA signaling pathways. Modulation of hypothalamic NPY levels may be considered a potential strategy to produce protective effects against hypothalamic impairments associated with age and to delay aging.
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Tanaka, Masaki, Shunji Yamada, and Yoshihisa Watanabe. "The Role of Neuropeptide Y in the Nucleus Accumbens." International Journal of Molecular Sciences 22, no. 14 (2021): 7287. http://dx.doi.org/10.3390/ijms22147287.
Testo completoAbstract (sommario):
Neuropeptide Y (NPY), an abundant peptide in the central nervous system, is expressed in neurons of various regions throughout the brain. The physiological and behavioral effects of NPY are mainly mediated through Y1, Y2, and Y5 receptor subtypes, which are expressed in regions regulating food intake, fear and anxiety, learning and memory, depression, and posttraumatic stress. In particular, the nucleus accumbens (NAc) has one of the highest NPY concentrations in the brain. In this review, we summarize the role of NPY in the NAc. NPY is expressed principally in medium-sized aspiny neurons, and numerous NPY immunoreactive fibers are observed in the NAc. Alterations in NPY expression under certain conditions through intra-NAc injections of NPY or receptor agonists/antagonists revealed NPY to be involved in the characteristic functions of the NAc, such as alcohol intake and drug addiction. In addition, control of mesolimbic dopaminergic release via NPY receptors may take part in these functions. NPY in the NAc also participates in fat intake and emotional behavior. Accumbal NPY neurons and fibers may exert physiological and pathophysiological actions partly through neuroendocrine mechanisms and the autonomic nervous system.
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Klenke, Ulrike, Stephanie Constantin, and Susan Wray. "Neuropeptide Y Directly Inhibits Neuronal Activity in a Subpopulation of Gonadotropin-Releasing Hormone-1 Neurons via Y1 Receptors." Endocrinology 151, no. 6 (2010): 2736–46. http://dx.doi.org/10.1210/en.2009-1198.
Testo completoAbstract (sommario):
Neuropeptide Y (NPY), a member of the pancreatic polypeptide family, is an orexigenic hormone. GnRH-1 neurons express NPY receptors. This suggests a direct link between metabolic function and reproduction. However, the effect of NPY on GnRH-1 cells has been variable, dependent on metabolic and reproductive status of the animal. This study circumvents these issues by examining the role of NPY on GnRH-1 neuronal activity in an explant model that is based on the extra-central nervous system origin of GnRH-1 neurons. These prenatal GnRH-1 neurons express many receptors found in GnRH-1 neurons in the brain and use similar transduction pathways. In addition, these GnRH-1 cells exhibit spontaneous and ligand-induced oscillations in intracellular calcium as well as pulsatile calcium-controlled GnRH-1 release. Single-cell PCR determined that prenatal GnRH-1 neurons express the G protein-coupled Y1 receptor (Y1R). To address the influence of NPY on GnRH-1 neuronal activity, calcium imaging was used to monitor individual and population dynamics. NPY treatment, mimicked with Y1R agonist, significantly decreased the number of calcium peaks per minute in GnRH-1 neurons and was prevented by a Y1R antagonist. Pertussis toxin blocked the effect of NPY on GnRH-1 neuronal activity, indicating the coupling of Y1R to inhibitory G protein. The NPY-induced inhibition was independent of the adenylate cyclase pathway but mediated by the activation of G protein-coupled inwardly rectifying potassium channels. These results indicate that at an early developmental stage, GnRH-1 neuronal activity can be directly inhibited by NPY via its Y1R.
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Damon, Deborah H. "TH and NPY in sympathetic neurovascular cultures: role of LIF and NT-3." American Journal of Physiology-Cell Physiology 294, no. 1 (2008): C306—C312. http://dx.doi.org/10.1152/ajpcell.00214.2007.
Testo completoAbstract (sommario):
The sympathetic nervous system is an important determinant of vascular function. The effects of the sympathetic nervous system are mediated via release of neurotransmitters and neuropeptides from postganglionic sympathetic neurons. The present study tests the hypothesis that vascular smooth muscle cells (VSM) maintain adrenergic neurotransmitter/neuropeptide expression in the postganglionic sympathetic neurons that innervate them. The effects of rat aortic and tail artery VSM (AVSM and TAVSM, respectively) on neuropeptide Y (NPY) and tyrosine hydroxylase (TH) were assessed in cultures of dissociated sympathetic neurons. AVSM decreased TH (39 ± 12% of control) but did not affect NPY. TAVSM decreased TH (76 ± 10% of control) but increased NPY (153 ± 20% of control). VSM expressed leukemia inhibitory factor (LIF) and neurotrophin-3 (NT-3), which are known to modulate NPY and TH expression. Sympathetic neurons innervating blood vessels expressed LIF and NT-3 receptors. Inhibition of LIF inhibited the effect of AVSM on TH. Inhibition of neurotrophin-3 (NT-3) decreased TH and NPY in neurons grown in the presence of TAVSM. These data suggest that vascular-derived LIF decreases TH and vascular-derived NT-3 increases or maintains NPY and TH expression in postganglionic sympathetic neurons. NPY and TH in vascular sympathetic nerves are likely to modulate NPY and/or norepinephrine release from these nerves and are thus likely to affect blood flow and blood pressure. The present studies suggest a novel mechanism whereby VSM would modulate sympathetic control of vascular function.
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Oh, Youjin, Eun-Seon Yoo, Sang Hyeon Ju, et al. "GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice." PLOS Biology 21, no. 8 (2023): e3002252. http://dx.doi.org/10.1371/journal.pbio.3002252.
Testo completoAbstract (sommario):
It is well known that the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons increase appetite and decrease thermogenesis. Previous studies demonstrated that optogenetic and/or chemogenetic manipulations of NPY/AgRP neuronal activity alter food intake and/or energy expenditure (EE). However, little is known about intrinsic molecules regulating NPY/AgRP neuronal excitability to affect long-term metabolic function. Here, we found that the G protein-gated inwardly rectifying K+ (GIRK) channels are key to stabilize NPY/AgRP neurons and that NPY/AgRP neuron-selective deletion of the GIRK2 subunit results in a persistently increased excitability of the NPY/AgRP neurons. Interestingly, increased body weight and adiposity observed in the NPY/AgRP neuron-selective GIRK2 knockout mice were due to decreased sympathetic activity and EE, while food intake remained unchanged. The conditional knockout mice also showed compromised adaptation to coldness. In summary, our study identified GIRK2 as a key determinant of NPY/AgRP neuronal excitability and driver of EE in physiological and stress conditions.
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Albers, H. E., J. E. Ottenweller, S. Y. Liou, M. D. Lumpkin, and E. R. Anderson. "Neuropeptide Y in the hypothalamus: effect on corticosterone and single-unit activity." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 258, no. 2 (1990): R376—R382. http://dx.doi.org/10.1152/ajpregu.1990.258.2.r376.
Testo completoAbstract (sommario):
The purpose of the present study was to determine whether neuropeptide Y (NPY) acts within the hypothalamic paraventricular nucleus (PVN) or the suprachiasmatic nucleus (SCN) to alter circulating levels of corticosterone and to evaluate the effects of NPY on the single-unit response of PVN and SCN neurons using the hypothalamic slice preparation. Blood levels of corticosterone were determined in groups of rats that received microinjections of NPY or saline (Sal) into the PVN or SCN. NPY injected into the PVN 4 h after light onset resulted in corticosterone levels of 13.15 +/- 2.18 (SE) micrograms/dl within 1 h, which were significantly higher than the corticosterone levels of 4.08 +/- 1.78 micrograms/dl seen in rats receiving Sal injections. In contrast, no significant differences were observed in circulating levels of corticosterone between groups of rats 1 or 4 h after NPY or Sal microinjection into the SCN. In the hypothalamic slice, NPY was found to produce primarily inhibitory responses in both SCN and PVN neurons. Forty-nine percent of the SCN units examined were inhibited. In addition, another 20% of the neurons tested in the SCN displayed excitation followed by more sustained inhibition. In the PVN, 45% of the units examined were inhibited by NPY, however, nearly 30% of the remaining neurons were significantly excited by NPY. In summary, NPY alters the electrical activity of both SCN and PVN neurons but appears to act only within the PVN to influence circulating levels of corticosterone. These and other data indicate that NPY acts as an important neurochemical messenger within several hypothalamic sites.
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Dimitrov, Eugene L., M. Regina DeJoseph, Mark S. Brownfield, and Janice H. Urban. "Involvement of Neuropeptide Y Y1 Receptors in the Regulation of Neuroendocrine Corticotropin-Releasing Hormone Neuronal Activity." Endocrinology 148, no. 8 (2007): 3666–73. http://dx.doi.org/10.1210/en.2006-1730.
Testo completoAbstract (sommario):
The neuroendocrine parvocellular CRH neurons in the paraventricular nucleus (PVN) of the hypothalamus are the main integrators of neural inputs that initiate hypothalamic-pituitary-adrenal (HPA) axis activation. Neuropeptide Y (NPY) expression is prominent within the PVN, and previous reports indicated that NPY stimulates CRH mRNA levels. The purpose of these studies was to examine the participation of NPY receptors in HPA axis activation and determine whether neuroendocrine CRH neurons express NPY receptor immunoreactivity. Infusion of 0.5 nmol NPY into the third ventricle increased plasma corticosterone levels in conscious rats, with the peak of hormone levels occurring 30 min after injection. This increase was prevented by pretreatment with the Y1 receptor antagonist BIBP3226. Immunohistochemistry showed that CRH-immunoreactive neurons coexpressed Y1 receptor immunoreactivity (Y1r-ir) in the PVN, and a majority of these neurons (88.8%) were neuroendocrine as determined by ip injections of FluoroGold. Bilateral infusion of the Y1/Y5 agonist, [leu31pro34]NPY (110 pmol), into the PVN increased c-Fos and phosphorylated cAMP response element-binding protein expression and elevated plasma corticosterone levels. Increased expression of c-Fos and phosphorylated cAMP response element-binding protein was observed in populations of CRH/Y1r-ir cells. The current findings present a comprehensive study of NPY Y1 receptor distribution and activation with respect to CRH neurons in the PVN. The expression of NPY Y1r-ir by neuroendocrine CRH cells suggests that alterations in NPY release and subsequent activation of NPY Y1 receptors plays an important role in the regulation of the HPA.
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Clark, Courtney M., Rosemary M. Clark, Joshua A. Hoyle, Jyoti A. Chuckowree, Catriona A. McLean, and Tracey C. Dickson. "Differential NPY-Y1 Receptor Density in the Motor Cortex of ALS Patients and Familial Model of ALS." Brain Sciences 11, no. 8 (2021): 969. http://dx.doi.org/10.3390/brainsci11080969.
Testo completoAbstract (sommario):
Destabilization of faciliatory and inhibitory circuits is an important feature of corticomotor pathology in amyotrophic lateral sclerosis (ALS). While GABAergic inputs to upper motor neurons are reduced in models of the disease, less understood is the involvement of peptidergic inputs to upper motor neurons in ALS. The neuropeptide Y (NPY) system has been shown to confer neuroprotection against numerous pathogenic mechanisms implicated in ALS. However, little is known about how the NPY system functions in the motor system. Herein, we investigate post-synaptic NPY signaling on upper motor neurons in the rodent and human motor cortex, and on cortical neuron populations in vitro. Using immunohistochemistry, we show the increased density of NPY-Y1 receptors on the soma of SMI32-positive upper motor neurons in post-mortem ALS cases and SOD1G93A excitatory cortical neurons in vitro. Analysis of receptor density on Thy1-YFP-H-positive upper motor neurons in wild-type and SOD1G93A mouse tissue revealed that the distribution of NPY-Y1 receptors was changed on the apical processes at early-symptomatic and late-symptomatic disease stages. Together, our data demonstrate the differential density of NPY-Y1 receptors on upper motor neurons in a familial model of ALS and in ALS cases, indicating a novel pathway that may be targeted to modulate upper motor neuron activity.