Articoli di riviste sul tema "Activité axonale"
Segui questo link per vedere altri tipi di pubblicazioni sul tema: Activité axonale.
Cita una fonte nei formati APA, MLA, Chicago, Harvard e in molti altri stili
Vedi i top-50 articoli di riviste per l'attività di ricerca sul tema "Activité axonale".
Accanto a ogni fonte nell'elenco di riferimenti c'è un pulsante "Aggiungi alla bibliografia". Premilo e genereremo automaticamente la citazione bibliografica dell'opera scelta nello stile citazionale di cui hai bisogno: APA, MLA, Harvard, Chicago, Vancouver ecc.
Puoi anche scaricare il testo completo della pubblicazione scientifica nel formato .pdf e leggere online l'abstract (il sommario) dell'opera se è presente nei metadati.
Vedi gli articoli di riviste di molte aree scientifiche e compila una bibliografia corretta.
1
Satkeviciute, Ieva, George Goodwin, Geoffrey M. Bove e Andrew Dilley. "Time course of ongoing activity during neuritis and following axonal transport disruption". Journal of Neurophysiology 119, n. 5 (1 maggio 2018): 1993–2000. http://dx.doi.org/10.1152/jn.00882.2017.
Abstract (sommario):
Local nerve inflammation (neuritis) leads to ongoing activity and axonal mechanical sensitivity (AMS) along intact nociceptor axons and disrupts axonal transport. This phenomenon forms the most feasible cause of radiating pain, such as sciatica. We have previously shown that axonal transport disruption without inflammation or degeneration also leads to AMS but does not cause ongoing activity at the time point when AMS occurs, despite causing cutaneous hypersensitivity. However, there have been no systematic studies of ongoing activity during neuritis or noninflammatory axonal transport disruption. In this study, we present the time course of ongoing activity from primary sensory neurons following neuritis and vinblastine-induced axonal transport disruption. Whereas 24% of C/slow Aδ-fiber neurons had ongoing activity during neuritis, few (<10%) A- and C-fiber neurons showed ongoing activity 1–15 days following vinblastine treatment. In contrast, AMS increased transiently at the vinblastine treatment site, peaking on days 4–5 (28% of C/slow Aδ-fiber neurons) and resolved by day 15. Conduction velocities were slowed in all groups. In summary, the disruption of axonal transport without inflammation does not lead to ongoing activity in sensory neurons, including nociceptors, but does cause a rapid and transient development of AMS. Because it is proposed that AMS underlies mechanically induced radiating pain, and a transient disruption of axonal transport (as previously reported) leads to transient AMS, it follows that processes that disrupt axonal transport, such as neuritis, must persist to maintain AMS and the associated symptoms. NEW & NOTEWORTHY Many patients with radiating pain lack signs of nerve injury on clinical examination but may have neuritis, which disrupts axonal transport. We have shown that axonal transport disruption does not induce ongoing activity in primary sensory neurons but does cause transient axonal mechanical sensitivity. The present data complete a profile of key axonal sensitivities following axonal transport disruption. Collectively, this profile supports that an active peripheral process is necessary for maintained axonal sensitivities.
2
Wang, Jack T., Zachary A. Medress, Mauricio E. Vargas e Ben A. Barres. "Local axonal protection by WldS as revealed by conditional regulation of protein stability". Proceedings of the National Academy of Sciences 112, n. 33 (24 luglio 2015): 10093–100. http://dx.doi.org/10.1073/pnas.1508337112.
Abstract (sommario):
The expression of the mutant Wallerian degeneration slow (WldS) protein significantly delays axonal degeneration from various nerve injuries and in multiple species; however, the mechanism for its axonal protective property remains unclear. Although WldS is localized predominantly in the nucleus, it also is present in a smaller axonal pool, leading to conflicting models to account for the WldS fraction necessary for axonal protection. To identify where WldS activity is required to delay axonal degeneration, we adopted a method to alter the temporal expression of WldS protein in neurons by chemically regulating its protein stability. We demonstrate that continuous WldS activity in the axonal compartment is both necessary and sufficient to delay axonal degeneration. Furthermore, by specifically increasing axonal WldS expression postaxotomy, we reveal a critical period of 4–5 h postinjury during which the course of Wallerian axonal degeneration can be halted. Finally, we show that NAD+, the metabolite of WldS/nicotinamide mononucleotide adenylyltransferase enzymatic activity, is sufficient and specific to confer WldS-like axon protection and is a likely molecular mediator of WldS axon protection. The results delineate a therapeutic window in which the course of Wallerian degeneration can be delayed even after injures have occurred and help narrow the molecular targets of WldS activity to events within the axonal compartment.
3
Chen, Yanmin, e Zu-Hang Sheng. "Kinesin-1–syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport". Journal of Cell Biology 202, n. 2 (15 luglio 2013): 351–64. http://dx.doi.org/10.1083/jcb.201302040.
Abstract (sommario):
Axonal mitochondria are recruited to synaptic terminals in response to neuronal activity, but the mechanisms underlying activity-dependent regulation of mitochondrial transport are largely unknown. In this paper, using genetic mouse model combined with live imaging, we demonstrate that syntaphilin (SNPH) mediates the activity-dependent immobilization of axonal mitochondria through binding to KIF5. In vitro analysis showed that the KIF5–SNPH coupling inhibited the motor adenosine triphosphatase. Neuronal activity further recruited SNPH to axonal mitochondria. This motor-docking interplay was induced by Ca2+ and synaptic activity and was necessary to establish an appropriate balance between motile and stationary axonal mitochondria. Deleting snph abolished the activity-dependent immobilization of axonal mitochondria. We propose an “Engine-Switch and Brake” model, in which SNPH acts both as an engine off switch by sensing mitochondrial Rho guanosine triphosphatase-Ca2+ and as a brake by anchoring mitochondria to the microtubule track. Altogether, our study provides new mechanistic insight into the molecular interplay between motor and docking proteins, which arrests axonal mitochondrial transport in response to changes in neuronal activity.
4
Tang, Bor. "Why is NMNAT Protective against Neuronal Cell Death and Axon Degeneration, but Inhibitory of Axon Regeneration?" Cells 8, n. 3 (21 marzo 2019): 267. http://dx.doi.org/10.3390/cells8030267.
Abstract (sommario):
Nicotinamide mononucleotide adenylyltransferase (NMNAT), a key enzyme for NAD+ synthesis, is well known for its activity in neuronal survival and attenuation of Wallerian degeneration. Recent investigations in invertebrate models have, however, revealed that NMNAT activity negatively impacts upon axon regeneration. Overexpression of Nmnat in laser-severed Drosophila sensory neurons reduced axon regeneration, while axon regeneration was enhanced in injured mechanosensory axons in C. elegans nmat-2 null mutants. These diametrically opposite effects of NMNAT orthologues on neuroprotection and axon regeneration appear counterintuitive as there are many examples of neuroprotective factors that also promote neurite outgrowth, and enhanced neuronal survival would logically facilitate regeneration. We suggest here that while NMNAT activity and NAD+ production activate neuroprotective mechanisms such as SIRT1-mediated deacetylation, the same mechanisms may also activate a key axonal regeneration inhibitor, namely phosphatase and tensin homolog (PTEN). SIRT1 is known to deacetylate and activate PTEN which could, in turn, suppress PI3 kinase–mTORC1-mediated induction of localized axonal protein translation, an important process that determines successful regeneration. Strategic tuning of Nmnat activity and NAD+ production in axotomized neurons may thus be necessary to promote initial survival without inhibiting subsequent regeneration.
5
Corna, Andrea, Timo Lausen, Roland Thewes e Günther Zeck. "Electrical imaging of axonal stimulation in the retina". Current Directions in Biomedical Engineering 8, n. 3 (1 settembre 2022): 33–36. http://dx.doi.org/10.1515/cdbme-2022-2009.
Abstract (sommario):
Abstract Stimulation of axons or its avoidance plays a central role for neuroprosthetics and neural-interfaces research. One peculiar example constitutes retinal implants. Retinal implants aim to artificially activate retinal ganglion cells (RGCs) via electrical stimulation. Such stimulation, however, often generates undesired stimulation of RGC axon bundles, which leads to distorted visual percepts. In order to establish stimulation strategies avoiding axonal stimulation it is necessary to image the evoked activity in single axons. In this work we electrically imaged axonal stimulation in ex vivo mouse retina using a high-density CMOS-based microelectrode array. We demonstrate signal propagation tracking via stimulus triggered average during high frequency (100 Hz) sinusoidal electrical stimulation.
6
Tigerholm, Jenny, Marcus E. Petersson, Otilia Obreja, Angelika Lampert, Richard Carr, Martin Schmelz e Erik Fransén. "Modeling activity-dependent changes of axonal spike conduction in primary afferent C-nociceptors". Journal of Neurophysiology 111, n. 9 (1 maggio 2014): 1721–35. http://dx.doi.org/10.1152/jn.00777.2012.
Abstract (sommario):
Action potential initiation and conduction along peripheral axons is a dynamic process that displays pronounced activity dependence. In patients with neuropathic pain, differences in the modulation of axonal conduction velocity by activity suggest that this property may provide insight into some of the pathomechanisms. To date, direct recordings of axonal membrane potential have been hampered by the small diameter of the fibers. We have therefore adopted an alternative approach to examine the basis of activity-dependent changes in axonal conduction by constructing a comprehensive mathematical model of human cutaneous C-fibers. Our model reproduced axonal spike propagation at a velocity of 0.69 m/s commensurate with recordings from human C-nociceptors. Activity-dependent slowing (ADS) of axonal propagation velocity was adequately simulated by the model. Interestingly, the property most readily associated with ADS was an increase in the concentration of intra-axonal sodium. This affected the driving potential of sodium currents, thereby producing latency changes comparable to those observed for experimental ADS. The model also adequately reproduced post-action potential excitability changes (i.e., recovery cycles) observed in vivo. We performed a series of control experiments replicating blockade of particular ion channels as well as changing temperature and extracellular ion concentrations. In the absence of direct experimental approaches, the model allows specific hypotheses to be formulated regarding the mechanisms underlying activity-dependent changes in C-fiber conduction. Because ADS might functionally act as a negative feedback to limit trains of nociceptor activity, we envisage that identifying its mechanisms may also direct efforts aimed at alleviating neuronal hyperexcitability in pain patients.
7
Hwang, Jinyeon, e Uk Namgung. "Phosphorylation of STAT3 by axonal Cdk5 promotes axonal regeneration by modulating mitochondrial activity". Experimental Neurology 335 (gennaio 2021): 113511. http://dx.doi.org/10.1016/j.expneurol.2020.113511.
8
Jamann, Nora, Merryn Jordan e Maren Engelhardt. "Activity-Dependent Axonal Plasticity in Sensory Systems". Neuroscience 368 (gennaio 2018): 268–82. http://dx.doi.org/10.1016/j.neuroscience.2017.07.035.
9
Susuki, Keiichiro, e Hiroshi Kuba. "Activity-dependent regulation of excitable axonal domains". Journal of Physiological Sciences 66, n. 2 (13 ottobre 2015): 99–104. http://dx.doi.org/10.1007/s12576-015-0413-4.
10
Ganguly, Archan, Xuemei Han, Utpal Das, Lina Wang, Jonathan Loi, Jichao Sun, Daniel Gitler et al. "Hsc70 chaperone activity is required for the cytosolic slow axonal transport of synapsin". Journal of Cell Biology 216, n. 7 (30 maggio 2017): 2059–74. http://dx.doi.org/10.1083/jcb.201604028.
Abstract (sommario):
Soluble cytosolic proteins vital to axonal and presynaptic function are synthesized in the neuronal soma and conveyed via slow axonal transport. Our previous studies suggest that the overall slow transport of synapsin is mediated by dynamic assembly/disassembly of cargo complexes followed by short-range vectorial transit (the “dynamic recruitment” model). However, neither the composition of these complexes nor the mechanistic basis for the dynamic behavior is understood. In this study, we first examined putative cargo complexes associated with synapsin using coimmunoprecipitation and multidimensional protein identification technology mass spectrometry (MS). MS data indicate that synapsin is part of a multiprotein complex enriched in chaperones/cochaperones including Hsc70. Axonal synapsin–Hsc70 coclusters are also visualized by two-color superresolution microscopy. Inhibition of Hsc70 ATPase activity blocked the slow transport of synapsin, disrupted axonal synapsin organization, and attenuated Hsc70–synapsin associations, advocating a model where Hsc70 activity dynamically clusters cytosolic proteins into cargo complexes, allowing transport. Collectively, our study offers insight into the molecular organization of cytosolic transport complexes and identifies a novel regulator of slow transport.
11
Spector, J. Gershon, e Patty Lee. "Axonal Regeneration in Severed Peripheral Facial Nerve of the Rabbit: Relation of the Number of Axonal Regenerates to Behavioral and Evoked Muscle Activity". Annals of Otology, Rhinology & Laryngology 107, n. 2 (febbraio 1998): 141–48. http://dx.doi.org/10.1177/000348949810700210.
Abstract (sommario):
The minimum number of regenerating facial nerve myelinated motor axons that are required to innervate and activate the mimetic musculature is not known. We compare rabbit facial nerve regeneration following complete transectional injuries of the buccal division to the evoked and behavioral muscle activities of the quadratus labii superioris muscle of the rabbit in three experimental models: end-to-end direct anastomosis (N = 4), 8-mm autologous nerve grafts (N = 8), and 10-mm silicone chamber implants (N = 40). Data are presented as total numbers of regenerating myelinated axons that traverse the surgical repair and innervate the fascicles of the transected distal nerve stump, as well as the percentage of regenerating neurites, as compared to the preoperative normal controls. Five weeks after neural repair, direct end-to-end anastomosis regained more myelinated axons across the reconstructed defect (2,632 × 1,232; 67%) than silicone tube implants (2,006 × 445; 51%) or autologous cable graft repairs (1,660 × 1,169; 42%). However, only a small percentage of myelinated fibers innervated the intrafascicular region of the distal transected neural stump in direct anastomosis (948 × 168; 24%), silicone tube implants (670 × 275; 17%), or autologous nerve grafts (445 × 120; 12%) in rabbits that regained evoked and behavioral mimetic muscle activity. All rabbits with direct anastomosis and neural cable grafts regained motor activity, despite the fact that 66% of regenerating motor neurites in cable graft repairs and 54% in direct anastomosis were collateral sprouts that did not contribute to effective muscle activity. In 17 rabbits with neural regenerates within the silicone tube implants that did not regain mimetic activity, the mean number of regenerating myelinated motor axons across the defect was 504 × 419 (13%), and the mean number of axons that innervated the distal transected nerve stump fascicles was 277 × 128 (7%). Therefore, the minimal number of motor axons that is required to activate the quadratus labii superioris muscle is 12% of the original motor axon population of the normal buccal nerve division.
12
Buccino, Alessio Paolo, Xinyue Yuan, Vishalini Emmenegger, Xiaohan Xue, Tobias Gänswein e Andreas Hierlemann. "An automated method for precise axon reconstruction from recordings of high-density micro-electrode arrays". Journal of Neural Engineering 19, n. 2 (31 marzo 2022): 026026. http://dx.doi.org/10.1088/1741-2552/ac59a2.
Abstract (sommario):
Abstract Objective: Neurons communicate with each other by sending action potentials (APs) through their axons. The velocity of axonal signal propagation describes how fast electrical APs can travel. This velocity can be affected in a human brain by several pathologies, including multiple sclerosis, traumatic brain injury and channelopathies. High-density microelectrode arrays (HD-MEAs) provide unprecedented spatio-temporal resolution to extracellularly record neural electrical activity. The high density of the recording electrodes enables to image the activity of individual neurons down to subcellular resolution, which includes the propagation of axonal signals. However, axon reconstruction, to date, mainly relies on manual approaches to select the electrodes and channels that seemingly record the signals along a specific axon, while an automated approach to track multiple axonal branches in extracellular action-potential recordings is still missing. Approach: In this article, we propose a fully automated approach to reconstruct axons from extracellular electrical-potential landscapes, so-called ‘electrical footprints’ of neurons. After an initial electrode and channel selection, the proposed method first constructs a graph based on the voltage signal amplitudes and latencies. Then, the graph is interrogated to extract possible axonal branches. Finally, the axonal branches are pruned, and axonal action-potential propagation velocities are computed. Main results: We first validate our method using simulated data from detailed reconstructions of neurons, showing that our approach is capable of accurately reconstructing axonal branches. We then apply the reconstruction algorithm to experimental recordings of HD-MEAs and show that it can be used to determine axonal morphologies and signal-propagation velocities at high throughput. Significance: We introduce a fully automated method to reconstruct axonal branches and estimate axonal action-potential propagation velocities using HD-MEA recordings. Our method yields highly reliable and reproducible velocity estimations, which constitute an important electrophysiological feature of neuronal preparations.
13
Vossel, Keith A., Jordan C. Xu, Vira Fomenko, Takashi Miyamoto, Elsa Suberbielle, Joseph A. Knox, Kaitlyn Ho, Daniel H. Kim, Gui-Qiu Yu e Lennart Mucke. "Tau reduction prevents Aβ-induced axonal transport deficits by blocking activation of GSK3β". Journal of Cell Biology 209, n. 3 (11 maggio 2015): 419–33. http://dx.doi.org/10.1083/jcb.201407065.
Abstract (sommario):
Axonal transport deficits in Alzheimer’s disease (AD) are attributed to amyloid β (Aβ) peptides and pathological forms of the microtubule-associated protein tau. Genetic ablation of tau prevents neuronal overexcitation and axonal transport deficits caused by recombinant Aβ oligomers. Relevance of these findings to naturally secreted Aβ and mechanisms underlying tau’s enabling effect are unknown. Here we demonstrate deficits in anterograde axonal transport of mitochondria in primary neurons from transgenic mice expressing familial AD-linked forms of human amyloid precursor protein. We show that these deficits depend on Aβ1–42 production and are prevented by tau reduction. The copathogenic effect of tau did not depend on its microtubule binding, interactions with Fyn, or potential role in neuronal development. Inhibition of neuronal activity, N-methyl-d-aspartate receptor function, or glycogen synthase kinase 3β (GSK3β) activity or expression also abolished Aβ-induced transport deficits. Tau ablation prevented Aβ-induced GSK3β activation. Thus, tau allows Aβ oligomers to inhibit axonal transport through activation of GSK3β, possibly by facilitating aberrant neuronal activity.
14
Steers, W. D., B. Mallory e W. C. de Groat. "Electrophysiological study of neural activity in penile nerve of the rat". American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 254, n. 6 (1 giugno 1988): R989—R1000. http://dx.doi.org/10.1152/ajpregu.1988.254.6.r989.
Abstract (sommario):
Electrophysiological techniques were used to examine the axonal composition and reflex activity of the penile nerve of the rat. Stimulation of either the pelvic nerve, hypogastric nerve, or sympathetic chain elicited synaptic and axonal volleys in the penile nerve. Synaptic responses were suppressed by nicotinic ganglionic blockade, indicating that they were mediated by cholinergic transmission in peripheral ganglia. Axonal volleys represented in part afferent pathways from receptors in the pelvic muscles, perineum, and anus. Stimulation of the penile or pelvic nerves increased intracavernous pressure. Stimulation of the dorsal nerve of the penis elicited central reflexes (50- to 150-ms latencies) in the penile nerve. Those reflexes were not eliminated by acute or chronic spinalization (T8) but were abolished by transection of preganglionic nerves, indicating an origin in the lumbosacral spinal cord. Thus the penile nerves are composed of a heterogenous population of afferent and efferent axons. Reflex activity elicited in these nerves by stimulation of pathways from the penis is probably involved in the initiation of penile erection.
15
Da Silva, Jorge Santos, Takafumi Hasegawa, Taeko Miyagi, Carlos G. Dotti e Jose Abad-Rodriguez. "Asymmetric membrane ganglioside sialidase activity specifies axonal fate". Nature Neuroscience 8, n. 5 (17 aprile 2005): 606–15. http://dx.doi.org/10.1038/nn1442.
16
Tao, Kentaro, Norio Matsuki e Ryuta Koyama. "Activity-dependent dynamics of mitochondria regulates axonal morphogenesis". Neuroscience Research 68 (gennaio 2010): e139. http://dx.doi.org/10.1016/j.neures.2010.07.2188.
17
Hammerschlag, Richard, e Judy Bobinski. "Does nerve impulse activity modulate fast axonal transport?" Molecular Neurobiology 6, n. 2-3 (giugno 1992): 191–201. http://dx.doi.org/10.1007/bf02780552.
18
Korhonen, Laura, e Dan Lindholm. "The ubiquitin proteasome system in synaptic and axonal degeneration". Journal of Cell Biology 165, n. 1 (5 aprile 2004): 27–30. http://dx.doi.org/10.1083/jcb.200311091.
Abstract (sommario):
The ubiquitin proteasome system (UPS) contributes to the pathophysiology of neurodegenerative diseases, and it is also a major determinant of synaptic protein degradation and activity. Recent studies in rodents and in the fruit fly Drosophila have shown that the activity of the UPS is involved in axonal degeneration. Increased knowledge of the UPS in synaptic and axonal reactions may provide novel drug targets for treatments of neuronal injuries and neurodegenerative disorders.
19
Losurdo, Michela, Johan Davidsson e Mattias K. Sköld. "Diffuse Axonal Injury in the Rat Brain: Axonal Injury and Oligodendrocyte Activity Following Rotational Injury". Brain Sciences 10, n. 4 (10 aprile 2020): 229. http://dx.doi.org/10.3390/brainsci10040229.
Abstract (sommario):
Traumatic brain injury (TBI) commonly results in primary diffuse axonal injury (DAI) and associated secondary injuries that evolve through a cascade of pathological mechanisms. We aim at assessing how myelin and oligodendrocytes react to head angular-acceleration-induced TBI in a previously described model. This model induces axonal injuries visible by amyloid precursor protein (APP) expression, predominantly in the corpus callosum and its borders. Brain tissue from a total of 27 adult rats was collected at 24 h, 72 h and 7 d post-injury. Coronal sections were prepared for immunohistochemistry and RNAscope® to investigate DAI and myelin changes (APP, MBP, Rip), oligodendrocyte lineage cell loss (Olig2), oligodendrocyte progenitor cells (OPCs) (NG2, PDGFRa) and neuronal stress (HSP70, ATF3). Oligodendrocytes and OPCs numbers (expressed as percentage of positive cells out of total number of cells) were measured in areas with high APP expression. Results showed non-statistically significant trends with a decrease in oligodendrocyte lineage cells and an increase in OPCs. Levels of myelination were mostly unaltered, although Rip expression differed significantly between sham and injured animals in the frontal brain. Neuronal stress markers were induced at the dorsal cortex and habenular nuclei. We conclude that rotational injury induces DAI and neuronal stress in specific areas. We noticed indications of oligodendrocyte death and regeneration without statistically significant changes at the timepoints measured, despite indications of axonal injuries and neuronal stress. This might suggest that oligodendrocytes are robust enough to withstand this kind of trauma, knowledge important for the understanding of thresholds for cell injury and post-traumatic recovery potential.
20
Williams, Emma-Jane, Frank S. Walsh e Patrick Doherty. "The FGF receptor uses the endocannabinoid signaling system to couple to an axonal growth response". Journal of Cell Biology 160, n. 4 (10 febbraio 2003): 481–86. http://dx.doi.org/10.1083/jcb.200210164.
Abstract (sommario):
Akey role for DAG lipase activity in the control of axonal growth and guidance in vitro and in vivo has been established. For example, DAG lipase activity is required for FGF-stimulated calcium influx into neuronal growth cones, and this response is both necessary and sufficient for an axonal growth response. The mechanism that couples the hydrolysis of DAG to the calcium response is not known. The initial hydrolysis of DAG at the sn-1 position (by DAG lipase) will generate 2-arachidonylglycerol, and this molecule is well established as an endogenous cannabinoid receptor agonist in the brain. In the present paper, we show that in rat cerebellar granule neurons, CB1 cannabinoid receptor antagonists inhibit axonal growth responses stimulated by N-cadherin and FGF2. Furthermore, three CB1 receptor agonists mimic the N-cadherin/FGF2 response at a step downstream from FGF receptor activation, but upstream from calcium influx into cells. In contrast, we could find no evidence for the CB1 receptor coupling the TrkB neurotrophin receptor to an axonal growth response in the same neurons. The observation that the CB1 receptor can couple the activated FGF receptor to an axonal growth response raises novel therapeutic opportunities.
21
Pigino, G., G. Paglini, L. Ulloa, J. Avila e A. Caceres. "Analysis of the expression, distribution and function of cyclin dependent kinase 5 (cdk5) in developing cerebellar macroneurons". Journal of Cell Science 110, n. 2 (15 gennaio 1997): 257–70. http://dx.doi.org/10.1242/jcs.110.2.257.
Abstract (sommario):
Cultures of cerebellar macroneurons were used to study the expression, activity, subcellular localization, and function of cdk5 during neuronal morphogenesis. The results obtained indicate that in non-polarized neurons cdk5 is restricted to the cell body but as soon as polarity is established it becomes highly concentrated at the distal tip of growing axons where it associates with microtubules and the subcortical cytoskeleton. In addition, we show that laminin, an extracellular matrix molecule capable of stimulating axonal extension and promoting MAP1b phosphorylation (DiTella et al., 1996), accelerates the redistribution of cdk5 to the axonal tip and dramatically increases its activity. Finally, our results indicate that cdk5 suppression by antisense oligonucleotide treatment selectively reduces axonal elongation and decreases the phosphorylation status of MAP1b, as well as its binding to microtubules. Taken collectively, our observations suggest that cdk5 may serve as an important regulatory linker between environmental signals (e.g. laminin) and constituents of the intracellular machinery (e.g. MAP1b) involved in axonal formation.
22
Christie, Jason M., e Craig E. Jahr. "Dendritic NMDA Receptors Activate Axonal Calcium Channels". Neuron 60, n. 2 (ottobre 2008): 298–307. http://dx.doi.org/10.1016/j.neuron.2008.08.028.
23
Verbny, Yakov, Chuan-Li Zhang e Shing Yan Chiu. "Coupling of Calcium Homeostasis to Axonal Sodium in Axons of Mouse Optic Nerve". Journal of Neurophysiology 88, n. 2 (1 agosto 2002): 802–16. http://dx.doi.org/10.1152/jn.2002.88.2.802.
Abstract (sommario):
Axonal populations in neonatal and mature optic nerves were selectively stained with calcium dyes for analysis of calcium homeostasis and its possible coupling to axonal Na. Repetitive nerve stimulation causes a rise in axonal [Ca2+]i the posttetanus recovery of which is impeded by increasing the number of action potentials in the tetanus. This effect is augmented in 4-aminopyridine (4-AP; 1 mM), which dramatically increases the calcium and presumably sodium load during the tetanus. Increasing axonal [Na]i with the Na-ionophore monensin (4–50 μM) and ouabain (30 μM) retards posttetanus calcium decline, suggesting that efficient calcium clearance depends on a low level of axonal [Na]i. Posttetanus calcium clearance is not affected by K-mediated depolarization. To further examine coupling between axonal [Na]i and [Ca2+]i, the resting axonal [Ca2+]i was monitored as axonal [Na+]i was elevated with ouabain, veratridine, and monensin. In all cases, elevation of axonal [Na+]i evokes a calcium influx into axons. This influx is unrelated to activation of calcium channels but is consistent with calcium influx via reversal of the Na/Ca exchanger expected as a consequence of axonal [Na+]i elevation. In conclusion, this study demonstrates that calcium homeostasis in the axons of the optic nerve is strongly coupled to axonal [Na+]i in a manner consistent with the Na/Ca exchanger playing a major role in extruding calcium following nerve activity.
24
Zorrilla de San Martin, Javier, Abdelali Jalil e Federico F. Trigo. "Impact of single-site axonal GABAergic synaptic events on cerebellar interneuron activity". Journal of General Physiology 146, n. 6 (30 novembre 2015): 477–93. http://dx.doi.org/10.1085/jgp.201511506.
Abstract (sommario):
Axonal ionotropic receptors are present in a variety of neuronal types, and their function has largely been associated with the modulation of axonal activity and synaptic release. It is usually assumed that activation of axonal GABAARs comes from spillover, but in cerebellar molecular layer interneurons (MLIs) the GABA source is different: in these cells, GABA release activates presynaptic GABAA autoreceptors (autoRs) together with postsynaptic targets, producing an autoR-mediated synaptic event. The frequency of presynaptic, autoR-mediated miniature currents is twice that of their somatodendritic counterparts, suggesting that autoR-mediated responses have an important effect on interneuron activity. Here, we used local Ca2+ photolysis in MLI axons of juvenile rats to evoke GABA release from individual varicosities to study the activation of axonal autoRs in single release sites. Our data show that single-site autoR conductances are similar to postsynaptic dendritic conductances. In conditions of high [Cl−]i, autoR-mediated conductances range from 1 to 5 nS; this corresponds to ∼30–150 GABAA channels per presynaptic varicosity, a value close to the number of channels in postsynaptic densities. Voltage responses produced by the activation of autoRs in single varicosities are amplified by a Nav-dependent mechanism and propagate along the axon with a length constant of 91 µm. Immunolabeling determination of synapse location shows that on average, one third of the synapses produce autoR-mediated signals that are large enough to reach the axon initial segment. Finally, we show that single-site activation of presynaptic GABAA autoRs leads to an increase in MLI excitability and thus conveys a strong feedback signal that contributes to spiking activity.
25
Chen, Jieli, Alex Zacharek, Xu Cui, Amjad Shehadah, Hao Jiang, Cynthia Roberts, Mei Lu e Michael Chopp. "Treatment of Stroke with a Synthetic Liver X Receptor Agonist, TO901317, Promotes Synaptic Plasticity and Axonal Regeneration in Mice". Journal of Cerebral Blood Flow & Metabolism 30, n. 1 (2 settembre 2009): 102–9. http://dx.doi.org/10.1038/jcbfm.2009.187.
Abstract (sommario):
In this study, we tested the hypothesis that TO901317 promotes synapse plasticity and axonal regeneration after stroke. Adult male C57BL/6J mice were subjected to middle cerebral artery occlusion (MCAo) and treated with or without TO901317 starting 24 h after MCAo daily for 14 days. Axonal damage and regeneration were evaluated by immunostaining. TO901317 significantly increased synaptophysin expression and axonal regeneration, as well as decreased the expressions of amyloid betaA4 precursor protein and Nogo receptor (NgR) in the ischemic brain. To test whether TO901317 regulates the phosphorylation of phosphatidylinositol 3-kinase (p-PI3K) and Akt (p-Akt) activity in the ischemic brain, MCAo mice were treated with or without TO901317 starting 24 h after MCAo daily for 4 days and were then killed at 5 days after MCAo. TO901317 treatment significantly increased p-PI3K and p-Akt activity, but did not increase total PI3K expression in the ischemic brain. Using primary cortical neuron (PCN) culture, TO901317 significantly increased synaptophysin expression, p-PI3K activity, and decreased NgR expression compared with nontreated controls. TO901317 also significantly increased neurite outgrowth, and inhibition of the PI3K/Akt pathway by LY294002 decreased neurite outgrowth in both controls and TO901317-treated groups in cultured hypoxic PCN. These data indicate that TO901317 promotes synaptic plasticity and axonal regeneration, and that PI3K/Akt signaling activity contributes to neurite outgrowth.
26
Benes, Jessica A., Kylie N. House, Frank N. Burks, Kris P. Conaway, Donald P. Julien, Jeffrey P. Donley, Michael A. Iyamu e Andrew D. McClellan. "Regulation of axonal regeneration following spinal cord injury in the lamprey". Journal of Neurophysiology 118, n. 3 (1 settembre 2017): 1439–56. http://dx.doi.org/10.1152/jn.00986.2016.
Abstract (sommario):
Following rostral spinal cord injury (SCI) in larval lampreys, injured descending brain neurons, particularly reticulospinal (RS) neurons, regenerate their axons, and locomotor behavior recovers in a few weeks. However, axonal regeneration of descending brain neurons is mostly limited to relatively short distances, but the mechanisms for incomplete axonal regeneration are unclear. First, lampreys with rostral SCI exhibited greater axonal regeneration of descending brain neurons, including RS neurons, as well as more rapid recovery of locomotor muscle activity right below the lesion site, compared with animals with caudal SCI. In addition, following rostral SCI, most injured RS neurons displayed the “injury phenotype,” whereas following caudal SCI, most injured neurons displayed normal electrical properties. Second, following rostral SCI, at cold temperatures (~4–5°C), axonal transport was suppressed, axonal regeneration and behavioral recovery were blocked, and injured RS neurons displayed normal electrical properties. Cold temperatures appear to prevent injured RS neurons from detecting and/or responding to SCI. It is hypothesized that following rostral SCI, injured descending brain neurons are strongly stimulated to regenerate their axons, presumably because of elimination of spinal synapses and reduced neurotrophic support. However, when these neurons regenerate their axons and make synapses right below the lesion site, restoration of neurotrophic support very likely suppress further axonal regeneration. In contrast, caudal SCI is a weak stimulus for axonal regeneration, presumably because of spared synapses above the lesion site. These results may have implications for mammalian SCI, which can spare synapses above the lesion site for supraspinal descending neurons and propriospinal neurons. NEW & NOTEWORTHY Lampreys with rostral spinal cord injury (SCI) exhibited greater axonal regeneration of descending brain neurons and more rapid recovery of locomotor muscle activity below the lesion site compared with animals with caudal SCI. In addition, following rostral SCI, most injured reticulospinal (RS) neurons displayed the “injury phenotype,” whereas following caudal SCI, most injured neurons had normal electrical properties. We hypothesize that following caudal SCI, the spared synapses of injured RS neurons might limit axonal regeneration and behavioral recovery.
27
Gennarelli, T. A., L. E. Thibault, R. Tipperman, G. Tomei, R. Sergot, M. Brown, W. L. Maxwell et al. "Axonal injury in the optic nerve: a model simulating diffuse axonal injury in the brain". Journal of Neurosurgery 71, n. 2 (agosto 1989): 244–53. http://dx.doi.org/10.3171/jns.1989.71.2.0244.
Abstract (sommario):
✓ A new model of traumatic axonal injury has been developed by causing a single, rapid, controlled elongation (tensile strain) in the optic nerve of the albino guinea pig. Electron microscopy demonstrates axonal swelling, axolemmal blebs, and accumulation of organelles identical to those seen in human and experimental brain injury. Quantitative morphometric studies confirm that 17% of the optic nerve axons are injured without vascular disruption, and horseradish peroxidase (HRP) studies confirm alterations in rapid axoplasmic transport at the sites of injury. Since 95% to 98% of the optic nerve fibers are crossed, studies of the cell bodies and terminal fields of injured axons can be performed in this model. Glucose utilization was increased in the retina following injury, confirming electron microscopic changes of central chromatolysis in the ganglion cells and increased metabolic activity in reaction to axonal injury. Decreased activity at the superior colliculus was demonstrated by delayed HRP arrival after injury. The model is unique because it produces axonal damage that is morphologically identical to that seen in human brain injury and does so by delivering tissue strains of the same type and magnitude that cause axonal damage in the human. The model offers the possibility of improving the understanding of traumatic damage of central nervous system (CNS) axons because it creates reproducible axonal injury in a well-defined anatomical system that obviates many of the difficulties associated with studying the complex morphology of the brain.
28
Sala-Jarque, Julia, Francina Mesquida-Veny, Maider Badiola-Mateos, Josep Samitier, Arnau Hervera e José Antonio del Río. "Neuromuscular Activity Induces Paracrine Signaling and Triggers Axonal Regrowth after Injury in Microfluidic Lab-On-Chip Devices". Cells 9, n. 2 (27 gennaio 2020): 302. http://dx.doi.org/10.3390/cells9020302.
Abstract (sommario):
Peripheral nerve injuries, including motor neuron axonal injury, often lead to functional impairments. Current therapies are mostly limited to surgical intervention after lesion, yet these interventions have limited success in restoring functionality. Current activity-based therapies after axonal injuries are based on trial-error approaches in which the details of the underlying cellular and molecular processes are largely unknown. Here we show the effects of the modulation of both neuronal and muscular activity with optogenetic approaches to assess the regenerative capacity of cultured motor neuron (MN) after lesion in a compartmentalized microfluidic-assisted axotomy device. With increased neuronal activity, we observed an increase in the ratio of regrowing axons after injury in our peripheral-injury model. Moreover, increasing muscular activity induces the liberation of leukemia inhibitory factor and glial cell line-derived neurotrophic factor in a paracrine fashion that in turn triggers axonal regrowth of lesioned MN in our 3D hydrogel cultures. The relevance of our findings as well as the novel approaches used in this study could be useful not only after axotomy events but also in diseases affecting MN survival.
29
Parnas, I., G. Rashkovan, V. O'Connor, O. El-Far, H. Betz e H. Parnas. "Role of NSF in Neurotransmitter Release: A Peptide Microinjection Study at the Crayfish Neuromuscular Junction". Journal of Neurophysiology 96, n. 3 (settembre 2006): 1053–60. http://dx.doi.org/10.1152/jn.01313.2005.
Abstract (sommario):
Peptides that inhibit the SNAP-stimulated ATPase activity of N-ethylmaleimide-sensitive fusion protein (NSF-2, NSF-3) were injected intra-axonally to study the role of this protein in the release of glutamate at the crayfish neuromuscular junction. Macropatch recording was used to establish the quantal content and to construct synaptic delay histograms. NSF-2 or NSF-3 injection reduced the quantal content, evoked by either direct depolarization of a single release bouton or by axonal action potentials, on average by 66 ± 12% (mean ± SD; n = 32), but had no effect on the time course of release. NSF-2 had no effect on the amplitude or shape of the presynaptic action potential nor on the excitatory nerve terminal current. Neither NSF-2 nor NSF-3 affected the shape or amplitude of single quantal currents. Injection of a peptide with the same composition as NSF-2, but with a scrambled amino acid sequence, failed to alter the quantal content. We conclude that, at the crayfish neuromuscular junction, NSF-dependent reactions regulate quantal content without contributing to the presynaptic mechanisms that control the time course of release.
30
Morita, K., G. David, J. N. Barrett e E. F. Barrett. "Posttetanic hyperpolarization produced by electrogenic Na(+)-K+ pump in lizard axons impaled near their motor terminals". Journal of Neurophysiology 70, n. 5 (1 novembre 1993): 1874–84. http://dx.doi.org/10.1152/jn.1993.70.5.1874.
Abstract (sommario):
1. The hyperpolarization that follows tetanic stimulation was recorded intra-axonally from the internodal region of intramuscular myelinated motor axons. 2. The peak amplitude of the posttetanic hyperpolarization (PTH) that followed stimulation at 20-100 Hz for < or = 35 s increased with increasing train duration, reaching a maximum of 22 mV. PTH decayed over a time course that increased from tens to hundreds of seconds with increasing train duration. For a given frequency of stimulation the time integral of PTH was proportional to the number of stimuli in the train, averaging 3-4 mV.s per action potential. 3. Ouabain (0.1-1 mM) and cyanide (1 mM) depolarized the resting potential and abolished PTH. Tetanic stimulation in ouabain was followed by a slowly decaying depolarization (probably due to extra-axonal K+ accumulation) whose magnitude and duration increased as the duration of the train increased. 4. Axonal input resistance showed no consistent change during PTH in normal solution but increased during PTH in the presence of 3 mM Cs+ (which blocks axonal inward rectifier currents). 5. PTH was abolished when bath Na+ was replaced by Li+ or choline. PTH persisted after removal of bath Ca2+ and addition of 2 mM Mn2+. 6. Removal of bath K+ abolished the PTH recorded after brief stimulus trains and greatly reduced the duration of PTH recorded after longer stimulus trains. 7. A brief application of 10 mM K+, which normally depolarizes axons, produced a ouabain-sensitive hyperpolarization in axons bathed in K(+)-free solution. 8. These observations suggest that in these myelinated axons PTH is produced mainly by activation of an electrogenic Na(+)-K(+)-ATPase, rather than by changes in K+ permeability or transmembrane [K+] gradients. This conclusion is supported by calculations showing agreement between estimates of Na+ efflux/impulse based on PTH measurements and estimates of Na+ influx/impulse based on nodal voltage-clamp measurements. Pump activity also appears to contribute to the resting potential. 9. The stimulus intensity required to initiate a propagating action potential increased during PTH but decreased during the posttetanic depolarization recorded in ouabain. Thus changes in axonal excitability after tetanic stimulation correlate with changes in the posttetanic membrane potential. 10. Action potentials that propagated during PTH had a larger peak amplitude and were followed by a larger and longer depolarizing afterpotential than action potentials elicited at the resting potential. This enhancement of the depolarizing afterpotential is consistent with previous reports of an increased superexcitable period after action potentials evoked during PTH.
31
Zhang, Chuan-Li, Yakov Verbny, Sameh A. Malek, Peter K. Stys e Shing Yan Chiu. "Nicotinic Acetylcholine Receptors in Mouse and Rat Optic Nerves". Journal of Neurophysiology 91, n. 2 (febbraio 2004): 1025–35. http://dx.doi.org/10.1152/jn.00769.2003.
Abstract (sommario):
Receptor-mediated calcium signaling in axons of mouse and rat optic nerves was examined by selectively staining the axonal population with a calcium indicator. Nicotine (1-50 μM) induced an axonal calcium elevation that was eliminated when calcium was removed from the bath, suggesting that nicotine induces calcium influx into axons. The nicotine response was blocked by d-tubocurarine and mecamylamine but not α-bungarotoxin, indicating the presence of calcium permeable, non-α7 nicotinic acetylcholine receptor (nAChR) subtype. Agonist efficacy order for eliciting the axonal nAChR calcium response was cytisine ∼ nicotine >> acetylcholine. The nicotine-mediated calcium response was attenuated during the process of normal myelination, decreasing by approximately 10-fold from P1 (premyelinated) to P30 (myelinated). Nicotine also caused a rapid reduction in the compound action potential in neonatal optic nerves, consistent with a shunting of the membrane after opening of the nonspecific cationic nicotinic channels. Voltagegated calcium channels contributed little to the axonal calcium elevation during nAChR activation. During repetitive stimulations, the compound action potential in neonatal mouse optic nerves underwent a gradual reduction in amplitude that could be partially prevented by d-tubocurarine, suggesting an activity-dependent release of acetylcholine that activates axonal AChRs. We conclude that mammalian optic nerve axons express nAChRs and suggest that these receptors are activated in an activity-dependent fashion during optic nerve development to modulate axon excitability and biology.
32
DOMINGUES, Renan Barros, Gustavo Bruniera Peres FERNANDES, Fernando Brunale Vilela de Moura LEITE e Carlos SENNE. "Neurofilament light chain in the assessment of patients with multiple sclerosis". Arquivos de Neuro-Psiquiatria 77, n. 6 (giugno 2019): 436–41. http://dx.doi.org/10.1590/0004-282x20190060.
Abstract (sommario):
ABSTRACT Multiple sclerosis (MS) is an autoimmune, inflammatory, and degenerative disease of the central nervous system. Axonal degeneration is triggered by inflammation and is the pathological substrate of progressive disability in patients with MS. Therapeutic interventions can reduce inflammatory activity, thus delaying neurodegeneration and the progression of disability. Disease activity and neurodegeneration are assessed mainly through clinical evaluation and magnetic resonance imaging. These measures lack sensitivity and accuracy, so new biomarkers are necessary. Several markers have been studied and to date the most promising is neurofilament light (NfL), a component of the axonal cytoskeleton, which is released into cerebrospinal fluid (CSF) following axonal damage. In the present study, we review the current knowledge about CSF NfL determination in MS, clinically isolated syndrome, and radiologically isolated syndrome, and critically discuss how CSF NfL measurement may contribute to therapeutic decision-making in these patients.
33
Tonge, David, Ning Zhu, Steven Lynham, Pascal Leclere, Alison Snape, Alison Brewer, Uwe Schlomann et al. "Axonal growth towardsXenopusskinin vitrois mediated by matrix metalloproteinase activity". European Journal of Neuroscience 37, n. 4 (6 dicembre 2012): 519–31. http://dx.doi.org/10.1111/ejn.12075.
34
Cesa, Roberta, e Piergiorgio Strata. "Activity-dependent axonal and synaptic plasticity in the cerebellum". Psychoneuroendocrinology 32 (agosto 2007): S31—S35. http://dx.doi.org/10.1016/j.psyneuen.2007.04.016.
35
Lefebvre, J. L. "Increased neuromuscular activity causes axonal defects and muscular degeneration". Development 131, n. 11 (1 giugno 2004): 2605–18. http://dx.doi.org/10.1242/dev.01123.
36
Myers, Robert R., Yasufumi Sekiguchi, Shinichi Kikuchi, Brian Scott, Satya Medicherla, Andrew Protter e W. Marie Campana. "Inhibition of p38 MAP kinase activity enhances axonal regeneration". Experimental Neurology 184, n. 2 (dicembre 2003): 606–14. http://dx.doi.org/10.1016/s0014-4886(03)00297-8.
37
Galko, M. J. "Function of an Axonal Chemoattractant Modulated by Metalloprotease Activity". Science 289, n. 5483 (25 agosto 2000): 1365–67. http://dx.doi.org/10.1126/science.289.5483.1365.
38
Ratnaparkhi, Anuradha, Santanu Banerjee e Gaiti Hasan. "Altered Levels of Gq Activity Modulate Axonal Pathfinding inDrosophila". Journal of Neuroscience 22, n. 11 (1 giugno 2002): 4499–508. http://dx.doi.org/10.1523/jneurosci.22-11-04499.2002.
39
Földi, István, Krisztina Tóth, Rita Gombos, Péter Gaszler, Péter Görög, Ioannis Zygouras, Beáta Bugyi e József Mihály. "Molecular Dissection of DAAM Function during Axon Growth in Drosophila Embryonic Neurons". Cells 11, n. 9 (28 aprile 2022): 1487. http://dx.doi.org/10.3390/cells11091487.
Abstract (sommario):
Axonal growth is mediated by coordinated changes of the actin and microtubule (MT) cytoskeleton. Ample evidence suggests that members of the formin protein family are involved in the coordination of these cytoskeletal rearrangements, but the molecular mechanisms of the formin-dependent actin–microtubule crosstalk remains largely elusive. Of the six Drosophila formins, DAAM was shown to play a pivotal role during axonal growth in all stages of nervous system development, while FRL was implicated in axonal development in the adult brain. Here, we aimed to investigate the potentially redundant function of these two formins, and we attempted to clarify which molecular activities are important for axonal growth. We used a combination of genetic analyses, cellular assays and biochemical approaches to demonstrate that the actin-processing activity of DAAM is indispensable for axonal growth in every developmental condition. In addition, we identified a novel MT-binding motif within the FH2 domain of DAAM, which is required for proper growth and guidance of the mushroom body axons, while being dispensable during embryonic axon development. Together, these data suggest that DAAM is the predominant formin during axonal growth in Drosophila, and highlight the contribution of multiple formin-mediated mechanisms in cytoskeleton coordination during axonal growth.
40
Díez-Zaera, M., J. I. Díaz-Hernández, E. Hernández-Álvarez, H. Zimmermann, M. Díaz-Hernández e M. T. Miras-Portugal. "Tissue-nonspecific alkaline phosphatase promotes axonal growth of hippocampal neurons". Molecular Biology of the Cell 22, n. 7 (aprile 2011): 1014–24. http://dx.doi.org/10.1091/mbc.e10-09-0740.
Abstract (sommario):
Axonal growth is essential for establishing neuronal circuits during brain development and for regenerative processes in the adult brain. Unfortunately, the extracellular signals controlling axonal growth are poorly understood. Here we report that a reduction in extracellular ATP levels by tissue-nonspecific alkaline phosphatase (TNAP) is essential for the development of neuritic processes by cultured hippocampal neurons. Selective blockade of TNAP activity with levamisole or specific TNAP knockdown with short hairpin RNA interference inhibited the growth and branching of principal axons, whereas addition of alkaline phosphatase (ALP) promoted axonal growth. Neither activation nor inhibition of adenosine receptors affected the axonal growth, excluding the contribution of extracellular adenosine as a potential hydrolysis product of extracellular ATP to the TNAP-mediated effects. TNAP was colocalized at axonal growth cones with ionotropic ATP receptors (P2X7 receptor), whose activation inhibited axonal growth. Additional analyses suggested a close functional interrelation of TNAP and P2X7 receptors whereby TNAP prevents P2X7 receptor activation by hydrolyzing ATP in the immediate environment of the receptor. Furthermore inhibition of P2X7 receptor reduced TNAP expression, whereas addition of ALP enhanced P2X7 receptor expression. Our results demonstrate that TNAP, regulating both ligand availability and protein expression of P2X7 receptor, is essential for axonal development.
41
van den Bosch, Aletta, Nina Fransen, Matthew Mason, Annemieke Johanna Rozemuller, Charlotte Teunissen, Joost Smolders e Inge Huitinga. "Neurofilament Light Chain Levels in Multiple Sclerosis Correlate With Lesions Containing Foamy Macrophages and With Acute Axonal Damage". Neurology - Neuroimmunology Neuroinflammation 9, n. 3 (3 marzo 2022): e1154. http://dx.doi.org/10.1212/nxi.0000000000001154.
Abstract (sommario):
Background and ObjectivesTo investigate whether white matter lesion activity, acute axonal damage, and axonal density in MS associate with CSF neurofilament light chain (NfL) levels.MethodsOf 101 brain donors with MS (n = 92 progressive MS, n = 9 relapsing-remitting MS), ventricular CSF was collected, and NfL levels were measured. White matter lesions were classified as active, mixed, inactive, or remyelinated, and microglia/macrophage morphology in active and mixed lesions was classified as ramified, ameboid, or foamy. In addition, axonal density and acute axonal damage were assessed using Bielschowsky and amyloid precursor protein (APP) (immune)histochemistry.ResultsCSF NfL measurements of donors with recent (<1 year) or clinically silent stroke were excluded. CSF NfL levels correlated negatively with disease duration (p = 6.9e-3, r = 0.31). In donors without atrophy, CSF NfL levels correlated positively with the proportion of active and mixed lesions containing foamy microglia/macrophages (p = 9.85e-10 and p = 1.75e-3, respectively), but not with those containing ramified microglia. CSF NfL correlated negatively with proportions of inactive (p = 5.66e-3) and remyelinated lesions (p = 0.03). In the normal appearing pyramid tract, axonal density negatively correlated with CSF NfL levels (Bielschowsky, p = 0.02, r = −0.31), and the presence of acute axonal damage in lesions was related to higher NfL levels (APP, p = 1.17e-6). The amount of acute axonal damage was higher in active lesions with foamy microglia/macrophages and in the rim of mixed lesions with foamy microglia/macrophages when compared with active lesions containing ramified microglia/macrophages (p = 4.6e-3 and p = 0.02, respectively), the center and border of mixed lesions containing ramified microglia/macrophages (center: p = 4.6e-3, border, p = 4.6e-3, and n.s., p = 4.6e-3, respectively), the center of mixed lesions containing foamy microglia/macrophages (p = 4.6e-3 and p = 0.02, respectively), inactive lesions (p = 4.6e-3 and p = 4.6e-3, respectively), and remyelinated lesions (p = 0.03 and p = 0.04, respectively).DiscussionOur results demonstrated that active and mixed white matter MS lesions with foamy microglia show high acute axonal damage and correlate with elevated CSF NfL levels. Our data support the use of this biomarker to monitor inflammatory demyelinating lesion activity with axonal damage in MS.
42
Posse de Chaves, E., D. E. Vance, R. B. Campenot e J. E. Vance. "Alkylphosphocholines inhibit choline uptake and phosphatidylcholine biosynthesis in rat sympathetic neurons and impair axonal extension". Biochemical Journal 312, n. 2 (1 dicembre 1995): 411–17. http://dx.doi.org/10.1042/bj3120411.
Abstract (sommario):
At least 50% of the major axonal membrane lipid, phosphatidylcholine, of rat sympathetic neurons is synthesized in situ in axons [Posse de Chaves, Vance, Campenot and Vance (1995) J. Cell Biol. 128, 913-918]. In the same study we reported that, in a choline-deficient model for neuron growth, phosphatidylcholine synthesis in cell bodies is neither necessary nor sufficient for growth of distal axons. Rather, the local synthesis of phosphatidylcholine in distal axons is required for normal axon growth. We have now used three alkylphosphocholines (hexadecylphosphocholine, dodecylphosphocholine and octadecylphosphocholine) as inhibitors of PtdCho biosynthesis in a compartmented model for culture of rat sympathetic neurons. The experiments reveal that alkylphosphocholines decrease the uptake of choline into these neurons and inhibit PtdCho synthesis, but not via an effect on the activity of the enzyme CTP: phosphocholine cytidylyltransferase. We also show that when the distal axons, but not the cell bodies, are exposed to alkylphosphocholines, axonal elongation is inhibited, which is consistent with the hypothesis that phosphatidylcholine synthesis in axons, but not in cell bodies, is required for axonal elongation. The inhibitory effect of alkylphosphocholines on axon growth is most likely not mediated via a decrease in the activity of protein kinase C, since when this enzyme activity is down-regulated by treatment of the cells with phorbol ester, the alkylphosphocholines retain their ability to inhibit axonal growth.
43
Lee, Fei San, Uyen N. Nguyen, Eliza J. Munns e Rebecca A. Wachs. "Identification of compounds that cause axonal dieback without cytotoxicity in dorsal root ganglia explants and intervertebral disc cells with potential to treat pain via denervation". PLOS ONE 19, n. 5 (2 maggio 2024): e0300254. http://dx.doi.org/10.1371/journal.pone.0300254.
Abstract (sommario):
Low back pain, knee osteoarthritis, and cancer patients suffer from chronic pain. Aberrant nerve growth into intervertebral disc, knee, and tumors, are common pathologies that lead to these chronic pain conditions. Axonal dieback induced by capsaicin (Caps) denervation has been FDA-approved to treat painful neuropathies and knee osteoarthritis but with short-term efficacy and discomfort. Herein, we propose to evaluate pyridoxine (Pyr), vincristine sulfate (Vcr) and ionomycin (Imy) as axonal dieback compounds for denervation with potential to alleviate pain. Previous literature suggests Pyr, Vcr, and Imy can cause undesired axonal degeneration, but no previous work has evaluated axonal dieback and cytotoxicity on adult rat dorsal root ganglia (DRG) explants. Thus, we performed axonal dieback screening using adult rat DRG explants in vitro with Caps as a positive control and assessed cytotoxicity. Imy inhibited axonal outgrowth and slowed axonal dieback, while Pyr and Vcr at high concentrations produced significant reduction in axon length and robust axonal dieback within three days. DRGs treated with Caps, Vcr, or Imy had increased DRG cytotoxicity compared to matched controls, but overall cytotoxicity was minimal and at least 88% lower compared to lysed DRGs. Pyr did not lead to any DRG cytotoxicity. Further, neither Pyr nor Vcr triggered intervertebral disc cell death or affected cellular metabolic activity after three days of incubation in vitro. Overall, our findings suggest Pyr and Vcr are not toxic to DRGs and intervertebral disc cells, and there is potential for repurposing these compounds for axonal dieback compounds to cause local denervation and alleviate pain.
44
Benthall, Katelyn N., Ryan A. Hough e Andrew D. McClellan. "Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury". Journal of Neurophysiology 117, n. 1 (1 gennaio 2017): 215–29. http://dx.doi.org/10.1152/jn.00544.2016.
Abstract (sommario):
Following spinal cord injury (SCI) in the lamprey, there is virtually complete recovery of locomotion within a few weeks, but interestingly, axonal regeneration of reticulospinal (RS) neurons is mostly limited to short distances caudal to the injury site. To explain this situation, we hypothesize that descending propriospinal (PS) neurons relay descending drive from RS neurons to indirectly activate spinal central pattern generators (CPGs). In the present study, the contributions of PS neurons to locomotor recovery were tested in the lamprey following SCI. First, long RS neuron projections were interrupted by staggered spinal hemitransections on the right side at 10% body length (BL; normalized from the tip of the oral hood) and on the left side at 30% BL. For acute recovery conditions (≤1 wk) and before axonal regeneration, swimming muscle burst activity was relatively normal, but with some deficits in coordination. Second, lampreys received two spaced complete spinal transections, one at 10% BL and one at 30% BL, to interrupt long-axon RS neuron projections. At short recovery times (3–5 wk), RS and PS neurons will have regenerated their axons for short distances and potentially established a polysynaptic descending command pathway. At these short recovery times, swimming muscle burst activity had only minor coordination deficits. A computer model that incorporated either of the two spinal lesions could mimic many aspects of the experimental data. In conclusion, descending PS neurons are a viable mechanism for indirect activation of spinal locomotor CPGs, although there can be coordination deficits of locomotor activity. NEW & NOTEWORTHY In the lamprey following spinal lesion-mediated interruption of long axonal projections of reticulospinal (RS) neurons, sensory stimulation still elicited relatively normal locomotor muscle burst activity, but with some coordination deficits. Computer models incorporating the spinal lesions could mimic many aspects of the experimental results. Thus, after disruption of long-axon projections from RS neurons in the lamprey, descending propriospinal (PS) neurons appear to be a viable compensatory mechanism for indirect activation of spinal locomotor networks.
45
Andreasen, Mogens, e Steen Nedergaard. "Furosemide depresses the presynaptic fiber volley and modifies frequency-dependent axonal excitability in rat hippocampus". Journal of Neurophysiology 117, n. 4 (1 aprile 2017): 1512–23. http://dx.doi.org/10.1152/jn.00704.2016.
Abstract (sommario):
The loop diuretic furosemide is known to have anticonvulsant effects, believed to be exerted through blockade of glial Na+-K+-2Cl− cotransport causing altered volume regulation in brain tissue. The possibility that direct effects of furosemide on neuronal properties could also be involved is supported by previous observations, but such effects have not been thoroughly investigated. In the present study we show that furosemide has two opposing effects on stimulus-induced postsynaptic excitation in the nonepileptic rat hippocampal slice: 1) an enhancement of e-s coupling, which depended on intact GABAA transmission and was partially mimicked by selective blockade of K+-2Cl− cotransport, and 2) a decrement of field excitatory postsynaptic potentials. The balance between these effects varied, depending on the amount of synaptic drive. In addition, the compound action potential (fiber volley) recorded from the stimulated Schaffer collateral axons in stratum radiatum showed a progressive decrease during perfusion of furosemide. This effect was activity-independent, was mimicked by the stilbene derivative DIDS, and could be reproduced on fiber volleys in the alveus. Furosemide also reduced the initial enhancement of the fiber volley observed during trains of high-frequency stimulation (HFS). Results of hyperosmotic expansion of the extracellular volume, with 30 mM sucrose, indicated that both the induction and antagonism of the HFS-induced enhancement were independent of signaling via the extracellular space. Furosemide caused an increased decay of paired-pulse-induced supranormal axonal excitability, which was antagonized by ZD7288. We conclude that furosemide decreases axonal excitability and prevents HFS-induced hyperexcitability via mechanisms downstream of blockage of anion transport, which could include hyperpolarization of axonal membranes. NEW & NOTEWORTHY This study shows that the anion transporter antagonists furosemide and DIDS cause a marked decrease of axonal excitability in rat hippocampal CA1 region and prevent the induction of activity-dependent hyperexcitability in Schaffer collateral axons. The data are consistent with direct effects on axonal membrane properties. We also find that activity-dependent enhancement and depression of axonal excitability can be modified independently, suggesting that these events are governed by different underlying processes.
46
Ovsepian, Saak V., Valerie B. O’Leary, Laszlo Zaborszky, Vasilis Ntziachristos e J. Oliver Dolly. "Amyloid Plaques of Alzheimer’s Disease as Hotspots of Glutamatergic Activity". Neuroscientist 25, n. 4 (27 luglio 2018): 288–97. http://dx.doi.org/10.1177/1073858418791128.
Abstract (sommario):
Deposition of amyloid plaques in limbic and associative cortices is amongst the most recognized histopathologic hallmarks of Alzheimer’s disease. Despite decades of research, there is a lack of consensus over the impact of plaques on neuronal function, with their role in cognitive decline and memory loss undecided. Evidence has emerged suggesting complex and localized axonal pathology around amyloid plaques, with a significant fraction of swellings and dystrophies becoming enriched with putative synaptic vesicles and presynaptic proteins normally colocalized at hotspots of transmitter release. In the absence of hallmark active zone proteins and postsynaptic receptive elements, the axonal swellings surrounding amyloid plaques have been suggested as sites for ectopic release of glutamate, which under reduced clearance can lead to elevated local excitatory drive. Throughout this review, we consider the emerging data suggestive of amyloid plaques as hotspots of compulsive glutamatergic activity. Evidence for local and long-range effects of nonsynaptic glutamate is discussed in the context of circuit dysfunctions and neurodegenerative changes of Alzheimer’s disease.
47
Mariani, J., e N. Delhaye-Bochaud. "Elimination of Functional Synapses During Development of the Nervous System". Physiology 2, n. 3 (1 giugno 1987): 93–97. http://dx.doi.org/10.1152/physiologyonline.1987.2.3.93.
Abstract (sommario):
Prevailing views of how axonal projections and synapses are formed during development have changed during the last 2 decades. In many structures abundant collaterals and redundant synapses are first formed, then supernumerary axonal branches are withdrawn, and most synaptic contacts are eliminated. These phenomena involve competition between axon terminals, trophic feedback between pre- and postsynaptic partners, and modulation by factors such as functional activity.
48
Akassoglou, Katerina, Keith W. Kombrinck, Jay L. Degen e Sidney Strickland. "Tissue Plasminogen Activator–Mediated Fibrinolysis Protects against Axonal Degeneration and Demyelination after Sciatic Nerve Injury". Journal of Cell Biology 149, n. 5 (29 maggio 2000): 1157–66. http://dx.doi.org/10.1083/jcb.149.5.1157.
Abstract (sommario):
Tissue plasminogen activator (tPA) is a serine protease that converts plasminogen to plasmin and can trigger the degradation of extracellular matrix proteins. In the nervous system, under noninflammatory conditions, tPA contributes to excitotoxic neuronal death, probably through degradation of laminin. To evaluate the contribution of extracellular proteolysis in inflammatory neuronal degeneration, we performed sciatic nerve injury in mice. Proteolytic activity was increased in the nerve after injury, and this activity was primarily because of Schwann cell–produced tPA. To identify whether tPA release after nerve damage played a beneficial or deleterious role, we crushed the sciatic nerve of mice deficient for tPA. Axonal demyelination was exacerbated in the absence of tPA or plasminogen, indicating that tPA has a protective role in nerve injury, and that this protective effect is due to its proteolytic action on plasminogen. Axonal damage was correlated with increased fibrin(ogen) deposition, suggesting that this protein might play a role in neuronal injury. Consistent with this idea, the increased axonal degeneration phenotype in tPA- or plasminogen-deficient mice was ameliorated by genetic or pharmacological depletion of fibrinogen, identifying fibrin as the plasmin substrate in the nervous system under inflammatory axonal damage. This study shows that fibrin deposition exacerbates axonal injury, and that induction of an extracellular proteolytic cascade is a beneficial response of the tissue to remove fibrin. tPA/plasmin-mediated fibrinolysis may be a widespread protective mechanism in neuroinflammatory pathologies.
49
Del Negro, Ilaria, Sara Pez, Gian Luigi Gigli e Mariarosaria Valente. "Disease Activity and Progression in Multiple Sclerosis: New Evidences and Future Perspectives". Journal of Clinical Medicine 11, n. 22 (9 novembre 2022): 6643. http://dx.doi.org/10.3390/jcm11226643.
Abstract (sommario):
Multiple sclerosis (MS) is a chronic, debilitating, autoimmune-mediated, inflammatory disease of the central nervous system (CNS), in which a combination of inflammation, demyelination and axonal degeneration takes place with extreme highly interpersonal variability [...]
50
Glynn, Paul. "Axonal Degeneration and Neuropathy Target Esterase". Archives of Industrial Hygiene and Toxicology 58, n. 3 (1 settembre 2007): 355–58. http://dx.doi.org/10.2478/v10004-007-0029-z.
Abstract (sommario):
Axonal Degeneration and Neuropathy Target EsteraseThis brief review summarises recent observations which suggest a possible mechanism for organophosphate-induced delayed neuropathy (OPIDN). Neuropathy target esterase (NTE) has been shown to deacylate endoplasmic reticulum (ER) membrane phosphatidylcholine (PtdCho). Raised levels of PtdCho are present in the brains of swiss cheese/NTE mutant Drosophila together with abnormal membrane structures, axonal and dendritic degeneration and neural cell loss. Similar vacuolated pathology is found in the brains of mice with brain-specific deletion of the NTE gene and, in old age, these mice show clinical and histopathological features of neuropathy resembling those in wild-type mice chronically dosed with tri-ortho-cresylphosphate. It is suggested that OPIDN results from the loss of NTE's phospholipase activity which in turn causes ER malfunction and perturbation of axonal transport and glial-axonal interactions.