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PubMed2000

Facial motor neuron regeneration induces a unique spatial and temporal pattern of myristoylated alanine-rich C kinase substrate expression.

We have previously shown that the myristoylated alanine-rich C kinase substrate, a primary protein kinase C substrate in brain that binds and cross-links filamentous actin, is enriched in neuronal growth cones and is developmentally regulated in brain. Here we examined myristoylated alanine-rich C kinase substrate expression in the facial motor nucleus during axonal regeneration following facial nerve axotomy or facial nerve resection lesions, which impede regeneration, or following motor neuron degeneration induced by the retrograde neurotoxin ricin. For comparative purposes, the protein kinase C substrates myristoylated alanine-rich C kinase substrate-like protein and growth-associated protein-43 were examined in parallel. Myristoylated alanine-rich C kinase substrate messenger RNA exhibited a robust increase in both neurons and non-neuronal cells in the facial motor nucleus beginning four days after axotomy, peaked at seven days (2.5-fold), and declined back to baseline levels by 40 days. Myristoylated alanine-rich C kinase substrate protein similarly exhibited a twofold elevation in the facial motor nucleus determined four and 14 days post-axotomy. Following nerve resection, myristoylated alanine-rich C kinase substrate messenger RNA levels increased at seven days and returned to baseline levels by 40 days. Unlike myristoylated alanine-rich C kinase substrate messenger RNA, myristoylated alanine-rich C kinase substrate-like messenger RNA levels did not increase in the facial motor nucleus at any time point following nerve axotomy or resection, whereas growth-associated protein-43 messenger RNA exhibited a rapid (one day) and prolonged (40 days) elevation in facial motor nucleus neurons following either nerve axotomy or resection. Ricin-induced degeneration of facial motor neurons elevated myristoylated alanine-rich C kinase substrate and myristoylated alanine-rich C kinase substrate-like messenger RNAs in both microglia (lectin-positive) and astrocytes (glial fibrillary acidic protein-positive).Collectively, these data demonstrate that myristoylated alanine-rich C kinase substrate exhibits a unique expression profile in the facial motor nucleus following facial nerve lesions, and it is proposed that myristoylated alanine-rich C kinase substrate may serve to mediate actin-membrane cytoskeletal plasticity in both neurons and glial cells in response to protein kinaseC-mediated signaling during nerve regeneration and degeneration.

Animals↗
PubMed2000

Up-regulation of growth-associated protein 43 mRNA in rat medial septum neurons axotomized by fimbria-fornix transection.

Transection of septohippocampal fibres is widely used to study the response of CNS neurons to axotomy. Septohippocampal projection neurons survive axotomy and selectively up-regulate the transcription factor c-Jun. In the present study we investigated whether these cells concomitantly up-regulate the growth-associated protein-43 (GAP-43), a potential target gene of c-Jun implicated in axonal growth and regeneration. Using in situ hybridization histochemistry (ISHH) it was demonstrated that postlesional c-jun mRNA expression is accompanied by an increased expression of GAP-43 mRNA in the medial septum 3 days following fimbria-fornix transection (FFT). The increase reached a maximum at 7 days and gradually declined thereafter (17 days, 3 weeks). Retrograde prelabeling with Fluoro-Gold followed by axotomy and ISHH revealed that GAP-43 mRNA was up-regulated in septohippocampal projection neurons. Colocalization of GAP-43 mRNA and choline acetyltransferase protein showed that GAP-43 mRNA was expressed by cholinergic medial septal neurons after axotomy. Selective immunolesioning of the cholinergic component of the septohippocampal projection with 192 IgG-saporin followed by FFT demonstrated that GAP-43 mRNA was also synthesized by axotomized GABAergic neurons. These results demonstrate an up-regulation of GAP-43 mRNA in axotomized septohippocampal projection neurons independent of their transmitter phenotype which is closely correlated with c-Jun expression. Because the GAP-43 gene contains an AP-1 site, we hypothesize a c-Jun-driven up-regulation of GAP-43 in lesioned medial septal neurons that may contribute to their survival and regenerative potential following axotomy.

Animals↗
PubMed2002

Expression of gp130 and leukaemia inhibitory factor receptor subunits in adult rat sensory neurones: regulation by nerve injury.

Members of the interleukin-6 (IL-6) family of cytokines have been implicated as major mediators of the response of the adult nervous system to injury. The basis for an interaction of IL-6 cytokines with adult sensory neurones has been established by analysing the levels and distribution of the two signal-transducing receptor subunits, glycoprotein 130 (gp130) and leukaemia inhibitory factor receptor (LIFR), in the dorsal root ganglion (DRG) of male adult rats before and following nerve injury. All sensory neurones express gp130-immunoreactivity (IR) in the cytoplasm and on the plasma membrane. Levels of gp130 and its intracellular distribution remained unchanged up to 14 days following sciatic nerve axotomy. LIFR-IR was largely absent from the cytoplasm and plasma membrane of sensory neurones, but confined almost exclusively to the nuclear compartment. However, following axotomy, punctate cytoplasmic LIFR-IR was detected which persisted up to 28 days following axotomy. The expression of cytoplasmic LIFR 2 days post-axotomy was proportionally greater in a subset of small diameter sensory neurones which expressed either the sensory neuropeptide CGRP or the cell surface marker isolectin B4. The coexpression of gp130 and LIFR in the same intracellular compartment following axotomy conveys potential responsiveness of injured sensory neurones to members of the IL-6 family of cytokines.

Animals↗
PubMed2003

Growth associated protein-43 mRNA expression in nucleus ambiguus motoneurons after recurrent laryngeal nerve injury in the rat.

OBJECTIVE: To investigate the time-dependent differences in growth associated protein-43 (GAP-43) mRNA expression in the nucleus ambiguus (NA) motoneurons after recurrent laryngeal nerve (RLN) transection in the rat. MATERIAL AND METHODS: Animals were sacrificed on Days 1, 7, 14 and 21 after axotomy. The sections were then processed for in situ hybridization of GAP-43 mRNA. RESULTS: GAP-43 mRNA transiently increased after axotomy, reaching a peak on postoperative Day 7, and then decreased gradually at 14 and 21 days after axotomy. The peak period of GAP-43 expression in the NA is different from those in the facial and hypoglossal nuclei after axotomy. CONCLUSION: We have already reported that neuronal nitric oxide synthase (nNOS) is induced in the NA motoneurons after axotomy and reaches a peak on postoperative Day 14. This study shows that the expressions of GAP-43 and nNOS are chronologically different.

Animals↗
PubMed2000

Effects of neurotrophic factors on motoneuron survival following axonal injury in newborn rats.

Using two different lesion models, the spinal root avulsion and the distal nerve axotomy, the present study investigated effects of known neurotrophic factors on motoneuron survival in newborn rats. Results of the present study show that 100% of motoneurons in the lesioned spinal segment die at 1 week following root avulsion, and more than 80% of them die at 2 weeks following distal nerve axotomy. Local application of GDNF can rescue 92% of motoneurons up to 1 week from degeneration due to root avulsion and almost 100% of them up to 2 weeks from degeneration due to distal nerve axotomy. Local application of BDNF fails to prevent any motoneuron death in newborn rats following root avulsion, but it can rescue about 50% of motoneurons up to 2 weeks from degeneration due to distal nerve axotomy. CNTF and IGF-1 fail to prevent any motoneuron death following either distal nerve axotomy or root avulsion. Thus, comparing all the neurotrophic factors tested in this study, GDNF is most effective in preventing death of motoneurons following axonal injury in newborn rats.

Animals↗
PubMed2005

Quantification of N-CAM and N-cadherin expression in axotomized and crushed rat sciatic nerve.

Adhesion molecules are important in supporting axonal regeneration. Qualitative studies have described increased expression of neural cell adhesion molecule (NCAM) and N-cadherin in models of nerve injury allowing active regeneration. In this study we have used quantitative immunohistochemistry to compare expression of NCAM and N-cadherin after nerve injury either with active regeneration (crush) into the distal stump or without (axotomy and capping). Quantification was performed 15 days after axotomy in proximal and distal stumps. Quantification after crush either proximal, distal or within the crushed area was performed at 2, 7, 15 and 30 days after injury. Axotomy induced increases in expression in proximal stumps between two and three times those in uninjured nerves for both molecules. In distal stumps, N-cadherin levels increased seven-fold, yet NCAM levels did not exceed control values. After crush, NCAM immunoreactivity increased in the crushed area and distal stump in contrast to axotomy and NCAM-positive axons co-localized with PGP9.5. N-cadherin levels in the distal stump increased above control levels, but the magnitude of the increase seen after crush was different to those seen after axotomy. In conclusion, increased expression of adhesion molecules, particularly NCAM, in the distal stump of injured nerves is dependent upon the presence of regenerating axons.

Animals↗
PubMed1993

Altered gene expression after optic nerve transection: reduced neurofilament expression as a general response to axonal injury.

Previous studies have shown that axonal injury (axotomy) in neurons of the mammalian peripheral nervous system (PNS) results in a recapitulation of the developmental program for cytoskeletal gene expression; these changes include the increased expression of a developmentally regulated isotype of beta-tubulin (class II) and reduced neurofilament (NF) expression. In the present study we examined the abundance of mRNAs encoding the low-molecular-weight NF protein (NF-L) and class II beta-tubulin in RNA purified from the retinae of newborn rats, from the retinae of adult rats at 2, 7, and 14 days after intracranial transection of the ipsilateral optic nerve, and from contralateral control retinae. In order to facilitate comparison with representative PNS neurons, parallel analyses were carried out in axotomized dorsal root ganglion (DRG) sensory neurons. Since NF-L and class II beta-tubulin are neuron-specific proteins, axotomy-induced alterations in the levels of retinal mRNAs encoding these proteins largely reflect corresponding changes in expression by retinal ganglion cell neurons. Comparison of retinal RNA from newborn and adult (70-day-old) animals demonstrated a postnatal increase in NF-L and a decline in class II beta-tubulin mRNAs comparable to those previously described in DRG neurons. Reductions in NF-L mRNA levels were noted in retina at 2, 7, and 14 days after axotomy and in DRG neurons at 7 and 14 days after axotomy. The abundance of class II beta-tubulin mRNAs increased after axotomy in DRG neurons, but not in retina.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

A time-dependent loss of retrograde transport ability in distally axotomized rubrospinal neurons.

Studies on the effect of axotomy on adult intrinsic central projection neurons have generally assumed that the severed proximal axonal stumps were still capable of retrogradely transporting tracer at varying times after injury. Failure of transport was interpreted as neuronal death, which is at odds with current understanding that central projection neurons survived distal axotomy. We used lumbar spinal cord-projecting rubrospinal neurons of the rat as a model to evaluate the ability of injured neurons to transport tracer retrogradely at different times after distal axotomy. We examined only the caudal part of the red nucleus, since rubrospinal neurons are concentrated here. In control animals, tracer applied to the rubrospinal tract at the T10 vertebral level labeled ventrolateral rubral neurons, while C3 application marked all rubral neurons. From 3 days after a T10 axotomy and tracer application, most ventrolateral neurons were no longer labeled by another tracer application at the C3 vertebral level via an axonal cut. The phenomenon was not caused by tracer toxicity, since a T10 tractotomy without tracer application also prevented these axotomized neurons from being labeled when treated similarly. Thus, neuronal retrograde transport capability was seriously retarded 3 days after a distal axotomy. Loss of retrograde transport may merely suggest that a mechanism no longer in service has been switched off, or perhaps it may insulate injured neurons from the effect of lesion site-derived factors. Using this property, we were able to localize cervical spinal cord-projecting rubrospinal neurons in the caudal red nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of peripheral nerve cut on neuropeptides in dorsal root ganglia and the spinal cord of monkey with special reference to galanin.

Using the indirect immunofluorescence method and in situ hybridization, the localization and levels of immunoreactivities and mRNAs for several neuropeptides were studied in lumbar dorsal root ganglia and spinal cord of untreated monkeys (Macaca mulatta) and after unilateral transection of the sciatic nerve. Immunoreactive galanin, calcitonin gene-related peptide, substance P and somatostatin and their mRNAs were found in cell bodies in dorsal root ganglia of untreated monkeys and on the contralateral side of the monkeys with unilateral sciatic nerve lesion. After axotomy there was a marked decrease in the number of calcitonin gene-related peptide-, substance P- and somatostatin-positive neurons in dorsal root ganglia ipsilateral to the lesion, whereas the number of galanin positive cells strongly increased. A few neuropeptide tyrosine-positive cells were seen in after axotomy, whereas no such neurons were found in controls. No vasoactive intestinal polypeptide-, peptide histidine isoleucine-, cholecystokinin-, dynorphin-, enkephalin-, neurotensin- or thyrotrophin releasing hormone-positive cell bodies were seen in dorsal root ganglia of any of the groups studied. In the dorsal horn of the spinal cord all peptide immunoreactivities described above, except thyrotropin releasing hormone, were found in varying numbers of nerve fibres with a similar distribution in untreated monkeys and in the contralateral dorsal horn in monkey with unilateral sciatic nerve lesion. Two cholecystokinin antisera were used directed against the C- and N-terminal portions, respectively, showing a distinctly different distribution pattern in the dorsal horn. Somatostatin- and dynorphin-like immunoreactivities were also observed in small neurons in the dorsal horn. No certain effect of axotomy on these interneurons could be seen. However, marked changes were observed after this type of lesion for some peptide containing fibres in the ipsilateral dorsal horn. Thus, there was a marked increase in galanin-like immunoreactivity, whereas calcitonin gene-related peptide-, substance P-, somatostatin-, peptide histidine isoleucine neurotensin- and cholecystokinin-like immunoreactivities decreased. No changes could be observed in neuropeptide tyrosine or enkephalin-positive fibres. The present results demonstrate marked ganglionic and transganglionic changes in peptide levels after peripheral axotomy. When compared to published results on the effect of axotomy on peptides in dorsal root ganglia and spinal cord of rat, both similarities and differences were encountered.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Control of neuron shape during development and regeneration.

We have examined the ability of Mueller reticulospinal neurons in the CNS of the larval sea lamprey to sprout following axonal and dendritic injury. Axotomy induces regenerative sprouting exclusively from the axon stump if it occurs at a site distant from the soma in the spinal cord. However, axotomy within the hindbrain at a site close to the soma results in profuse neuritic sprouting from the dendrites. The gross morphology and trajectories of these "dendritic" sprouts resemble those of regenerating axons. Amputation of Mueller cell dendrites (dendrotomy) without axotomy does not result in neuritic sprouting from either the axon or dendrites, indicating that axotomy is specifically required for sprouting to occur. However, dendrotomy is capable of altering the distribution of sprouting in a previously axotomized Mueller cell by inducing sprouting at the site of the dendrotomy lesion. Sprouts of both dendritic and axonal origin tend to follow linear, rostrocaudally oriented paths along or near the ventral surface of the hindbrain. Some sprouts form very large, palmate growth cones on the marginal surface, which in turn give rise to many branches that continue to grow either rostrally or caudally along the surface of the brain. We discuss the possibility that both dendritic and axonal sprouts evoked by axotomy of Mueller neurons are recapitulating initial axonal development during embryogenesis, and that their trajectories are determined by developmental guidance cues persisting in the ventral hindbrain.

Animals↗
PubMed1974

The effect of injury on two hydrolases in the hypoglossal nucleus, with quantitative data on N-acetyl-beta-glucosaminidase.

N-acetyl-beta-glucosaminidase and acid phosphatase were studied histochemically in sections of hypoglossal nuclei of normal adult male albino rats, and rats from 1 to 56 days after axotomy of the left hypoglossal nerve, or after injection of botulinum toxin into the left side of the tongue. Both axotomy and botulinum caused a diminution of neurone perikaryal glucosaminidase reaction product on the operated side, but an increase of reaction product elsewhere in the operated nucleus. Whereas the effect of axotomy lasted from 5 to 42 days post-operatively, that of botulinum ceased between 28 and 42 days. Axotomy and botulinum both caused an increase of neuronal acid phosphatase (after a short incubation time) from 2 to 21 days post-operatively in injured nuclei. Glucosaminidase reaction product measured microdensitometrically in isolated cells showed a statistically significant diminution in injured neurones at 18 days after axotomy. There was no change in the amount of reaction product per cell in pericytes, astrocytes, or non-astrocyte glia. Sections scanned quantitatively showed that normal and operated nuclei had a similar amount of reaction product, thus the neuronal diminution must be balanced by the increase elsewhere, either in the elevated numbers of non-astrocyte glia, or in the neuropil.

Acetylglucosaminidase↗
PubMed1979

Pharmacological analysis of the functional ontogeny of the nigrostriatal dopaminergic neurons.

Functional development of the dopaminergic nigrostriatal projection was studied by determining the age at which the biochemical responses of these neurons to physical or pharmacological manipulation are similar to those of adult neurons. Transection of the pathway acutely elevates striatal dopamine in adult and 8- and 10-day-old rats, but not in the 4- or 6-day-old animal. This axotomy-induced increase in striatal dopamine is believed to be a response of the dopaminergic terminals to cessation of impulse traffic and is secondary to a decrease in dopamine release and a concomitant increase in dopamine synthesis resulting from tyrosine hydroxylase activation. Therefore, this response to axotomy acts as an indicator of (1) the presence of impulse traffic in the pathway, and (2) the ability of tyrosine hydroxylase to be activated in response to a reduction in such impulse traffic. In vivo estimation of tyrosine hydroxylase activity showed that axotomy activates the enzyme at 10 days, but not at 4 days, whereas gamma-hydroxybutyrate is effective at both ages. The fact that the enzyme can be activated by gamma-hydroxybutyrate at 4 days indicates that the lack of effect of axotomy at this age is due to the absence of impulse traffic in the system. This conclusion is supported by the finding that the AMT-induced depletion of striatal dopamine is not related to impulse conduction at 4 days since transection of the pathway has no effect on the rate of dopamine loss whereas such transection blocks the AMT-induced depletion at 10 days of age. Nevertheless, despite the absence of neuronal activity at 4 days of age, these neurons are capable of generating and conducting impulse traffic since both 4- and 10-day-old rats showed increased striatal dihydroxyphenylacetic acid (DOPAC) levels when treated with haloperidol indicating increased dopamine release; such increase in DOPAC being dependent on an intact pathway. Given this data, the most parsimonious explanation of the abrupt development of the response to axotomy after the 6th day of age is that an event occurs which physiologically initiates impulse traffic. This event may be activation of afferent neuronal inputs to the cell bodies of the nigrostriatal projection.

Aging↗
PubMed1990

Role of activity in the selection of new electrical synapses between adult Helisoma neurons.

Our aim was to determine whether neural activity in the form of sodium-dependent action potentials play a role in the formation, maintenance and specificity of electrical synapses between regenerating neurons. We axotomized buccal neurons of the mollusc, Helisoma trivolvis, and placed ganglia into organ culture in the absence or presence of tetrodotoxin (TTX), a specific sodium channel blocker. Electrical coupling was measured using intracellular microelectrodes positioned within the soma of identified neurons. Neurite outgrowth was assessed by epifluorescence microscopy after filling neurons by iontophoresis with Lucifer yellow. Previous studies found that two days after axotomy transient electrical synapses form between heterologous neurons (e.g. buccal neurons 4 and 5). Five days after axotomy these transient connections disappeared and a new electrical synapse was stabilized between the paired buccal neurons 5. To determine whether blocking neural activity with TTX affected the specificity and formation of new electrical synapses, we examined electrical coupling between the heterologous neurons 4 and 5 two days after axotomy, and the paired buccal neurons 5 five days after axotomy. Our electrophysiological recordings indicated that different neurons in the buccal ganglion varied in their sensitivity to TTX (i.e. sensitivity of buccal neurons 19 greater than 5 greater than 4), but spontaneous activity was abolished in all 3 neurons by 2 x 10(-5) M TTX. Furthermore, the inhibitory effects of TTX occurred within seconds of superfusion and persisted for at least 6 days. Inhibition of activity by TTX could be reversed after superfusion with normal saline. Neurite outgrowth from axotomized neurons was not appreciably altered in the presence of TTX. Furthermore, no differences in the incidence of electrical coupling or the coupling resistance were detected between neurons 4 and 5 two days after axotomy and organ culture in the presence of TTX. However, electrical coupling between the symmetrically paired neurons 5 was elevated in the presence of TTX after 5 days. We conclude from these results that neural activity in the form of sodium-dependent action potentials does not play an important role in the formation or breaking of transient electrical synapses during neuronal regeneration in the mollusc Helisoma trivolvis.

Action Potentials↗
PubMed1993

Regulation of aberrant neurofilament phosphorylation in neuronal perikarya. IV. Evidence for the involvement of two signals.

Axonal regeneration over long distances is dependent upon events occurring both in the distal stump and in the neuronal cell body. Little is known concerning how events in the distal stump influence the cell body response to injury, or the axon reaction. In the present study, we examined this relationship for one component of the axon reaction (i.e. aberrant neurofilament (NF) phosphorylation) in the C57BL/Ola (Ola) mouse mutant, a model which exhibits delayed Wallerian degeneration (up to 3 weeks) and retarded regeneration of sensory neurons. Non-axotomized normal (C57/6J/BL) and Ola mice demonstrated modest immunostaining to phosphorylated NF (pNF) epitopes (using monoclonal antibody 06-17) in some (11%) L4 dorsal root ganglion (DRG) neuronal cell bodies. In normal mice, modest to intense immunoreactivity was present in 43% of DRG neurons at 1 week following a sciatic nerve crush (axotomy). The intensity and extent of staining declined with reinnervation, being reduced slightly at 2 weeks and more notably by 3 weeks following axotomy. In Ola mice, the intensity and extent (43%) of staining were not different from normal axotomized mice at 1 week following axotomy. However, the intensity was less and the extent of staining reduced by 28% at 2 weeks following axotomy. By 3 weeks, staining levels were again increased, being similar to that observed in Ola and normal mice at 1 week following axotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Differential regulation of c-JUN expression in rat retinal ganglion cells after proximal and distal optic nerve transection.

In adult rats, the distance between the site of axotomy and the cell body influences the ability of retinal ganglion cells (RGCs) to survive and regenerate an axon. Optic nerves of adult rats were transected 2 mm or 6 mm from the optic bulb and RGCs labeled with the fluorescent marker fluorogold. The time course of c-JUN expression was monitored immunocytochemically between 3 days and 4 weeks after axotomy. c-JUN expression began later and declined faster after distal axotomy than after proximal transection of the optic nerve. However, at the same time significantly more RGCs survived after distal than after proximal axotomy 3 and 4 weeks after axotomy. These findings suggest that survival and expression of c-JUN in rat RGCs are independently regulated by the length of the optic nerve stump after lesion.

Animals↗
PubMed1995

Effects of postganglionic nerve section on synaptic transmission in the superior cervical ganglion of the guinea-pig.

In sympathetic neurons, axotomy induces a marked depression in synaptic transmission. We asked whether the decrease in synaptic efficacy observed in a given axotomized cell is more severe if most of the postsynaptic neurons are also injured. Accordingly, we studied if the synaptic depression induced by axotomy in neurons with axons running in a postganglionic nerve is influenced by section of other postganglionic nerves. The excitatory postsynaptic potentials evoked by preganglionic stimulation were recorded intracellularly in an in vitro preparation of the superior cervical ganglion. Eight days after cutting the inferior postganglionic nerve, postsynaptic potentials recorded from neurons projecting through this nerve were smaller (median = 6 mV, n = 62) than the controls (median = 34 mV, n = 89), but were similar to those found after sectioning the inferior nerve plus most postganglionic nerves (median = 5 mV, n = 70). If the inferior nerve was left intact, but most postganglionic branches were cut, the synaptic potentials recorded from inferior nerve neurons were normal (median = 33 mV, n = 77). It is concluded that the synaptic depression induced by axotomy in a sympathetic neuron is not affected by axotomy of nearby ganglion cells, even if they share part of their presynaptic axons. This suggests that the effect of axotomy is restricted to the synaptic terminals on the injured neuron.

Animals↗
PubMed1997

Islet amyloid polypeptide and calcitonin gene-related peptide expression are down-regulated in dorsal root ganglia upon sciatic nerve transection.

Islet amyloid polypeptide (IAPP) is structurally related to calcitonin gene-related peptide (CGRP) and has been implicated in glucose homeostasis and diabetes pathogenesis because it is expressed in insulin cells and forms amyloid in pancreatic islets from type II diabetic patients. IAPP is also constitutively co-expressed with CGRP in rat sensory neurons. Whether expression of IAPP is altered by nerve injury with or without regeneration was investigated in adult rats subjected to unilateral sciatic axotomy; IAPP and CGRP expression were determined by quantitative in situ hybridization and immunocytochemistry at days 3, 10 and 30 after axotomy. In ipsilateral L4-L5 dorsal root ganglia (DRG), the percentages of nerve cell profiles labelled for IAPP and CGRP mRNA were reduced at all time points studied. IAPP and CGRP mRNA expression were lower in nerve cell profiles in ipsilateral DRGs compared to the contralateral side after axotomy alone whereas epineurial nerve suture maintained or restored IAPP and CGRP expression. The numbers of IAPP- and CGRP-immunoreactive DRG nerve cell profiles and dorsal horn fibers were reduced on the ipsilateral side at all time points. Thus, IAPP and CGRP expression are down-regulated upon axotomy. Nerve repair maintains or restores IAPP and CGRP expression in individual neurons but does not prevent the loss of CGRP/IAPP phenotype of some of these neurons in response to axotomy.

Amyloid↗
PubMed1997

Persisting expression of galanin in axotomized mamillary and septal neurons of adult rats labeled for c-Jun and NADPH-diaphorase.

In adult male rats, the expression of the neuropeptide galanin and its co-localization with the c-Jun transcription factor and the NADPH-diaphorase, the marker enzyme for the nitric oxide synthase (NOS), was investigated by immunohistochemistry in axotomized neurons following unilateral stereotaxic transection of the (a) mamillo-thalamic tract, (b) medial forebrain bundle, (c) fimbria fornix bundle and (d) sciatic nerve. This surgical procedure resulted in axotomy of neurons of (a) mamillary ncl. (MnM), (b) substantia nigra compacta (SNC) and paraventricular ncl. of thalamic (PF) neurons, (c) medial septum (MS) and vertical diagonal band of Broca (VDB), and (d) sciatic motoneurons and dorsal root ganglia (DRG). In all of these axotomized neuronal subpopulations, expression of c-Jun appeared between 24 and 36 h post-axotomy and persisted on substantial levels for 15 days in the SNC and for 30-50 days in the MnM, PF, MS, VBD, sciatic DRG and motoneurons. Expression of galanin was seen in axotomized MnM, MS and DRG, but not in SNC, PF and sciatic motoneurons. Galanin-immunoreactivity (IR) appeared between 3 and 5 days after nerve fiber transection and persisted up to 50 days in the MnM, MS and DRGs. The cytoplasmic galanin-IR was almost completely restricted to those neurons showing a nuclear c-Jun expression. Moreover, galanin expression showed a long-lasting co-localization with those neurons that exhibited an increased NADPH-diaphorase reactivity in the MnM and DRG or a residual NADPH-diaphorase reactivity in MS post-axotomy. Very similar to galanin, NADPH-diaphorase was not affected by axotomy in the SNC, PF or sciatic motoneurons. Our findings suggest a common mechanism for galanin and NOS (NADPH-diaphorase activity) expression. Since the galanin promotor contains an AP-1 binding site, c-Jun might trigger the lasting induction of galanin in NOS-positive central neurons that survive the axotomy-evoked injury.

Animals↗