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Ultrastructural localization of SNAP-25 within the rat spinal cord and peripheral nervous system.

Synaptosomal associated protein of 25 kDa (SNAP-25) has been implicated in the membrane fusion machinery of neurotransmitter release and axonal growth. Using immunocytochemistry, we have analyzed the distribution and ultrastructural localization of SNAP-25 in selected areas of the central and peripheral nervous systems of adult rats. We show that the protein is specifically expressed in the trans face of the Golgi apparatus and in the axonal compartment. In axons and nerve endings, SNAP-25 is localized to discrete areas of the membranes of most organelles such as the axoplasmic reticulum, the axolemma, the outer membrane of mitochondria and synaptic vesicles. This wide distribution of SNAP-25 suggests that the protein is involved in the fusion of membranes in the whole axonal compartment of neurons.

Animals↗

Carbohydrate moieties of myelin-associated glycoprotein, major glycoprotein of the peripheral nervous system myelin and other myelin glycoproteins potentially involved in cell adhesion.

The myelin-associated glycoprotein (MAG) and the major glycoprotein of the peripheral nervous system myelin (P0) are two members of the family of cell adhesion molecules (CAMs). A role in cell adhesion of the carbohydrate moiety of these molecules has been attributed to the presence of N-glycans bearing the HNK-1 carbohydrate epitope. On the other hand, it has been suggested that these glycoproteins could be ligands of an endogenous mannose-binding lectin present in myelin, the cerebellar soluble lectin (CSL). In order to further document the heterogeneity of the glycans of these two CAMs, we have used several probes: an anti-carbohydrate antibody of the HNK-1 type, called Elec-39, the plant lectin concanavalin A (ConA), and the endogenous lectin CSL involved in myelin compaction. This study shows that CSL binds to a small proportion of the polypeptide chains of MAG found in adult CNS of rats and man and the polypeptide chains of P0 molecules from adult human and rat sciatic nerve. For MAG from adult rat brain, the binding of CSL is restricted to glycans of polypeptide chains which could be separated from the others according to their solubility properties. These MAG molecular entities react also with the Elec-39 antibody and with ConA. These results confirm that P0 and MAG are heterogeneous in their carbohydrate moieties.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Xenopus cadherin-6 is expressed in the central and peripheral nervous system and in neurogenic placodes.

We have cloned the cDNAs encoding the two Xenopus laevis cadherin-6 pseudoalleles (Xcad-6 and Xcad-6'), which belong to the classical type II cadherin subfamily. During embryogenesis, Xcad-6 expression starts at early neurula and increases dramatically until tadpole stages. Whole-mount in situ hybridization revealed that the transcripts are localized in the developing brain and eye. However, most prominent expression was found in the peripheral nervous system, including a major proportion of lateral line structures. Our results implicate an important contribution of cadherin-6 to the formation of placode derived nerves in Xenopus, an observation which has not been described for other species.

Amino Acid Sequence↗

Expression of complement components in the peripheral nervous system.

We have generated a SAGE (serial analysis of gene expression) library of normal sciatic nerve and found tags encoding for mRNAs of the complement system highly represented. RNA (RT-PCR and northern blot hybridization) and protein (western blot analysis and immunohistochemistry) studies confirmed these findings. High expression of classical pathway components, alternative pathway components and inhibitory components was observed in specific regions of the sciatic nerve. The first components of complement were found in axons, whereas the inhibitory components were detected in the perineurium, thereby protecting the nerve from a complement attack. Immunoreactivity towards activated complement factors was noted in post traumatic neuromas and after acute crush injury, which exemplify nerve regeneration and degeneration. We propose that local production of complement in the peripheral nervous system participates in the protection of healthy nerve and is needed for efficient clearance of myelin after injury: a prerequisite for normal regeneration and remyelination of the peripheral nerve.

Animals↗

Catastrophic secondary antiphospholipid syndrome with peripheral nervous system involvement: a case report.

A 34-year-old woman was admitted to our emergency room with a high fever, abdominal pain, dyspnea and confusion. High fever and abdominal pain had first occured after a cystocele operation 5 months earlier. Later, congestive heart failure with mural thrombus formation, peripheral polyneuropathy and ischemic cerebrovascular accident were identified in clinical follow-ups, and multiple arterial and venous thromboses were seen on cranial and abdominal magnetic resonance imaging angiography. The patient's symptoms improved with anticoagulant treatment. Antiphospholipid syndrome with elevated serum anticardiolipin IgG levels was diagnosed, and ischemic peripheral polyneuropathy with axonal degeneration was determined by sural nerve biopsy. In antiphospholipid syndrome, elevated anticardiolipin antibodies appear to be the most common acquired blood protein defect causing thrombosis. Disseminated vascular thrombosis in catastrophic antiphospholipid syndrome can result in multiorgan failure with increased morbidity and mortality. It rarely occurs secondary to various infections as in the case of our patient, who suffered postoperative intraabdominal infection. It is important to note that peripheral nervous system involvement is rare in antiphospholipid syndrome.

Acute Disease↗

Peripheral nervous system affection in experimental lipidosis induced by 4,4'-diethylaminoethoxyhexesterol.

A picture of generalized phosphoglyceride and cholesterol storage was induced, in keeping with literary data, by the experimental administration of 4,4'-diethylaminoethoxyhexesterol to rats. An asset of this model lies in the discovery that considerable storage occurs in the peripheral nervous system in contrast to the CNS, whose resistance to hexesterol is generally known. The significance of this finding is briefly discussed.

Animals↗

[Effects of methyl O-(4-hydroxy-3-methoxycinnamoly)reserpate (CD-3400) on the peripheral nervous system: especially on the smooth muscle organs].

Effects of methyl O-(4-hydroxy-3-methoxycinnamoyl) reserpate (CD-3400), a new antihypertensive agent, on the peripheral nervous system in mice, rats and guinea pigs were investigated and compared with effects of reserpine and rescinnamine. Oral administration of CD-3400 in doses from 40 to 320 mg/kg revealed a miotic action and such was weaker than that seen with reserpine and rescinnamine. The intestinal propulsion in mice was accelerated by pretreatment with reserpine, but no so with CD-3400. In isolated guinea pig vas deferens, CD-3400 at a concentration of 1 X 10(-5) M inhibited on norepinephrine-induced contraction non-competitively. However, in insolated rat vas deferens pretreated with CD-3400 (1 mg/kg, i.p.) for 5 days, norepinephrine-induced contraction was potentiated and this effect was weaker than that seen with reserpine and rescinnamine. In isolated rat vas deferens pretreated with CD-3400 for 1, 2 and 5 days,, the contraction induced by tyramine (3 X 10(-5)M) was significantly inhibited. The effect was qualitively similar to those of reserpine and rescinnamine. The intravenous administration of these three rauwolfia alkaloids in doses of 1, 2 and 4 mg/kg had no effect on the spontaneous movement of rat uterus. In isolated rat uterus pretreated with CD-3400, no significant effect was observed on oxytocin- and isoproterenol-induced responses. The peripheral actions of CD-3400 are attributed to a deterioration in the function the sympathetic nerve resulting in depletion of catecholamine stores. Efect of CD-3400 were slightly weaker than those of reserpine and rescinnamine.

Animals↗

Neurotrophin actions during the development of the peripheral nervous system.

Neurotrophins are important regulators of the development and maintenance of the vertebrate nervous system. Besides their well-established role in promoting neuronal survival during development, in vitro data suggest that they can regulate proliferation, survival, and differentiation of precursor cells. Analysis of the developing peripheral nervous system in mouse strains carrying mutations in genes encoding the neurotrophins and their receptors indicate, however, that lack of neurotrophin signalling results in specific neuronal deficits that are primarily due to neuronal death. Many of these deficits occur before final target encounter.

Animals↗

Accumulation of prion protein in the peripheral nervous system in human prion diseases.

After the finding that anti-prion antibodies stain sensory and sympathetic ganglia in variant Creutzfeldt-Jakob disease (vCJD), it was suggested that this localization supported the oral route of entry. However, prion accumulation subsequently also appeared in the peripheral nervous system (PNS) in sporadic cases. This study aims at evaluating the extent of prion protein accumulation in the PNS in all clinicopathologic subgroups of the disorder, with the exception of the familial and sporadic forms of fatal insomnia. Patients included 2 vCJD cases, 2 Gerstmann-Sträussler-Scheinker (GSS), 2 iatrogenic (iCJD), and 16 sporadic CJD (sCJD) cases. Gasserian (17) and spinal (9), celiac (2) and thoracic sympathetic (one) ganglia, spinal cord and medulla of one vCJD, 2 GSS, one iCJD, and 5 sCJD cases were examined. Immunostained sensory ganglia were seen in both vCJD, both iCJD, one GSS, and 10 sCJD cases; the celiac ganglion was positive in one of two sCJD cases, and the spinal dorsal horn and the medullary sensory nuclei were positive in one patient with vCJD, one with iCJD, and 3 with sCJD. Western blot demonstrated presence of PrP in the gasserian ganglion of one patient with sCJD. Accumulation of prion in ganglia (including autonomic) of the PNS, shared by all subgroups of spongiform encephalopathy, and in the dorsal horns and medullary sensory nuclei, shows that the sensory route is involved in the trafficking of this protein.

Adult↗

Precipitous clearance of herpes simplex virus antigens from the peripheral nervous systems of experimentally infected C57BL/10 mice.

Clearance of herpes simplex virus (HSV) from spinal ganglia of experimentally infected mice is known to be dependent on CD8+ T-cells but not on destruction of infected neurons, consistent with a non-cytolytic Tc2 response in the peripheral nervous system. Here, we demonstrate the striking rapidity of such a response in C57BL/10 mice. The number of neurons containing viral DNA and viral antigens increased until 136 h after inoculation of virulent HSV type 1 (strain SC16) into flank skin. Subsequent disappearance of HSV DNA and antigens from infected ganglia was virtually complete only 8 h later. A consistent and unexpected observation was detection of viral antigens in sensory nerve axons for at least 8 h after their disappearance from neuronal somas, raising the intriguing possibility that virus or viral proteins may be transported distally after infection has been terminated.

Animals↗

Combined axonal transport tracing and immunocytochemistry for mapping pathways of peptide-containing nerves in the peripheral nervous system.

The various combinations of axonal transport tracing and immunocytochemistry used for mapping pathways of peptide-containing nerves, and in particular those of the peripheral nervous system, are reviewed. The advantages and disadvantages of these methods are discussed. The applications and results presented illustrate the future potential value of this approach.

Animals↗

Effects of Linomide on immune cells and cytokines inhibit autoimmune pathologies of the central and peripheral nervous system.

Linomide (roquinimex, LS 2616) is a quinoline-3-carboxamide with pleiotropic immune modulating capacity and it has therapeutic effects in several experimental animal models of autoimmune diseases. Linomide has been evaluated in clinical trials for multiple sclerosis, and was indeed shown to have disease inhibitory effects. However, due to unexpected side effects recorded in patients treated with Linomide, premature termination of clinical trials was required. The basic mechanism(s) of action of Linomide in inducing beneficial effects in autoimmune diseases is still elusive. Some experimental evidence indicates that Linomide influences the regulation of the cytokine profile, resulting in the inhibition of autoimmune and inflammation pathologies. This review focuses on Linomide applied in models for autoimmune and inflammation pathologies of the central and the peripheral nervous system, and summarises its very encouraging disease inhibitory effects and their potential pharmacological basis. The beneficial effects recorded with Linomide in both experimental and clinical trials emphasise the possible value of substances with Linomide-like activity for clinical use in autoimmune and inflammation pathologies in the near future.

Adjuvants, Immunologic↗

The re-innervation of olfactory glomeruli following transection of primary olfactory axons in the central or peripheral nervous system.

The re-innervation of the olfactory bulb has been studied in rats in which the primary afferent axons were transected either in the peripheral nervous system, on the intracranial side of the cribriform plate, or in the central nervous system, in the nerve fibre layer of the bulb. Both procedures resulted in denervation of glomeruli on the dorsal surface of the olfactory bulb. Re-innervation of these glomeruli was first seen approximately three weeks after operation and was largely completed by the sixth week, irrespective of the site of the lesion. The similarity of the timing of re-innervation following the two procedures indicates that the cut fibres did not regenerate from their sites of transection. It is much more probable that the re-innervation axons were those of neurons newly generated in the olfactory epithelium. This view is supported by the results of other investigations, in which retrograde degeneration and subsequent replacement of the neurons have been found to follow transection of the olfactory nerves. After transection of the olfactory nerves, the new axons entering the bulb grew through the site of the lesion, across the interface between peripheral and central nervous tissue, through the nerve fibre layer and into the glomeruli. Thus, they followed the same course as normally growing primary olfactory axons. After the afferent fibres had been cut within the olfactory bulb, the site of transection was transformed into a scar composed largely of astrocytes. No olfactory axons grew through the scar and none passed beneath it in the deeper layers of the bulb. However, by tracing the anterograde axonal transport of horseradish peroxidase, it has been shown that axons immediately rostral to the lesion terminated in the re-innervated glomeruli. These denervated glomeruli were, therefore, probably re-innervated by axons that grew through the intact central nervous tissue of the nerve fibre layer on either side of the lesion.

Animals↗

CHox11L2, a Hox11 related gene, is expressed in the peripheral nervous system and subpopulation of the spinal cord during chick development.

cHox11L2, the chick counterpart of mouse Hox11L2, was isolated. cHox11L2 was expressed in the developing chick peripheral nervous system, i.e. sensory cranial nerves of placodal ectoderm origin, sympathetic ganglia, dorsal root ganglia and enteric ganglia as well as a limited regions of the spinal cord. In neuronal derivatives of the neural crest, cHox11L2 was expressed in the postmigratory cells and not in the migrating neural crest cells. Furthermore, intense signals of cHox11L2 mRNA were detected also in the spinal cord and the dorsal roots of 10-day embryos. No transcripts were detected in the spinal cord of the postnatal day-2 animals. These results suggest that cHox11L2 might play a role in neuronal differentiation during chick nervous system development.

Amino Acid Sequence↗