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The existence of a new protein, Y, (M.W.: 57,000; pI: 5.5) was revealed in different neuronal cells from the peripheral nervous system by two-dimensional gel analysis, peptide mapping and immunological detection.
We have produced a monoclonal antibody (PM43) selectively reactive with formalin-fixed paraffin-embedded peripheral nervous system (PNS) myelin. The hybridomas were generated by fusion of mouse myeloma cell line Sp2/0 with spleen cells of BALB/c mice immunized with cultured human melanocytes. Hybridomas were screened by the indirect immunoperoxidase assay. Ouchterlony analysis showed the immunoclass of PM43 to be IgM. By the immunoaffinity chromatography technique, among others a 43-kDa protein was isolated from PNS myelin. The antigenic determinant of PM43 in the mouse is expressed with a similar tissue distribution as observed in man. Expression of the antigenic determinant does not become visible until after birth in mice. PM43 opens further possibilities for the use of anti-myelin antibodies in the study of myelination and demyelination processes in the PNS and remyelination processes in the central nervous system.
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Preganglionic brachial plexus injuries fall into two categories according to the lesion site, root avulsion injury and root rupture injury. The latter type of injury involves part of the peripheral nervous system (PNS) component at the injured spinal cord surface. Previous investigators have used rhizotomy of experimental animals as a model for dorsal root rupture injury. However, the effect on the central nervous system (CNS)-PNS junction accompanied by the mechanical stress from traction force is hard to estimate in this model. The current study aimed to demonstrate temporal molecular alterations from the CNS-PNS junction to the ruptured dorsal root after traction injury by immunohistochemical procedures. At 28 days after dorsal rupture injury, GFAP-positive structures could be clearly identified showing rather straight lines from the centro-peripheral junction toward the peripheral stump in the ruptured dorsal root. Immunoelectron microscopy for GFAP verified GFAP IR within the astrocytic processes at the injured dorsal root at 28 days after dorsal rupture injury. Glial cell line-derived neurotrophic factor immunoreactivity (GDNF IR) was slightly upregulated within the Schwann cell bodies on the injured dorsal root at 24-48 h after rupture injury. However, GDNF IR had appeared showing a process-like profile on the ruptured dorsal root by 28 days, and it was closely related with GFAP-positive structures. In contrast, a small increase in GFAP IR was only detected on the proximal side on the rhizotomized dorsal root at 28 days after rhizotomy. A marked decrease in NF IR and S-100 IR was observed at the ruptured dorsal root from 7 days. On the other hand, laminin IR was strongly upregulated on the ruptured dorsal root from 48 h to 7 days, and was still evident at 28 days. We therefore conclude that the astrocytes show a unique ability to extend their processes toward the stump. This ability may provide a new medium for the study of axonal regeneration in future clinical experiments.
The authors present a case of malignant lymphoma in a man aged 64 years. Neoplastic infiltrations mainly in the form of perivascular accumulations were limited to the central nervous system (both central and peripheral). In the histological examinations of internal organs including lymph nodes and spleen no neoplastic tissue was found.
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We report a case of acute endocarditis with the unusual presentation of mononeuritis multiplex at onset. Mononeuropathy was the only detected neurological sign. The presence of muscular abscesses compressing the peripheral nervous system could lie at the basis of the pathophysiological mechanism responsible for acute mononeuropathy.
The histochemical distribution of some aminotransferases at various levels through the midbrain and cerebrum and in the peripheral nervous system of the rat has been described. The selective localization of the reaction product in the neurons and the neuropil was the same for the aminotransferases studied. There was a difference in the intensity of the enzyme activity. The white matter was negative, and only the glial cells and the blood vessels exhibit transaminase activity. Some nuclei showed an intensive reaction in the neurons and neuropil: nuel. ruber, substantia nigra, hypothalamic nuclei, Ammon's horn. A high activity was observed in the ganglion cell, and the nerve fibres were negative. There was a great similarity between the pattern of distribution for aminotransferases and that for some dehydrogenases.
Myelination allows the fast propagation of action potentials at a low energetic cost. It provides an insulating myelin sheath regularly interrupted at nodes of Ranvier where voltage-gated Na+ channels are concentrated. In the peripheral nervous system, the normal function of myelinated fibers requires the formation of highly differentiated and organized contacts between the myelinating Schwann cells, the axons and the extracellular matrix. Some of the major molecular complexes that underlie these contacts have been identified. Compact myelin which forms the bulk of the myelin sheath results from the fusion of the Schwann cell membranes through the proteins P0, PMP22 and MBP. The basal lamina of myelinating Schwann cells contains laminin-2 which associates with the glial complex dystroglycan/DPR2/L-periaxin. Non compact myelin, found in paranodal loops, periaxonal and abaxonal regions, and Schmidt-Lanterman incisures, presents reflexive adherens junctions, tight junctions and gap junctions, which contain cadherins, claudins and connexins, respectively. Axo-glial contacts determine the formation of distinct domains on the axon, the node, the paranode, and the juxtaparanode. At the paranodes, the glial membrane is tightly attached to the axolemma by septate-like junctions. Paranodal and juxtaparanodal axoglial complexes comprise an axonal transmembrane protein of the NCP family associated in cis and in trans with cell adhesion molecules of the immunoglobulin superfamily (IgSF-CAM). At nodes, axonal complexes are composed of Na+ channels and IgSF-CAMs. Schwann cell microvilli, which loosely cover the node, contain ERM proteins and the proteoglycans syndecan-3 and -4. The fundamental role of the cellular contacts in the normal function of myelinated fibers has been supported by rodent models and the detection of genetic alterations in patients with peripheral demyelinating neuropathies such as Charcot-Marie-Tooth diseases. Understanding more precisely their molecular basis now appears essential as a requisite step to further examine their involvement in the pathogenesis of peripheral neuropathies in general.
The present experiments were designed to investigate whether alterations of peripheral nervous system activity may be produced in male Wistar rats by prenatal exposure (from day 0 to day 20 of pregnancy) to relatively low levels of CO (75 and 150 ppm). The voltage clamp analysis of ionic currents recorded from sciatic nerve fibres showed that prenatal exposure to CO produced modifications of sodium current properties. In particular, in 40-day-old rats exposed to CO (75 and 150 ppm) during gestation, the inactivation kinetics of transient sodium current were significantly slowed. Analysis of the potential dependence of steady-state Na inactivation, h infinity (V), showed that the percentage of the maximum number of activable Na channels at the normal resting potential (-80 mV) was increased to approximately 85% in CO-exposed rats. Moreover, the voltage-current relationship showed a negative shift of sodium equilibrium potential in CO treated animals. In 270-day-old CO-exposed rats, parameters of sodium inactivation were not significantly modified; the reversal potential was still lower with respect to controls. The results indicate that prenatal exposure to mild CO concentrations produces reversible changes in sodium inactivation kinetics and on irreversible change in sodium equilibrium potential. These alterations could reflect CO influence on the rate of ion channel development.
Human serum SH2172, obtained from a girl suffering from bullous dermatosis, showed a natural immunoreactivity against the peripheral nervous system (PNS) of rat, mouse and hamster. Immunocytochemical staining and examination by light and electron microscopy demonstrated an intracellular neurofibrillary network localized in neurites and neuronal pericaryons. Comparative testing clearly showed that SH2172 immunoreactivity is different from that of the antibodies against the triplet of proteins NFP70, 160 and 200 kD. This unique serum should be a useful probe to study PNS neurocytoskeleton.
In experiment on rats of Wistar line the type ABA carbonic sorbent, linked with quartzetin, application have promoted less intensive alteration and improvement of reparative regeneration in the peripheric nervous system distal parts in the skin wounds.
HOX11L1 is a homeobox gene involved in peripheral nervous system development as confirmed by knockout mice exhibiting megacolon with enteric ganglia, a phenotype associated in human with Intestinal Neuronal Dysplasia (IND). Using FISH and radiation hybrids we have localized HOX11L1 to human chromosome 2p13.1-->p12, in a 14-cR interval between WI-5987 (D2S2088) and GCT1B4 (D2S2497), and confirmed the synteny between mouse 6C3-D1 and human 2p13.1-->p12 chromosomes by mapping an EST cDNA clone corresponding to mouse HOX11L1 (Tlx2).
To assess the effects of vibrating-tool operation on the autonomic and peripheral nervous system, we measured the variability in the electrocardiographic R-R interval (CVRR) and the distribution of nerve conduction velocities (DCV) in 24 men who were vibrating-tool operators and in 17 healthy adult men (control group). Of the 24 tool operators, 13 had a history of vibration-induced white finger [VWF(+) group] and 11 had no such history [VWF(-) group]. Two components of CVRR, i.e. C-CVRSA and C-CVMWSA, which have been considered to reflect parasympathetic and sympathetic activities, respectively, were also examined. Both the CVRR and the C-CVRSA in the VWF(+) group and the CVRR in the VWF(-) group were found to be significantly depressed as compared with the control values; moreover, a significant difference in the C-CVRSA was observed between the VWF(+) group and the VWF(-) group. The faster DCVs and the sensory median nerve conduction velocity were significantly slowed in the VWF(+) and VWF(-) groups. The C-CVMWSA was significantly correlated with most of the DCV parameters and with the median nerve conduction velocities in all 24 vibrating-tool operators. These data suggest that operation of vibrating tools, which involves exposure to combined stressors of local vibration, heavy work, climate, and noise, affects both the faster myelinated nerve-fiber activity and the parasympathetic activity; the sympathetic activity at rest in workers exposed to hand-arm vibration may be related to depression of peripheral nerve conduction.
Two genes were identified for autosomal recessive forms of early onset Parkinson's disease: parkin and DJ-1. We describe 2 siblings with EOPD due to parkin mutations and peripheral neuropathy, which presented as neuropathy with liability to pressure palsies (HNPP) in the index case. RT-PCR experiments revealed that the parkin gene is expressed in sural nerves from both controls and patient with parkin-related disease. Our findings support the view that parkin may play a role in the peripheral nervous system.
The myelin oligodendrocyte glycoprotein (MOG) is a minor CNS myelin-specific protein that is an important candidate autoantigen in multiple sclerosis. We now report that MOG mRNA transcripts are present in the peripheral nervous system of rodents and primates at levels approximately ten-fold lower than in brain as demonstrated by real time PCR. A major source of this signal are Schwann cells which are also shown to express MOG protein within their cytoplasm in vitro by immunohistochemistry. Expression of MOG by Schwann cells associated with tissue innervation may account for the widespread distribution of low levels of MOG mRNA transcripts, and potentially may provide a source of antigen that can influence the composition and function of the MOG-specific immune repertoire.
The sciatic nerve, and the Schwann cells in particular, are able to synthesize progesterone and possess the enzymes forming the 5alpha-reduced and the 3alpha-5alpha-reduced derivatives of progesterone: dihydroprogesterone and tetrahydroprogesterone. Moreover, the progesterone receptor (PR) is present in the sciatic nerve and in Schwann cell cultures. These facts suggest that progesterone and its derivatives might play a role in the control of the synthesis of the two major proteins of the peripheral nervous system (PNS): the glycoprotein Po (Po) and peripheral myelin protein 22 (PMP22). We have shown that: (a) dihydroprogesterone enhances the low mRNA levels of Po in the sciatic nerve of aged male rats; (b) progesterone and its derivatives stimulate the gene expression of Po in the sciatic nerve of adult rats and in Schwann cell cultures; (c) tetrahydroprogesterone increases PMP22 gene expression in the sciatic nerve of adult rats and in Schwann cell cultures. In additional experiments, utilizing agonists and antagonists of PR and GABAA receptor, we have observed that progesterone and its derivatives control Po gene expression via the PR, while tetrahydroprogesterone modulates the expression of PMP22 through the GABAA receptor.