[Alcohol and the peripheral nervous system].
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Alcoholism↗
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Expression of platelet-derived growth factor (PDGF) and PDGF alpha- and beta-receptors in the peripheral nervous system: an analysis of sciatic nerve and dorsal root ganglia.
Previous studies have shown that cultured Schwann cells secrete platelet-derived growth factor (PDGF) and express PDGF receptors which transmit a mitogenic response particularly when their levels are upregulated by elevation of intracellular cAMP. In this study the expression of PDGF and PDGF alpha- and beta-receptors in the peripheral nervous system (PNS) has been examined by studying dorsal root ganglia and sciatic nerve. Using the monoclonal anti-PDGF antibody, PGF-007, relatively high levels of PDGF were detected in cells of the neonatal rat dorsal root ganglia and sciatic nerve. The location and morphology of these cells indicated that they were Schwann cells while neurons of the dorsal root ganglia were less strongly labeled. The levels in Schwann cells declined during the first postnatal weeks. In the adult rat, low levels of PDGF were detected on myelinated nerve fibers while unmyelinated fibers continued to express higher levels of PDGF. Antisera specific for the PDGF alpha- and beta-receptor revealed high levels of both receptors in the neonatal rat PNS. In the adult rat peripheral nerve both receptors were detectable in unmyelinated nerve fibers. The PDGF beta-receptor, but not the alpha-receptor, was detected at low levels on myelinated nerve fibers. Teased nerve preparations, as well as freshly dissociated sciatic nerve cells, were used to substantiate the findings in frozen tissue sections. Neurons of the dorsal root ganglion expressed PDGF and PDGF alpha- and beta-receptors in all the stages of postnatal development examined. These results indicate that PDGF might play a role in the development of the PNS and in maintenance of peripheral neurons.
Animals↗
Specific replacements of pyruvate for trophic support of central and peripheral nervous system neurons.
When embryonic central nervous system neurons are seeded at low densities with Eagle's basal medium supplemented with the serum substitute N1, glucose, and glutamine, neuronal survival for even 24 h requires the additional supply of exogenous pyruvate--and so does the survival of many peripheral nervous system neurons. Pyruvate can be replaced by alpha-ketoglutarate or oxaloacetate, but not by Krebs cycle substrates that are not keto acids. Most other alpha-keto acids tested (though not beta- or gamma-keto acids) also mimic pyruvate. The apparent equivalence to pyruvate of all these compounds includes identical ED50 values (300 microM for embryonic avian fore-brain neurons, 30-40 microM for rat hippocampal neurons), and also identical susceptibilities to the pyruvate-sparing effects of other low-molecular-weight agents present in Dulbecco's modified Eagle's medium or in astroglia conditioned medium. The substitute alpha-keto acids, however--unlike pyruvate, alpha-ketoglutarate, or oxaloacetate--support cell survival only in the presence of alpha-amino acids that transaminate to alpha-ketoglutarate, oxaloacetate, or pyruvate. The alpha-keto acids, therefore, operate as acceptors of amino groups from appropriate donors to generate Krebs cycle-relevant substrates. Consistent with this view, [14C]glutamate did not generate appreciable 14CO2 unless accompanied by a suitable alpha-keto acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Is there any parallelism between lesions of the peripheral nervous system & vascular changes].
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Blood Vessels↗
Effects on the peripheral nervous system of workers' exposure to carbon disulfide.
An evaluation of the effects of occupational exposure to carbon disulfide was performed in a sample of 156 male viscose rayon workers. A composite group of 233 workers drawn from two other artificial fiber plants located on the same premises as the rayon plant was used for comparison. Effects of CS2 on the peripheral nervous system (PNS) were evaluated in ulnar and peroneal nerves using measurements of maximum motor nerve conduction velocity (MCV) and distal latency; and sensory conduction velocity (SCV) in the sural nerve. Self-reported symptoms related to PNS disorders were also obtained from each study participant. Industrial hygiene records showed the rayon workers to have had CS2 exposures that generally had not exceeded 20 ppm. The overall mean number of years of CS2 exposure was 12.1 years (+/- 6.9 S.D.). The viscose rayon workers were divided prior to the study into three groups according to historical mean CS2 levels calculated for job titles, and area and personal CS2 samples were obtained during the conduct of the study to characterize each job. For these three groups the median CS2 levels were measured to be 1.0, 4.1 and 7.6 ppm. The comparison group's median CS2 level approximated 0.2 ppm. Results showed CS2-exposed workers to have small but statistically significant (p less than .05) reductions in sural SCV and peroneal MCV. Other neurophysiological measures consisting of distal latency, residual latency, and muscle or nerve action potential amplitudes showed no significant differences between study groups. A reduction in the ratio of amplitudes of muscle action potentials obtained from peroneal nerve stimulation was significant (p less than .05). Reductions in the peroneal nerve MCV were found to be related, in a dose response sense, to workers' cumulative exposure to CS2. No increase attributable to CS2 was found in the prevalence of symptoms related to PNS disorders. The results from this study generally agree with similar findings from Finland, Sweden and Italy, but at CS2 exposure levels lower than those previously reported for occupational exposure.
Action Potentials↗
Proctolin-like immunoreactivity in the central and peripheral nervous systems of the locust, Locusta migratoria.
Proctolin-like immunoreactivity (PLI) was widely distributed in the locust, Locusta migratoria, within the central, peripheral and stomatogastric nervous systems, as well as the digestive system and retrocerebral complex. Proctolin-like immunoreactivity was observed in cells and processes of the brain and all ganglia of the ventral nerve cord. Of interest, PLI was found in the lateral neurosecretory cells, which send axons within the paired nervi corporis cardiaci II (NCC II) to the corpus cardiacum (CC). The CC contained extensive processes displaying PLI, which continued on within the paired nervi corporis allata (NCA) to the paired corpora allata (CA) where the axons entered and branched therein. The frontal and hypocerebral ganglia of the stomatogastric nervous system contained PLI within processes, resulting in a brightly staining neuropile. Each region of the gut contained PLI in axons and processes of varying patterns and densities. The paired ingluvial ganglia contained PLI, including an extensively stained neuropile and immunoreactive axons projecting through the nerves to the foregut. The hindgut contained PLI within longitudinal tracts, with lateral projections originating from the 8th abdominal ganglion via the proctodeal nerve. The midgut contained PLI in a regular latticework pattern with many varicosities and blebs. No difference in PLI in cells and processes of the central nervous system (CNS) was found between males and females.
Animals↗
Primary structure of high molecular weight tau present in the peripheral nervous system.
The tau proteins are a family of brain microtubule binding proteins that are required during axonal outgrowth and are found in neurofibrillary tangles in Alzheimer disease. A protein of higher molecular weight, immunologically related to tau, is expressed in the adult peripheral system and in cultured neuronal cell lines of neural crest origin. The predicted amino acid sequence of the high molecular weight tau from N115 cells has been determined from the sequence of its 2340-base-pair cDNA. High molecular weight tau contains an open reading frame encoding 733 amino acid residues. It contains sequences homologous to those present in the N-, middle, and C-terminal domains of adult brain tau proteins, including four homologous repeats, which are the tubulin binding sites, and an amino acid stretch, which is present only in the N-terminal domain of the mature brain variants. The middle region contains a previously unidentified nonhomologous stretch of 237 amino acid residues as well as a domain of 66 residues homologous to exon 6 of the bovine gene that is absent in all bovine, rat, and mouse tau cDNAs sequenced so far. A cDNA probe specific to the nonhomologous tau insert hybridizes to the 8- to 9-kilobase tau mRNA in N115 cells but not to the 6-kilobase tau mRNA in brain. Probes for the domains common to brain tau isoforms hybridize to both messages. The sequence of high molecular weight tau protein also suggests that it, like low molecular weight tau, is an elongated hydrophilic molecule. This cDNA should allow us to study the role of the domains specific to these tau forms in the specialization of the peripheral nervous system and for study of their expression in normal and pathological states.
Amino Acid Sequence↗
Laminin--developmental expression and role in axonal outgrowth in the peripheral nervous system of the chick.
The possible role of laminin on axon outgrowth and guidance in vivo was examined by: (1) determining its developmental expression, and relationship to outgrowth of sensory, motor and sympathetic axons in the chick embryo; and (2) evaluating the changes in the pattern of sympathetic preganglionic projections subsequent to injections of laminin, antilaminin and other laminin function blockers (JG22, INO) into their pathways during axon outgrowth. Double immunofluorescent staining for laminin and neurofilaments in peripheral nerves prior to and during initial outgrowth showed no obvious relationship between laminin and potential nerve pathways. Even though weak laminin immunostaining is apparent throughout the mesenchyme through which axons grow, the most prominent laminin immunostaining is on basement membranes of the neural tube, notochord and dermamyotome. However, as peripheral nerves mature, laminin becomes localized to nerve fascicles throughout the peripheral nervous system, beginning with the dorsal and ventral roots, and progressing later to more distal spinal nerves. Microinjections of antilaminin, JG22 (a monoclonal antibody against laminin/fibronectin receptors) and INO (a monoclonal antibody against a laminin-heparan sulfate proteoglycan complex) into the pathway of sympathetic preganglionic axons prior to and during outgrowth had no effect on the spatio-temporal patterns of sympathetic preganglionic projections. An alternate laminin-rich pathway produced by injecting laminin into the region of the sympathetic trunk immediately adjacent but caudal to the T1 spinal level also did not alter the projection of T1 preganglionic axons. These results suggest that laminin may not be crucial to the initial of peripheral axons. The localization of laminin in nerve fascicles in later stages of development suggests instead that laminin may be important in the maintenance of these structures.
Animals↗
Axonally transported proteins associated with axon growth in rabbit central and peripheral nervous systems.
In an effort to determine whether the "growth state" and the "mature state" of a neuron are differentiated by different programs of gene expression, we have compared the rapidly transported (group I) proteins in growing and nongrowing axons in rabbits. We observed two polypeptides (GAP-23 and GAP-43) which were of particular interest because of their apparent association with axon growth. GAP-43 was rapidly transported in the central nervous system (CNS) (retinal ganglion cell) axons of neonatal animals, but its relative amount declined precipitously with subsequent development. It could not be reinduced by axotomy of the adult optic nerves, which do not regenerate; however, it was induced after axotomy of an adult peripheral nervous system nerve (the hypoglossal nerve, which does regenerate) which transported only very low levels of GAP-43 before axotomy. The second polypeptide, GAP-23 followed the same pattern of growth-associated transport, except that it was transported at significant levels in uninjured adult hypoglossal nerves and not further induced by axotomy. These observations are consistent with the "GAP hypothesis" that the neuronal growth state can be defined as an altered program of gene expression exemplified in part by the expression of GAP genes whose products are involved in critical growth-specific functions. When interpreted in terms of GAP hypothesis, they lead to the following conclusions: (a) the growth state can be subdivided into a "synaptogenic state" characterized by the transport of GAP-23 but not GAP-43, and an "axon elongation state" requiring both GAPs; (b) with respect to the expression of GAP genes, regeneration involves a recapitulation of a neonatal state of the neuron; and (c) the failure of mammalian CNS neurons to express the GAP genes may underly the failure of CNS axons to regenerate after axon injury.
Animals↗
Detection of a cell surface antigen found on rat peripheral nervous system neurons and multiple glia: astrocytes, oligodendrocytes, and Schwann cells.
A cell surface component has been identified that is found on cultured rat dorsal root ganglion neurons and Schwann cells and also cultured brain astrocytes and oligodendrocytes. This component was detected with a monoclonal antibody originally generated to the NG108 (N18 mouse neuroblastoma X C6 rat astrocytoma) hybrid cell line. The antibody, designated B2C11, binds to cultured peripheral nervous system cells: intact dorsal root ganglion and trigeminal neurons and cultured dorsal root ganglion and sciatic nerve Schwann cells. The binding of B2C11 to dorsal root ganglion neurons in vivo was confirmed by immunofluorescence analysis of cryostat sections. However, cultured embryonic rat central neurons showed no detectable binding of B2C11. Cultured brain cells containing glial fibrillary acidic protein (astrocytes) and also oligodendrocytes cultured from corpus collosum did bind B2C11 on their surfaces. B2C11 immunoprecipitation of detergent-solubilized membrane proteins from both lactoperoxidase iodinated C6 and PC12 rat pheochromocytoma cells indicated a single band with an apparent molecular weight of 21,000-23,000. Analysis of B2C11 binding to particulate protein preparations from adult rat organs showed highest specific activity in dorsal root ganglia. Other neural tissues had substantial binding. Some nonneural tissues (lung, kidney, and small intestine) expressed significant antigen levels, whereas others (heart, liver, and skeletal muscle) had a B2C11 antigen-specific activity less than 5% of that of dorsal root ganglia. Thus the B2C11 antigen is enriched in neural tissues, where it is found on the surfaces of a unique set of neuronal and glial cells.
Animals↗
Type III Machado-Joseph disease in a Japanese family: a clinicopathological study with special reference to the peripheral nervous system.
The clinical and pathological findings in a 58-year-old Japanese man suffering from type III Machado-Joseph disease are reported. The patient became affected at the age of 50 years and presented cerebellar ataxia, progressive external ophthalmoplegia and muscular atrophy, although extrapyramidal signs were never detected throughout the whole course of his disease. His mother, sister and son presented progressive ataxia in the third or fourth decade. The mode of inheritance is considered to be autosomal dominant. Pathological examination revealed severe involvement of the dentato-rubral, ponto-cerebellar and subthalamopallidal systems, spinocerebellar tracts and Clarke's column, cranial motor nuclei including the oculomotor systems and anterior horn cells. The involvement of the substantia nigra was relatively mild, and the nerve cells in the inferior olivary nucleus were well preserved. The distal portion of peripheral nerves was severely damaged. Although the striking feature of Machado-Joseph disease is a considerable variability in the individual clinical expression, there have not been many autopsied cases of this disease and efforts to clarify the clinico-pathological correlation in each phenotype have scarcely been made. Relatively mild changes in the substantia nigra and severe involvement of the peripheral nervous system, as in our case, may be the pathological hallmarks of the type III disorder.
Adult↗
Distribution of tau proteins in the normal human central and peripheral nervous system.
In human brain, antibodies to tau proteins primarily label abnormal rather than normal structures. This might reflect altered immunoreactivity owing to post-mortem proteolysis, disease, or species differences. We addressed this issue by comparing the distribution of tau in bovine and human post-mortem nervous system tissues and in human neural cell lines, using new monoclonal antibodies (MAb) specific for phosphate-independent epitopes in bovine and human tau. In neocortex, hippocampus, and cerebellum, immunoreactive tau was widely expressed but segregated into the axon-neuropil domain of neurons. In spinal cord and peripheral nervous system, tau immunoreactivity was similarly segregated but less abundant. No immunoreactive tau was detected with our MAb in glial cells or in human neural cell lines that express neurofilament or glial filament proteins. Post-mortem delays in tissue denaturation of less than 24 hr did not affect the distribution of tau, but the method used to denature tissues did, i.e., microwave treatment preserved tau immunoreactivity more effectively than chemical fixatives such as Bouin's solution, and formalin-fixed tissue samples reacted poorly with our anti-tau MAb. We conclude that the distribution of tau proteins in human nervous system is similar to that described in perfusion-fixed experimental animals, and that visualization of normal immunoreactive tau in human tissues is critically dependent on the procedures used to denature post-mortem tissue samples. Furthermore, microenvironmental factors in different neuroanatomical sites may affect the regional expression of tau.
Animals↗
[Silver impregnation of the peripheral nervous system; Weber's metaterminal apparatus and its variations].
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Humans↗
The demonstration of calcium in the axonal granules of the peripheral nervous system of male Schistosoma mansoni by X-ray microanalysis.
A conspicuous feature of freeze-dried cryosections of male Schistosoma mansoni is the presence of groups of electron-dense granules. X-ray analysis in the TEM of these granules shows them, in comparison with the adjacent cytoplasm, to contain significantly greater amounts of sodium and calcium. In glutaraldehyde-fixed material, these granules have been correlated with the membrane-bounded, electron-dense granules found within the axons of the peripheral nervous system.
Animals↗
Cell fate determination in the peripheral nervous system: the sympathoadrenal progenitor.
Studies of postnatal chromaffin cells, sympathetic neurons and Small Intensely Fluorescent (SIF) cells have suggested that these cells develop from a common progenitor, the sympathoadrenal (SA) progenitor, whose fate is determined by the relative levels of nerve growth factor (NGF) and glucocorticoid (GC) in its environment (Unsicker et al., 1978, Proc. Natl. Acad. Sci. USA 75:3498-3502; Doupe et al., 1985a, J. Neurosci. 5:2119-2142). Recent studies have identified such a bipotential SA progenitor in the rat embryo. Surprisingly, this progenitor is initially unresponsive to NGF; neuronal differentiation is instead promoted by fibroblast growth factor (FGF). However, FGF appears to promote NGF responsiveness, suggesting that neuronal differentiation involves a relay or cascade of growth factor action. Furthermore, chromaffin cell differentiation appears to involve two sequential, GC-dependent events: the inhibition of neuronal differentiation and the induction of epinephrine synthesis. The former event is a prerequisite to the latter. Thus both the chromaffin and neuronal pathways of differentiation follow a series of dependent events, involving changes in the responsiveness of SA progenitors to environmental factors. Such changes correlate with changes in antigenic marker expression that can be observed in vivo. In addition to choosing between neuronal and endocrine fates, SA progenitors must also express an appropriate neurotransmitter phenotype. For example, sympathetic neurons can become either noradrenergic or cholinergic. This cholinergic potential is already present in uncommitted SA progenitors, as evidenced by their ability to synthesize acetylcholine. Recent studies suggest that these cells may have yet other developmental capacities, including the ability to synthesize serotonin. This capacity is consistent with the hypothesis that SA progenitors are closely related to progenitors of enteric neurons, an idea supported by recent observations using novel antigenic markers. The SA progenitor may be, therefore, a "master" neuroendocrine progenitor for the peripheral nervous system.
Adrenal Medulla↗
[Computer-assisted evaluation of the status of the peripheral nervous system in alcoholics].
The authors present the principles of work of a computer system destined for evaluation of the results of routine electrophysiological examination of two muscles and four sensory nerves in alcohol-dependent subjects. The range of examinations and the programme based on discrimination analysis make possible, as shown in own investigations, an objective and complete evaluation of the state of the peripheral nervous system in these subjects. The programme is owned by the EMG laboratory of the Institute of Psychiatry and Neurology in Warsaw where it was introduced for clinical diagnosis, but it may be made available to other persons interested in these problems. An electromyograph with a stimulator with current exit averager and minicomputer, e.g. Commodore 64 with a printer are necessary.
Action Potentials↗
Distribution of cannabinoid receptors in the central and peripheral nervous system.
CB1 cannabinoid receptors appear to mediate most, if not all of the psychoactive effects of delta-9-tetrahydrocannabinol and related compounds. This G protein-coupled receptor has a characteristic distribution in the nervous system: It is particularly enriched in cortex, hippocampus, amygdala, basal ganglia outflow tracts, and cerebellum--a distribution that corresponds to the most prominent behavioral effects of cannabis. In addition, this distribution helps to predict neurological and psychological maladies for which manipulation of the endocannabinoid system might be beneficial. CB1 receptors are primarily expressed on neurons, where most of the receptors are found on axons and synaptic terminals, emphasizing the important role of this receptor in modulating neurotransmission at specific synapses. While our knowledge of CB1 localization in the nervous system has advanced tremendously over the past 15 years, there is still more to learn. Particularly pressing is the need for (1) detailed anatomical studies of brain regions important in the therapeutic actions of drugs that modify the endocannabinoid system and (2) the determination of the localization of the enzymes that synthesize, degrade, and transport the endocannabinoids.
Animals↗
Expression of the CD44 adhesion molecule in tumours of the central and peripheral nervous system.
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Adult↗