Showing papers on "Nervous system published in 1987"

Induction of c-fos-like protein in spinal cord neurons following sensory stimulation.

Abstract: It has been suggested that the proto-oncogenes c-fos and c-myc participate in the control of genetic events which lead to the establishment of prolonged functional changes in neurons. Expression of c-fos and c-myc are among the earliest genetic events induced in cultured fibroblast and phaeochromocytoma cell lines by various stimuli including growth factors, peptides and the intracellular second messengers diacylglycerol, cAMP and Ca2+. We report here that physiological stimulation of rat primary sensory neurons causes the expression of c-fos-protein-like immunoreactivity in nuclei of postsynaptic neurons of the dorsal horn of the spinal cord. Activation of small-diameter cutaneous sensory afferents by noxious heat or chemical stimuli results in the rapid appearance of c-fos-protein-like immunoreactivity in the superficial layers of the dorsal horn. However, activation of low-threshold cutaneous afferents results in fewer labelled cells with a different laminar distribution. No c-fos induction was seen in the dorsal root ganglia, gracile nucleus or ventral horn. Thus, synaptic transmission may induce rapid changes in gene expression in certain postsynaptic neurons.

Lineage analysis in the vertebrate nervous system by retrovirus-mediated gene transfer.

Abstract: We describe a cell-lineage marking system applicable to the vertebrate nervous system. The basis of the technique is gene transfer using the retroviral vector system. We used Escherichia coli beta-galactosidase as a marker gene and demonstrate a high level of expression of this marker from the viral long terminal repeat promoter, with simultaneous expression of the Tn5 neo gene from the simian virus 40 early promoter. This expression has allowed us to detect individual infected cells histochemically. We applied this marking technique to the study of lineage relationships in the developing vertebrate nervous system, both in vivo and in culture. In the rat retina, we injected virus in vivo and histochemically identified clones of marked neural cells. In addition, we used this virus to infect cultures of rat cerebral cortex and have analyzed the clonal relationships of morphologically different neural cell types. The host range of the marking system extends to avian as well as mammalian species. Thus, this system should have broad applicability as a means of gene transfer and expression in the nervous system.

Kindling stimulation induces c- fos protein(s) in granule cells of the rat dentate gyrus

Abstract: Alterations in neuronal gene expression have been proposed to account for permanent changes in brain function such as learning and memory. In particular, it has been suggested that protooncogenes such as c-fos may be rapidly induced in conditions that lead to neuronal plasticity and evoke permanent changes in the expression of effector genes. Concentrations of the c-fos proto-oncogene increase rapidly following depolarization-induced calcium influx in non-dividing neuronally differentiated PC 12 cells. Recently, the presence and induction of c-fos in the adult brain and spinal cord has been observed. Here we report that electrically-induced seizure activity, which leads to a permanent increase in the response of the brain to future seizures (kindling), rapidly and transiently increases c-fos protein-like immunoreactivity in the nuclei of granule cells in the rat dentate gyrus. These results suggest that c-fos protein is present within the nuclei of adult mammalian neurons, and could be involved in plastic changes in the nervous system associated with seizure activity.

Cloning of complementary DNA for GAP-43, a neuronal growth-related protein

Abstract: GAP-43 is one of a small subset of cellular proteins selectively transported by a neuron to its terminals. Its enrichment in growth cones and its increased levels in developing or regenerating neurons suggest that it has an important role in neurite growth. A complementary DNA (cDNA) that encodes rat GAP-43 has been isolated to study its structural characteristics and regulation. The predicted molecular size is 24 kilodaltons, although its migration in SDS-polyacrylamide gels is anomalously retarded. Expression of GAP-43 is limited to the nervous system, where its levels are highest during periods of neurite outgrowth. Nerve growth factor or adenosine 3',5'-monophosphate induction of neurites from PC12 cells is accompanied by increased GAP-43 expression. GAP-43 RNA is easily detectable, although at diminished levels, in the adult rat nervous system. This regulation of GAP-43 is concordant with a role in growth-related processes of the neuron, processes that may continue in the mature animal.

Demonstration of the retrograde transport of nerve growth factor receptor in the peripheral and central nervous system

Abstract: NGF acts on responsive neurons by binding to specific NGF receptors on axonal termini, after which a critical biochemical signal is retrogradely transported to the cell body. The identity of the signal(s) is unknown; candidates include NGF itself or some other "second messenger." A possible second messenger is the NGF receptor. As a first step in assessing the possible role of NGF receptor in the generation of the NGF-dependent signal, and in understanding the economy of NGF receptor synthesis and utilization, we determined whether the NGF receptor is retrogradely transported. Using immunohistochemical staining with a monoclonal antibody (192-IgG) against rat NGF receptor, we looked for accumulation of NGF receptor molecules distal (retrograde transport), as well as proximal (anterograde transport), to sites of axonal ligation or transection. By 10-12 hr in both the ligated sciatic nerve and the lesioned fimbria-fornix, accumulated NGF receptor was detected proximal and distal to the ligation/lesion site. The transported receptor presumably was located in sympathetic and sensory neurons in the sciatic nerve and in forebrain cholinergic neurons projecting from the medial septum to the hippocampus. In both anatomical sites, accumulation of NGF receptor on the proximal (anterograde) side occurred in streams of fine axonal processes, whereas staining on the distal (retrograde) side occurred in varicose or granular configurations. These results raise the possibility that the NGF receptor has a role in the mechanism of NGF beyond the initial binding event at the plasma membrane of the axonal terminus.

Evidence that endogenous beta nerve growth factor is responsible for the collateral sprouting, but not the regeneration, of nociceptive axons in adult rats.

Abstract: A key role has not yet been identified for beta nerve growth factor (NGF) in the growth responses that continue to be expressed in the sensory neurons of adult animals. We have now examined the effects of daily administration to adult rats (and in a few experiments, mice) of antiserum to NGF on (i) the collateral sprouting of undamaged nociceptive nerves that occurs into denervated adjacent skin and (ii) the regeneration of cutaneous sensory axons that occurs after they are damaged. The results were unexpected. All collateral sprouting was prevented and that already in progress was halted; sprouting resumed when treatment was discontinued. In contrast, the reestablishment, and even enlargement, of cutaneous nerve fields by regenerating axons was unaffected by anti-NGF treatment, even after dorsal rhizotomy was done to eliminate any central trophic support. In denervated skin, regenerating and collaterally sprouting axons utilized the same cellular pathways to establish functionally identical fields, thus displaying apparently identical growth behaviors, yet anti-NGF treatment clearly distinguished between them. We suggest that endogenous NGF is responsible for the collateral sprouting of nociceptive axons, probably reflecting an ongoing function of NGF in the regulation of their fields. This demonstration in the adult sensory system of a defined role for NGF in nerve growth could apply to nerve growth factors generally in the adult nervous system. The regeneration, however, of nociceptive axons (and nonnociceptive one) is not dependent on NGF.

Morphological differentiation of the embryonic peripheral neurons in Drosophila

Abstract: The stereotyped segmental and dorso-ventral organization of the peripheral nervous system (PNS) of Drosophila embryos allows the identification of all the neurons in the body wall. Distinct classes of neurons are distinguishable according to their location, the targets they innervate, the particular shape of their dendrites and their cell size. Those neurons innervating external sensory structures (es) and chordotonal organs (ch) have single dendrites and have been previously described (Ghysen et al. 1986; Dambly-Chaudiere and Ghysen 1986; Campos-Ortega and Hartenstein 1985). We describe here the identity and morphological features of three other classes of neurons in the body segments which have multiple dendrites (md neurons): 1) neurons that give rise to elaborate dendritic arborisations (da neurons); 2) neurons that have bipolar dendrites (bd neurons); 3) neurons that arborize around particular tracheal branches (td neurons). The thoracic hemisegment (T2 and T3) contains 13 da, one bd, one td, 21 es and four ch neurons; the abdominal hemisegment (A1 to A7) contains 14 da, three bd, three td, 15 es and eight ch neurons. The arrangement of the segmented peripheral neurons is highly invariant and provides a favorable assay system for the genetic analysis of neurodevelopment.

Ontogeny of the calcium binding protein calbindin D-28k in the rat nervous system.

Abstract: Calbindin D-28k immunoreactivity appeared at embryonal day 14 (E14) in the central nervous system as well as in the sensory organs and at E15 in the peripheral nervous system of the rat. At E14 the infundibular process of the diencephalon, cells of the posterior hypothalamus and of the dorsal thalamus were the only structures strongly immunostained in the brain, whereas neurons of the basal plate of the spinal cord, medulla oblongata and of the out-ermost layer of the cerebral cortex were only faintly labeled. Calbindin positive cerebellar Purkinje cells could be discerned at E15 together with a few cells in the hippocampus and in ganglia of the cranial nerves. At E19 various mesencephalic and metencephalic structures, spinal ganglion cells and basal ganglia displayed calbindin immunoreactive cells. The adult pattern of calbindin immunoreactivity (Garcia Segura et al. 1984) was reached before birth in most brain regions. In general, cells which displayed calbindin during brain development were also calbindin positive in the adult animal. Exceptions to this rule were cells of the deep nuclei of the cerebellum and non-neuronal cells which transiently expressed calbindin during development. Calbindin appeared in a given brain region almost invariably 1 or 2 days after the cessation of cell division and the beginning of neuronal migration and extension of neuronal processes. The calcium binding protein calbindin might influence these Ca2+-dependent processes.

Nerve fiber growth in culture on tissue substrata from central and peripheral nervous systems

Abstract: In adult mammals, injured neurons regenerate extensively within the PNS but poorly, if at all, within the CNS. We have studied the effect of substrata consisting of tissue sections from various nervous systems on nerve fiber growth in culture and correlated our results with the growth potential of these tissues in vivo. Ganglionic explants from embryonic chicks (9–12 d) fail to extend nerve fibers onto sections of adult rat optic nerve or spinal cord (CNS) but do so on sciatic nerve (PNS). Dissociated DRG neurons behave similarly whether in serum- containing or defined medium. Tissue substrata from nervous systems that support regeneration in vivo--i.e., goldfish optic nerve, embryonic rat spinal cord, degenerating sciatic nerve--also support fiber growth in culture. Within the same culture, neurons will grow onto sciatic nerve rather than neighboring optic nerve sections, suggesting that the responsible agent(s) is not soluble. In addition, neurons adhere more extensively to sciatic nerve substrata than to optic nerve. The occurrence of 3 molecules known to be involved in neuron-substratum adhesion and nerve fiber growth in vitro has been documented immunocytochemically in the tissue sections. One of these, laminin, is demonstrable in all tissues tested that supported nerve fiber growth. Immunoreactivities for fibronectin and heparan sulfate proteoglycan are found in only some of these tissues. None of these 3 molecules can be demonstrated in neural cells of normal adult rat CNS tissue. Our data suggest that these molecules may be important effectors of nerve regeneration in neural tissues.

Distribution and partial characterization of FMRFamide-like peptides in the stomatogastric nervous systems of the rock crab, Cancer borealis, and the spiny lobster, Panulirus interruptus.

Abstract: The distribution of FMRFamide-like peptides was studied in the complete Stomatogastric nervous system [the paired commissural ganglia, single oesophageal ganglion, and the single Stomatogastric ganglion (STG)] of two decapod crustacean species, the spiny lobster Panulirus interruptus and the rock crab Cancer borealis, by using immunocytochemical techniques. Antiserum 231 from the O'Donohue laboratory and antiserum 671C (described here) gave essentially the same staining patterns. In the commissural ganglia of both species there were ten to 20 stained neurons and dense neuropilar staining. The oesophageal ganglion of the crab had four stained neurons. Lucifer Yellow backfills followed by immunostaining showed that the two larger stained neurons of the oesophageal ganglion sent processes into the inferior ventricular nerve. The two smaller neurons sent processes into the inferior oesophageal nerves. The oesophageal ganglion of the lobster had two stained neurons that sent processes into the inferior ventricular nerve as well. None of the somata of the STG stained in either species, but in both species stained fibers were seen in the Stomatogastric nerve that entered the STGs and ramified profusely throughout the neuropil. In some preparations of the crab, a stained fiber was visible in the dorsal ventricular nerve. The amounts of the FMRFamide-like peptides found in all regions of the nervous system of P. interruptus and C. borealis were determined by radioimmune assay (RIA). Column chromatography and high-performance liquid chromatography suggest that, in both species, much if not all of the RIA-assayable material is accountable for by peptides that are larger and more hydrophobia than FMRFamide.

Immune reactivity in the nervous system: modulation of T-lymphocyte activation by glial cells.

Abstract: The vertebrate central nervous system (CNS) has been traditionally thought to be inaccessible for the passenger lymphocytes of the immune system. This does not seem to be the case: activated T-lymphocytes can readily cross the endothelial blood-brain barrier (BBB) and some glial cells, notably the astrocytes, seem to be programmed to act as most efficient and complex partners for antigen-specific T-lymphocytes. We used myelin basic protein (MBP) specific permanent rat T-lymphocyte lines as probes to assess the immune status of the CNS. These cells, upon activation in vitro, are able to transfer lethal, experimentally induced autoimmune-encephalomyelitis (EAE) to normal syngeneic recipients. Activated T-lymphocytes, but not resting ones, can break through the BBB irrespective of their antigen specificity. Immune surveillance of the CNS thus seems to be executed by activated T-lymphocytes. Having crossed the BBB, the activated T-cells interact with local glial cells by releasing factors, including interferon-gamma, which induced astrocytes to synthesize and express, on their membranes, class II major histocompatibility antigens (Ia determinants), which are critically required for immunogenic presentation of antigens to T-cells. Indeed, Ia-induced astrocytes of the CNS (and the Schwann cells of peripheral nerves) are efficient antigen presenter cells, which are able strongly to up-regulate antigen-reactive T-lymphocytes. In addition, it has recently been shown that at least some astrocytes are able to down-regulate immune cells. Some, but not all, astrocytes are capable of suppressing activation of T-cells. This suppression can be modulated by interferon-gamma, and is sensitive to irradiation. The question of whether suppression is mediated by direct cell-to-cell contact or via soluble mediators (e.g. apolipoprotein E) is under investigation. Astrocytes have been found to be most subtle regulators of immuno-competent T-cells. Most probably they are centrally involved in physiological immune reactivity of the CNS, and it will be tempting to learn how far glial cells are involved in transmitting regulatory signals between the immune and nervous systems.

Developmentally regulated expression of the nerve growth factor receptor gene in the periphery and brain

Abstract: Nerve growth factor (NGF) regulates development and maintenance of function of peripheral sympathetic and sensory neurons. A potential role for the trophic factor in brain has been detected only recently. The ability of a cell to respond to NGF is due, in part, to expression of specific receptors on the cell surface. To study tissue-specific expression of the NGF receptor gene, we have used sensitive cRNA probes for detection of NGF receptor mRNA. Our studies indicate that the receptor gene is selectively and specifically expressed in sympathetic (superior cervical) and sensory (dorsal root) ganglia in the periphery, and by the septum-basal forebrain centrally, in the neonatal rat in vivo. Moreover, examination of tissues from neonatal and adult rats reveals a marked reduction in steady-state NGF receptor mRNA levels in sensory ganglia. In contrast, a 2- to 4-fold increase was observed in the basal forebrain and in the sympathetic ganglia over the same time period. Our observations suggest that NGF receptor mRNA expression is developmentally regulated in specific areas of the nervous system in a differential fashion.

Parallel processing of proprioceptive signals by spiking local interneurons and motor neurons in the locust.

Abstract: The connections made by afferents from a proprioceptor at the femorotibial joint in a hind leg of a locust, the femoral chordotonal organ (FCO), were determined by making intracellular recordings from motor neurons and spiking local interneurons in the central nervous system and from afferent cell bodies in the periphery. Staining the central projections of the afferent neurons with dye introduced into their axons at the receptor, and the intracellular injection of dye into motor neurons and interneurons, shows that the branches of all 3 types of neuron overlap in specific regions of neuropile. Afferents excited by a movement of the receptor apodeme that is equivalent to an imposed extension of the femorotibial joint excite flexor tibiae motor neurons and some spiking local interneurons with cell bodies at the ventral midline of the metathoracic ganglion. The opposite movement excites extensor tibiae motor neurons and a different set of spiking local interneurons. Spikes in afferents that excite flexor motor neurons evoke depolarizing potentials that follow each spike with a consistent central latency of approximately 1.5 msec. The amplitude of the depolarizing potentials is dependent upon the membrane potential of the motor neuron. This evidence points to the connection being direct and to the potentials' being EPSPs. Simultaneous recordings from certain spiking local interneurons and certain flexor motor neurons show that they receive many synaptic potentials in common and are driven in a parallel fashion by movements of the receptor apodeme. Spikes of some afferents evoke EPSPs in both neurons with the same consistency and latency. An afferent can therefore synapse directly upon a motor neuron and a spiking local interneuron. Each afferent synapses on several motor neurons and possibly upon several interneurons. In turn, each motor neuron and each interneuron receives inputs from several afferents.

Rejection of fetal neocortical neural transplants by H-2 incompatible mice.

Abstract: In order to examine questions concerning immunologic privilege of the central nervous system, we placed neocortical transplants into cerebral ventricles of mice. We compared the fates of transplants between fully H-2 compatible (isografts) and H-2 incompatible (allografts) animals. Histologic evaluation comparing animals from iso- and allograft groups revealed significant differences in the number of inflammatory cells and in the degree of necrosis within the grafts. Response to allografted tissue within the brain mimics that seen in several immune-mediated diseases of the nervous system in that neurons appear to be selectively spared. Only upon subsequent stimulation of the host's immune system with an orthotopic skin graft bearing the major histocompatibility complex antigens of the neural graft are neurons destroyed. Immunohistochemical evaluation revealed that the inflammatory cell infiltrates in and around the allografts were composed of Lyt-2+, L3T4+, and Mac-1+ cells. In addition, Ia+ endothelial cells as well as Ia+ parenchymal CNS cells were found in both donor and host tissue of allografted animals. Hence, H-2 incompatible neural tissue transplanted to the CNS is recognized and rejected by the immune system of the recipient animal. The cellular infiltrates seen within the first weeks to months following transplantation of allogeneic CNS tissue resemble those seen in other allografts undergoing rejection. We conclude that the CNS is not unconditionally privileged as either a transplant site or as a source of transplanted tissue.

Biochemistry of information storage in the nervous system.

Abstract: The use of molecular biological approaches has defined new mechanisms that store information in the mammalian nervous system Environmental stimuli alter steady-state levels of messenger RNA species encoding neurotransmitters, thereby altering synaptic, neuronal, and network function over time External or internal stimuli alter impulse activity, which alters membrane depolarization and selectively changes the expression of specific transmitter genes These processes occur in diverse peripheral and central neurons, suggesting that information storage is widespread in the neuraxis The temporal profile of any particular molecular mnemonic process is determined by specific kinetics of turnover and by the geometry of the neuron resulting in axonal transport of molecules to different synaptic arrays at different times Generally, transmitters, the agents of millisecond-to-millisecond communication, are subject to relatively long-lasting changes in expression, ensuring that ongoing physiological function is translated into information storage

Neuropeptide Y-like immunoreactivity in rat cranial parasympathetic neurons: coexistence with vasoactive intestinal peptide and choline acetyltransferase.

Abstract: Neuropeptide Y (NPY) is widely distributed in the sympathetic nervous system, where it is colocalized with norepinephrine. We report here that NPY-immunoreactive neurons are also abundant in three cranial parasympathetic ganglia, the otic, sphenopalatine, and ciliary, in the rat. High-performance liquid chromatographic analysis of the immunoreactive material present in the otic ganglion indicates that this material is very similar to porcine NPY and indistinguishable from the NPY-like immunoreactivity present in rat sympathetic neurons. These findings raise the possibility that NPY acts as a neuromodulator in the parasympathetic as well as the sympathetic nervous system. In contrast to what has been observed for sympathetic neurons, NPY-immunoreactive neurons in cranial parasympathetic ganglia do not contain detectable catecholamines or tyrosine hydroxylase (EC 1.14.16.2) immunoreactivity, and many do contain immunoreactivity for vasoactive intestinal peptide and/or choline acetyltransferase (EC 2.3.1.6). These findings suggest that there is no simple rule governing coexpression of NPY with norepinephrine, acetylcholine, or vasoactive intestinal peptide in autonomic neurons. Further, while functional studies have indicated that NPY exerts actions on the peripheral vasculature which are antagonistic to those of acetylcholine and vasoactive intestinal peptide, the present results raise the possibility that these three substances may have complementary effects on other target tissues.

Metabolites of arachidonic acid in the nervous system of Aplysia: possible mediators of synaptic modulation.

Abstract: Release of arachidonic acid from membrane phospholipids is receptor-mediated and might generate second messengers in neurons. We tested this idea using the simple nervous system of the marine mollusk, Aplysia californica. Aplysia neural components metabolize arachidonic acid through lipoxygenase and cyclo-oxygenase pathways. We identified 2 major lipoxygenase products, 12- and 5-hydroxyeicosatetraenoic acids (12-HETE and 5-HETE), and 2 cyclo-oxygenase products, PGE2 and PGF2 alpha. These metabolites of arachidonic acid are formed in synaptosomes, as well as in identified nerve cell bodies, indicating that both lipoxygenase and cyclo-oxygenase pathways are active within neurons. Application of the modulatory neurotransmitter histamine to cerebral ganglia that had been labeled with 3H-arachidonic acid induced the formation of 3H-12-HETE. This response was inhibited by the histamine antagonist cimetidine. Furthermore, release of radioactive 5-HETE and 12-HETE was observed after intracellular stimulation of the histaminergic cell C2 in cerebral ganglia labeled with 3H-arachidonic acid. Cimetidine also inhibited this response. Application of serotonin or stimulation of the giant serotonergic cell (GCN) in the cerebral ganglion did not cause detectable amounts of the labeled eicosanoids to be released. We found that intracellular stimulation of putative histaminergic neurons in the L32 cluster of the abdominal ganglion, which produces presynaptic inhibition in L10 neurons, also elicited the release of 3H-12-HETE and 3H-PGE2. Thus, for the first time we provide evidence that synaptic stimulation promotes turnover of arachidonic acid in neurons. We suggest that metabolites of arachidonic acid are likely to participate in some postsynaptic responses to histamine and may be second messengers for presynaptic inhibition.

Effect of stimulation of trigeminal ganglion on regional cerebral blood flow in cats.

Abstract: Regional cerebral blood flow was studied in the cat, with and without trigeminal ganglion stimulation, by the intravenous injection of the tracer [14C]iodoantipyrine and subsequent regional brain dissection. Electrical activation of the trigeminal ganglion led to a selective increase in regional blood flow in the frontal and parietal cortex that was bilateral without change in the posterior cortex, deep cerebral nuclei, white matter, or brain stem. Unilateral intracranial section of the facial nerve blocked the response in the ipsilateral frontal and parietal cortex, whereas bilateral facial nerve section blocked the contralateral frontal cortical response. The contralateral parietal cortical increase in blood flow was not affected by facial nerve section and may thus represent the result of metabolic activation of sensory cortex.

Cyclic AMP regulates the proportion of functional acetylcholine receptors on chicken ciliary ganglion neurons.

Abstract: Previous studies have shown that the number of functional acetylcholine receptors (AcChoRs) on chicken ciliary ganglion neurons in culture is considerably smaller than the total number of AcChoRs detected on the neurons by labeled receptor probes. Here we use patch-clamp recording to show that a cAMP-dependent process enhances the AcCho response of the neurons by a mechanism likely to involve an increase in the number of functional AcChoRs. The increase occurs without requiring protein synthesis and without involving a detectable increase in the total number of AcChoRs on the cell surface measured with a labeled receptor probe. The results imply that the neurons have functional and nonfunctional pools of AcChoRs and that functional receptors can be recruited from intracellular receptors or from nonfunctional receptors on the cell surface by a cAMP-dependent process. A cAMP-dependent regulation of the number of functional neurotransmitter receptors would provide a reversible mechanism by which cell-cell interactions could modulate synaptic transmission in the nervous system.

Loss of sensory neurons after sciatic nerve section in the rat

Abstract: In this study, the loss of sensory neurons in the rat was assessed after sciatic nerve section at birth and at 4 weeks of age. The neuronal deficit in ganglia L4-L6, 39-89 weeks after neonatal denervation, was 10,000-17,000. The nerve contains about 19,000 afferent axons, so some axotomized neurons survived. Degenerating perikarya were absent, probably because all surviving neurons had reestablished target contacts. Sectioning the nerve at age 4 weeks, in five rats, after 19-92 weeks had caused the death of 7,000-11,500 neurons. Whether the nerve regenerated or not in these rats apparently did not influence the extent of neuron death. Nevertheless, no deficit was observed in a sixth rat in which muscle reinnervation was very good. Therefore, the results are inconclusive with respect to the effect of axonal regeneration. Ganglia of rats operated at age 4 weeks regularly contained perikarya with axonal reaction; this supports the notion that some mature neurons are able to permanently survive without target contact. There was no evidence for selective loss of large or small neurons after nerve section at birth or at age 4 weeks. The extent of cell loss in individual ganglia varied, indicating varying contributions of the three ganglia to the nerve. Hence, it is not possible to quantify the effect of experimental conditions on the number of sensory neurons when only one of the several ganglia contributing to the nerve is investigated.

Contribution of the nervous system to the pathophysiology of rheumatoid arthritis and other polyarthritides.

Abstract: Some clinical features of rheumatoid arthritis (RA) (for example, preferential joint involvement and bilateral symmetry), taken together with the strong evidence of neurogenic inflammatory processes, suggest that the nervous system contributes to the inflammatory component of RA and other polyarthritides. The authors propose that the increased risk and severity of disease in particular joints reflects a greater innervation of those joints by unmyelinated afferent and sympathetic efferent fibers. Release of the proinflammatory peptide, substance P, from the peripheral terminals of nociceptive joint afferent fibers, through interactions with many nonneural cells, exacerbates the inflammatory process. Release of mediators from sympathetic efferents (including norepinephrine) also contributes to the inflammation, either through an independent mechanism or by acting in concert with the nociceptive afferent-derived substances. Therapies directed at interruption of the nervous system contribution to the pathophysiology of these diseases should offer a new direction to treatment.

Neurobiology of the Echinodermata

Abstract: There has been little progress since the classical anatomical studies in understanding the form and function of the nervous system of echinoderms until relatively recently. There is, admittedly, a substantial behavioural literature but much of this can be confusing and even contradictory. There were early attempts to record electrical activity with extracellular electrodes but the compound potentials recorded to gross stimulation were clearly highly artifactual. Brehm (1977) showed that it was possible to record single unit activity extracellularly and further that this was possible because the brittlestar preparation that he used contained neurones much larger than average. Since then the large neurones of brittlestars have been exploited to produce a growing amount of information about function in echinoderm nervous systems at the cellular level. It is possible to use multiple recording sites from intact animals and monitor the activity that co-ordinates behaviour. There is data on the sensory perception of a range of environmental parameters. These direct electrophysiological measurements of response to stimuli are invariably consistent and are thus much more valuable than the inconsistent behavioural criteria previously used. It is also now possible to record intracellularly from both ectoneural neurones and hyponeural neurones. Lucifer yellow can be injected iontophoretically into both classes of neurones and preliminary data has now been obtained on the general morphology of individual cells within the nervous system (Cobb 1985). The radial nerve cords consist of connected segmental ganglia. The layout of the large neurones in each segmental ganglia is similar whatever the position of the ganglia within the radial nerve cords. Longitudinally running large neurones pass through at least 4 or 5 segments and show a fine plexus of varicose terminals at each end. These neurones are multimodal in the information they transmit about changes in the environment. The circumoral ring does not show complex structure but appears to act as a connection between the radial nerve cords and does not appear to contain organizing centres. The present evidence suggests that any part of the radial nerve cords when receiving significant local sensory input can act to coordinate whole animal behaviour and thus the echinoderms can be considered “brainless”.

Immunohistochemistry and biosynthesis of N-acetylaspartylglutamate in spinal sensory ganglia.

Abstract: N-Acetylaspartylglutamate (NAAG) is a nervous system-specific dipeptide which has been implicated in chemical neurotransmission. Antisera were prepared against NAAG in order to study its cellular distribution. When these antisera were applied to tissue sections of rat spinal sensory ganglia, NAAG-like immunoreactivity was detected within a subpopulation of relatively large neuronal cell bodies in cervical, lumbar, and thoracic ganglia. In order to confirm the presence of NAAG within these neurons, the dipeptide was extracted and purified from spinal ganglia using high-performance liquid chromatography and its composition confirmed by amino acid analysis. Further, the biosynthesis of NAAG was studied in vitro by following the incorporation of either [3H]glutamine or [3H]glutamate into the glutamate residue of the purified dipeptide. [3H]Aspartate was not incorporated efficiently into NAAG under these conditions, suggesting a precursor role for the large N-acetylaspartate pool. The incorporation of radiolabeled amino acids into newly synthesized NAAG by spinal sensory ganglia was not inhibited by incubation of the cells with anisomycin or cycloheximide at concentrations which significantly inhibited protein synthesis. These data suggest that NAAG is present in a subpopulation of primary afferent spinal neurons and that its biosynthesis is mediated by a dipeptide synthetase.

Stimulatory effect of He-Ne low dose laser on injured sciatic nerves of rats.

Abstract: Injury to a mammalian peripheral nerve is accompanied by a restorative process that is manifested after a delay. This process is expressed morphologically by the emergence of new nerve fibers. Restoration of function occurs when the regenerating fibers reconnect with the target organ. Because of the low rate of fiber elongation, the denervated target is partially degenerated by the time that the regenerating fibers approach it. To prevent such an atrophy, one must find a way to prevent the degeneration of the nerve, to speed up regeneration, or to maintain the target during the period of nerve degeneration. In the present work, we examined the potential of treatment with low energy laser radiation for improving regeneration or preventing degeneration of mammalian peripheral nerve after injury. After repeated injury for 20 consecutive days, treatment of the sciatic nerve of the rat with low energy laser (He-Ne, 17 mW) caused a significant increase in the amplitude of the action potential recorded in the corresponding gastrocnemius relative to the action potential of injured but not treated nerves. The action potential of the injured sciatic nerves that were laser-irradiated increased to values close to that of a noninjured nerve. The studies include follow-up for 1 year after the injury. This electrophysiological manifestation of the effect of laser treatment on injured nerves was accompanied by a diminution of the size of the scar tissue from these nerves. Yet to be resolved is whether these two phenomena (i.e., electrophysiological and morphological responses) coincide or whether they relate to each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Neural cell adhesion molecule in normal, denervated, and myopathic human muscle.

Abstract: The neural cell adhesion molecule (N-CAM) is a cell-surface glycoprotein that may mediate some intercellular adhesive interactions in the nervous system. In adult rat muscle, N-CAM is concentrated near neuromuscular junctions and on satellite cells, but is nearly undetectable in nonsynaptic portions of myofibers. However, N-CAM is abundant throughout myofibers in denervated and regenerating muscles. Using affinity-purified antibodies to N-CAM, we were able to demonstrate a similar distribution and regulation of N-CAM in human muscle. Myofiber N-CAM was not detectable immunohistochemically in any of 10 normal biopsies or in 4 biopsies that were abnormal but showed no evidence of fiber denervation or regeneration. N-CAM was present, however, at end plates, nerves, and satellite cells in normal human muscle. In contrast, myofiber N-CAM was detected in 16 of 16 patients with histological evidence of denervation and in 10 of 10 patients who had myopathy with degenerating/regenerating myofibers. In addition, 2 of 2 histologically nondiagnostic biopsies from patients with amyotrophic lateral sclerosis contained N-CAM-positive myofibers. Immunoblot analysis also detected N-CAM in denervated and myopathic, but not normal, human muscle. These results suggest that N-CAM may play a role in muscle reinnervation or regeneration and that N-CAM immunohistochemistry may complement conventional techniques in the diagnosis of neuromuscular disease.