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At least 811 records · Page 45Linked to original sources

Segment-specific expression of a zinc-finger gene in the developing nervous system of the mouse.

The process of segmentation, in which repeated homologous structures are generated along the anterior-posterior axis of the embryo is a widespread mechanism in animal development. In vertebrates, segmentation is most apparent in the somites and the peripheral nervous system, but the existence of repetitive bulges, termed neuromeres, in the early neural epithelium of vertebrates suggests that the CNS may also be segmented. Consistent with this, cranial ganglia and certain neurons are associated with specific hindbrain neuromeres. Here, we report that Krox-20, a zinc-finger gene, is expressed in two alternate neuromeres in the mouse early hindbrain. This pattern subsequently decays and Krox-20 is transiently expressed in specific hindbrain nuclei. In addition, Krox-20 is expressed in early neural crest cells, and then in the neural crest-derived boundary caps, glial components of the cranial and spinal ganglia. The demonstration that neuromeres are domains of gene expression provides molecular evidence for the segmentation of the CNS.

Animals↗

[Neuronal apoptosis in the central and peripheral nervous system in HIV infection].

Apart from the unique changes characteristic of "HIV encephalitis", the productive infection of central nervous system by HIV, which predominantly involves the white matter and basal ganglia, evidence is accumulating that the cerebral cortex may also be affected in AIDS patients. Neuronal loss, suspected at microscopic examination, has been demonstrated by a number of morphometric studies. However, the cause and mechanism of neuronal damage in HIV infection, are still unclear. In an attempt to look for an apoptotic process at the origin of neuronal loss in AIDS, we examined samples of frontal cortex, temporal cortex and basal ganglia from 12 patients who died from AIDS and 4 asymptomatic HIV-positive cases using in situ end labelling to demonstrate characteristic DNA fragmentation. These were compared with 5 asymptomatic seronegative controls, and 2 seronegative patients with Alzheimer's disease. We demonstrated neuronal apoptosis in all AIDS cases and in the Alzheimer's cases. Positive in situ end labelling was usually associated with morphological changes suggestive of neuronal apoptosis. Semiquantitative assessment of the density of apoptotic neurons showed that neuronal apoptosis was more severe in atrophic brains. In contrast, no correlation was found between the density of apoptotic neurons and the presence of HIV-encephalitis or a history of cognitive disorder. Only occasional apoptotic neurons were found in one asymptomatic, HIV-positive case. Apoptosis was never observed in asymptomatic seronegative cases. We also looked for apoptotic neurons in spinal ganglia of 20 AIDS cases, 5 of whom had a terminal sensory distal neuropathy, and 10 seronegative controls devoid of neuropathy. Apoptotic neurons were found in 6 of the AIDS patients and in none of the seronegative controls. However, no correlation was found between the severity of neuronal apoptosis in the spinal root ganglia and the presence of absence of a terminal distal sensory neuropathy. Experimental studies tend to support our in vivo findings. HIV-infection of primary cultures of human embryonic central nervous system induced frequent apoptosis of neurons. No apoptotic cell was identified in non infected control cultures.

AIDS Dementia Complex↗

Central nervous system signs in chickens caused by a new avian reovirus strain: a pathogenesis study.

The present study describes the pathogenesis of infection of chicks with a new avian reovirus strain, belonging to the so-called enteric reovirus strains (ERS) that is capable of causing central nervous system signs in SPF white leghorns. After intramuscular (IM) or oral inoculation birds were either observed for clinical signs or sacrificed for macroscopic, histological and virological examination for 21 days. Virus isolation was performed on the brain, leg muscle, hock joint, liver and spleen. For the detection of viral antigen the immunohistochemistry (IHC) technique was performed on the caudal part of the cerebrum, spinal cord including spinal ganglia and right N. Ischiadicus. High mortality (79% in 7 days) was seen in birds that were inoculated IM. Survivors were depressed and stayed small until the end of the experiment. One bird had tremor and showed torticollis at 9 days after IM inoculation. Birds that were inoculated orally were depressed from day 4 and stayed small until the end of the experiment. One bird showed a torticollis at 10 days after inoculation. After both IM and oral inoculation ERS was isolated from the brain between 3 and 10 days after inoculation. Other examined organs were positive for virus isolation from day 1 or 5 until day 21. IHC revealed viral antigen positive cells in the Plexus chorioideus (plexus epithelial cells or cells within the underlying connective tissue) and in a spinal ganglion. The results indicate that the pathogenesis of ERS infection in chickens bears some resemblance with that of the mammalian reoviruses serotype 1 in mice.

Animals↗

Effect of exposure to anti-NGF on sensory neurons of adult rats and guinea pigs.

Nerve growth factor (NGF) deprivation was produced in adult rats and guinea pigs by immunization against mouse NGF. Exposure of adult animals to anti-NGF had no effect on sensory ganglion neuronal number or size-frequency histograms. However, the substance P content of sensory ganglia, spinal cord and hind paw skin decreased to as great an extent as was seen in animals exposed to anti-NGF in utero. We conclude that NGF has two separate effects on sensory neurons: adult sensory neurons require NGF for normal function whereas developing neurons require NGF for both survival and transmitter expression.

Animals↗

Biosynthesis, axonal transport and turnover of neuronal substance P.

In dorsal root ganglia substance P is synthesized ribosomally, probably via a precursor. A second peptide, apparently a modified form of substance P (8-11), is cosynthesized with substance P and transported with it down both dorsal roots and peripheral branches. Four times as much substance P-like immunoreactivity is transported peripherally as centrally. Only 30% of axonal substance P-like immunoreactivity is available for rapid axonal transport and this is transported at a rate of 4.9 mm h-1. Axonal transport is not necessary for substance P synthesis. Doses of anisomycin which inhibit CNS protein synthesis by more than 95% do not cause any fall in substance P levels over an eight-hour period in ganglia, spinal cord or brain, suggesting that turnover is slower than that of conventional transmitters. However, stimulation of the hindlimbs of these animals reduces substance P levels in the dorsal horn. The turnover rate of spinal cord substance P, estimated either by relating the amount transported down dorsal roots to that in terminals or by measuring the decline of substance P levels after intrathecal colchicine, is four to five days. The functional organization of the substance P neuron is discussed with particular reference to the maintenance of peptide levels in terminals.

Amino Acids↗

Distribution of the 75-kD low-affinity nerve growth factor receptor in the primate peripheral nervous system.

Disruption of the 75-kD low-affinity nerve growth factor (NGF) receptor (p75) has been shown to result in sensory and sympathetic nervous system deficits (Lee et al., 1992a,b). In order to establish precisely which subsets of neurons are capable of responding to neurotrophins (NTs) through the low-affinity NGF receptor, p75 was localized in the primate autonomic and somatic sensory nervous systems. In the autonomic system, cell bodies of some parasympathetic and enteric neurons expressed detectable levels of p75, whereas all sympathetic neurons expressed the protein. In the sensory system, some, but not all, cell bodies were labeled in cranial and spinal sensory ganglia and in the mesencephalic nucleus. Some peripheral and central projections of the sensory neurons were also labeled. Centrally, most of the labeled processes were found in regions containing primarily small unmyelinated fibers, including lamina II of Rexed and areas of the solitary tract and nucleus. Peripherally, labeled processes were associated with unmyelinated nerves and specialized structures such as taste buds and Meissner corpuscles, but not with myelinated processes. This study indicates that the subset of neurons in the autonomic nervous system likely to be capable of responding to neurotrophins is broader than generally thought, and that p75-expressing neurons tend to be clustered. Moreover, in the sensory nervous system p75 is expressed by most cell bodies, but expression in their projections is restricted both peripherally and centrally to unmyelinated processes and nerve terminals.

Animals↗

Adrenalectomy increases the number of substance P and somatostatin immunoreactive nerve cells in the rat lumbar dorsal root ganglia.

Using an immunocytochemical technique we have analyzed changes in substance P, somatostatin, calcitonin gene-related peptide, and galanin immunoreactivity pattern in the rat dorsal root ganglia. After 7 days of adrenalectomy, sham operated rats were compared with adrenalectomized animals either receiving a daily intraperitoneal injection of 10 mg/kg b.wt. corticosterone or vehicle. Three lumbar ganglia from each animal were blocked, serially cut, and immunostained for each neuropeptide by means of the biotin-avidin-peroxidase technique. A systematic sampling of immunoreactive ganglion cells was performed and the sample number of immunoreactive ganglion cells was calculated. After adrenalectomy, the number of substance P and somatostatin immunoreactive ganglion cells markedly increased ((means +/- S.E.M.): 245 +/- 68 versus 123 +/- 12 for sham operated animals, P < 0.01 (substance P) and 42 +/- 8 as compared to 22 +/- 9 for sham operated animals, P < 0.01 (somatostatin)). No significant changes were found in the number of calcitonin gene-related peptide and galanin immunoreactive cells after adrenalectomy. These results suggest that adrenal steroid hormones may reduce the synthesis of both substance P and somatostatin in the dorsal root ganglion cells. Daily treatment with a high dose of corticosterone, mimicking its serum levels after stress, failed to prevent the increase of peptide contents after adrenalectomy. These observations also indicate that a tonic action of corticosterone on mineralocorticoid receptors may be crucial for peptide regulation in the spinal ganglia. These results may be of relevance to adrenalectomy induced changes in sensory mechanisms, neurogenic inflammation and pain transmission and to a role of substance P and somatostatin in these processes.

Adrenalectomy↗

Thrombospondin and a 140 kd fragment promote adhesion and neurite outgrowth from embryonic central and peripheral neurons and from PC12 cells.

The ability of thrombospondin (TSP), an extracellular matrix glycoprotein, and two proteolytic fragments to support adhesion and neurite outgrowth from embryonic dorsal root ganglia, spinal cord neurons, and PC12 cells was examined. Anti-TSP antibodies or a synthetic peptide (GRGDS) containing an RGD cell-binding region was also added to cells plated on TSP. TSP and its 140 kd fragment were more efficient than laminin controls in supporting adhesion. Neurites formed on laminin, on varying concentrations of TSP, and particularly the 140 kd fragment. The amino-terminal heparin-binding domain supported little adhesion and outgrowth. Both adhesion and process outgrowth on TSP were inhibited by addition of anti-TSP antibodies, but not GRGDS.

Adrenal Gland Neoplasms↗

Endothelin as a putative sensory neuropeptide in the guinea-pig: different properties in comparison with calcitonin gene-related peptide.

Both endothelin-(ET) and calcitonin gene-related peptide- (CGRP) like immunoreactivity (-LI) were present in a variety of organs and neuronal tissue of the guinea-pig as determined by radioimmunoassay (RIA). Neuronal tissues like dorsal root ganglia (DRG) contained by far the highest levels of both ET- (65 +/- 11 pmol/g) and CGRP-LI (34 +/- 5 pmol/g). The tissue levels of ET-LI remained unchanged after 6-hydroxydopamine and capsaicin-pretreatment, while CGRP-LI was markedly reduced after capsaicin. Chromatographic characterization revealed that the main portion of ET-LI in the DRG, right atrium and lung corresponded to synthetic ET-1. Immunohistochemical studies showed the presence of ET-LI in a few neurons of intact DRG and many neurons in DRG cell-cultures, partly co-existing with CGRP-LI. In the neuronal cells of DRG cultures the ratio between the ET- and CGRP-LI was 1:27 compared to 2:1 in intact DRG. 24 h after ligation of the sciatic or vagal nerves no accumulation of ET-LI was observed above the ligation, while CGRP-LI was increased 4-5-fold. Transection (10 days) of the sciatic nerve caused a 85-95% depletion of CGRP-LI in the distal skin, gastrocnemius muscle and trunk below the transection site, while in the proximal portion of the nerve CGRP-LI increased. No effects on ET-LI in these tissues were observed after sciatic nerve transfection. In release experiments on DRG cell cultures. Langendorff heart preparations or perfused guinea-pig lungs, potassium (60 mM), capsaicin or antidromic nerve stimulation evoked a clear-cut increase in the supernatant levels of CGRP-LI, suggesting release, while no effect on the ET-LI concentration was observed in the effluent. Furthermore, anoxia failed to influence the outflow of ET-LI from the heart and lung. It is concluded that ET-1-LI is present in high levels in spinal ganglia and ET-LI occurs in afferent cell-bodies, but in comparison with CGRP, ET shows remarkable inertness upon various experimental conditions including no evidence for axonal transport, loss after denervation or release. The neuronal ET-LI seems to increase under culture conditions, however. The possible function for the high content of ET-LI in the intact guinea-pig peripheral nervous system remains to be elucidated and may mainly be related to a non-neuronal pool considering the relatively low content of ET-LI compared to CGRP in cultured DRG cells.

Animals↗

Real-time imaging of neurons retrogradely and anterogradely labelled with calcium-sensitive dyes.

Membrane-impermeant calcium indicator dyes were used to retrogradely label dorsal root ganglia, spinal motoneurons and interneurons in the spinal cord of the chick embryo. The dyes were also used to label anterogradely primary afferent axons in the spinal cord and synaptic endings in the ciliary ganglion. Labelled neurons were imaged using digital videomicroscopy. Motoneurons and dorsal root ganglion cells exhibited a frequency-dependent change in fluorescence during antidromic stimulation. Single antidromic stimuli resulted in fluorescence transients that could be resolved in individual cells in real time. In addition, fluorescence changes could be recorded in motoneurons during episodes of bursting generated by rhythmic synaptic inputs from premotor networks. Stimulus-induced fluorescence signals were also detected in axons and synaptic endings labelled anterogradely. Optical signals were largely abolished in the absence of extracellular calcium. The results show that calcium changes can now be measured in identified populations of neurons and presynaptic terminals. The strong dependence of these signals on impulse activity suggests that the technique will be useful for monitoring the activity of identified neuronal populations. The calcium-dependent fluorescence signal probably results from cytosolic dye derived from diffusion which may limit the technique to situations in which the dye can be applied close (< 1 cm) to cell bodies.

Animals↗

Schwann cells are not required for guidance of motor nerves in the hindlimb in Splotch mutant mouse embryos.

The topogenesis of the hindlimb nerves of Splotch homozygous mutant mouse embryos was studied using light and electron microscopy. Homozygous mutants show multiple defects of neural crest-derived tissues. The defects increase along a rostro-caudal gradient. The cervical and upper thoracic segments have small spinal ganglia, and Schwann cells are associated with the spinal nerves. In the lumbo-sacral region neurulation is not complete, and the derivatives of the neural crest are missing. The lumbo-sacral nerve trunks are formed by ventral roots only. They are occasionally associated with presumptive glial cells that have migrated from the spinal cord for a short distance. Beyond the vertebral primordia, the spinal nerves are not accompanied by Schwann cells. No compartmentalization of the axons within the lumbo-sacral nerves was visible, whereas Schwann cells did segment the nerve into the fascicles in brachial nerves. The lumbo-sacral plexus develops, and its branches grow into the hindlimb despite the absence of Schwann cells. On day 13.5 of gestation, the lumbo-sacral nerve trunks extend well into the distal calf. They are topographically correctly positioned. Their branches enter the muscle primordia and form contacts with their mesenchymal cells though the cutaneous branches are missing. Generally, the outgrowth of lumbo-sacral nerves is slower than in phenotypically normal littermates, whose nerves reach the foot plate at corresponding stages of development. These results demonstrate that the lumbo-sacral plexus and the topographically correct position of lumbo-sacral nerve trunks develop despite the absence of Schwann cells. Therefore Schwann cells are not necessary for the outgrowth and guidance of axons within the limb.

Animals↗

Morphometric evaluation of degenerative and regenerative changes in isoniazid-induced neuropathy.

Morphometric studies of the pathologic changes were carried out on the peripheral nerves, spinal roots, and different levels of the Goll's tract in rats given isoniazid and killed 1, 2, 3, 4, 5, 6, 7, 14, and 30 days after intoxication. In teased fiber preparations, axonal degeneration was the main change present, and this was seen as early as day 2 in the peroneal and distal sural nerves. The frequency of myelinated fibers showing axonal degeneration was higher in the distal than the proximal sural nerve, and in the ventral than the dorsal root. In the group of rats killed on 5, 6, 7, and 14 days, a significant decrease of the myelinated fiber density was observed in the distal and proximal sural nerves, ventral root, and at the third cervical level of the Goll's tract. The degree of fiber degeneration was more severe in the distal than in the proximal sural nerve and in the third cervical than the fifth thoracic level of the Goll's tract. Preferential decrease of large myelinated fibers was noted in all the affected nerves. No definite abnormalities, however, were seen in nerve cells of the 6th lumbar spinal ganglia and anterior horn cells of the lumbar spinal cord on light microscopy. On 30 days, regeneration at varying degrees was discerned in all the affected nerves with significant increase of small myelinated fibers, particularly in the ventral root. The findings indicate that both centrally and peripherally directed myelinated axons are more affected in the distal than in the proximal segments while the neuronal cell bodies are spared. The spatio-temporal evolution of this pattern of change is compatible with the concept of the "dying back" process or central-peripheral distal axonopathy.

Animals↗

Primary afferent neurons intrinsic to the guinea-pig intestine, like primary afferent neurons of spinal and cranial sensory ganglia, bind the lectin, IB4.

The plant lectin, IB4, binds to the surfaces of primary afferent neurons of the dorsal root and trigeminal ganglia and is documented to be selective for nociceptive neurons. Physiological data suggest that the intrinsic primary afferent neurons within the intestine are also nociceptors. In this study, we have compared IB4 binding to each of these neuron types in the guinea-pig. The only neurons in the intestine to be readily revealed by IB4 binding have Dogiel-type-II morphology; these neurons have been previously identified as intrinsic primary afferent neurons. Most of the neurons that are IB4-positive in the myenteric plexus are calbindin-immunoreactive, whereas those in the submucosal ganglia are immunoreactive for NeuN. The neurons that bind IB4 strongly have a similar appearance in enteric, dorsal root and trigeminal ganglia. Binding is to the cell surface, to the first part of axons and to cytoplasmic organelles. A low level of binding was found in the extracellular matrix. A few other neurons in all ganglia exhibit faint staining with IB4. Strongly reactive neurons are absent from the gastric corpus. Thus, IB4 binding reveals primary afferent neurons with similar morphologies, patterns of binding and physiological roles in enteric, dorsal root and trigeminal ganglia.

Animals↗

Ottorino Rossi and the medical tradition of Pavia.

Ottorino Rossi was a remarkable Italian neurologist of the first half of this century. He made important contributions to many fields of clinical neurology, neurophysiopathology and neuroanatomy. Among these are: the identification of glucose as the reducing agent of the cerebrospinal fluid, the demonstration that fibres from the spinal ganglia pass into the dorsal branch of the spinal roots, and the description of the cerebellar symptom which he termed "the primary asymmetries of positions". Moreover, he conducted important studies on the immunopathology of the nervous system, on the serodiagnosis of neurosyphilis and on the regeneration of the nervous system. He studied pathological anatomy under Camillo Golgi and clinical neurology under Casimiro Mondino and completed his clinical preparation in Florence with Eugenio Tanzi, and in Munich at the Institute directed by Emil Kraepelin. Ottorino Rossi taught at the Universities of Siena, Sassari and Pavia; in the last town he was made Dean of the University and managed to have the buildings of the new San Matteo Polyclinic completed. Ottorino Rossi was one of Camillo Golgi's most illustrious pupils as well as one of the most eminent descendants of Pavia's medico-biological tradition.

History, 20th Century↗

Cx36 is dynamically expressed during early development of mouse brain and nervous system.

Connexins are structural proteins that are part of the gap junctional channels which couple cells in different tissues. Connexin36 (Cx36) is a new member of the connexin gene family, found to be expressed essentially if not exclusively in neuronal cells in adult CNS of mouse, rat and man. Here we have studied Cx36 expression during murine embryonic development. Cx36 shows a highly dynamic pattern of expression. It is first (E9.5) evident in the forebrain and later its expression expand caudally in the midbrain. At E12.5 its expression correlates with major morphogenetic boundaries in the developing mouse brain, specifically with the dorsoventral telencephalic boundary and the Zona Limitans Intrathalamica. Starting at midgestation (E12.5), it is also expressed in both sympathetic and spinal ganglia, and in two longitudinal stripes along the spinal cord.

Animals↗