Bcl-2 and neuronal selection during development of the nervous system.
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Cell Death↗
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Results for “GANGLIA, SPINAL”
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[Human peripheral neurolymphomatosis].
Two further cases of human neurolymphomatosis are reported, and clinical, histopathologic and nosologic features of the affection reviewed with respect to findings in these 2 patients and in 7 other reported cases. Clinical manifestations are those of a flaccid ascending paralysis, associated in most cases with an asymmetrical abolition of tendon reflexes, violent muscular pains and sphincter disturbances, frequently preceded by a regressive cranial nerve palsy. Pathology shows infiltration of the peripheral nervous system (nerves, roots, and spinal ganglia) by lymphoid cells, sometimes associated with central nervous system (cord and brain) infiltrates in severe advanced cases. Involved nerves are increased in size. The disease could be a viral polyradiculoneuritis due to the virus of Marek's disease. Arguments in favor of this hypothesis include: the onset of the affection in subjects working in poultry farms under poor hygienic condition; the fact that clinical and histologic findings are similar to those in Marek's disease and the failure, after careful examination, to detect any malignant blood disorder or lymphoma in one of the cases studied.
Adult↗
Conditioned medium from cultures of embryonic neurons contains a high molecular weight factor which induces acetylcholine receptor aggregation on cultured myotubes.
The developmental mechanisms involved in the formation of stable arrays of postsynaptic neurotransmitter receptors near sites of neurotransmitter release are essentially unknown. However, several recent studies have shown that cells or tissues of neural origin produce macromolecular factors which induce an increase in the number of acetylcholine (ACh) receptors or the number of receptor aggregates on cultured embryonic myotubes. We have tested primary cultures of embryonic neurons and other cell types for the release of an ACh receptor aggregation factor. Conditioned medium from the cultures was applied to cultures of embryonic rat myotubes for 1 day; ACh receptors on the myotubes were stained with tetramethylrhodamine-labeled alpha-bungarotoxin and ACh receptor aggregation activity, defined as the change in the number of receptor aggregates per myotube, was assayed. Aggregation activity with a molecular weight greater than or equal to 50,000 was released by cultures of neurons from sympathetic ganglia, dorsal root ganglia, spinal cord, and cerebellum. Little or no activity was released by glial or other non-neuronal cultures. Release of aggregation activity by different neuronal cell types varied by up to an order of magnitude; however, this variation was not well correlated with the differences in ACh synthesis. The factor(s) in neuronal cell conditioned medium induced a rearrangement of pre-existing receptors at the cell surface, and its action was not dependent on new protein synthesis. The results of this study are consistent with the idea that one or more receptor aggregation factors secreted by neurons are involved in the organization of neurotransmitter receptors during synapse formation in vivo.
Animals↗
NGF and IL-1beta are co-localized in the developing nervous system of the frog, Xenopus laevis.
NGF, a neurotrophic factor best known for its role in promoting cell survival, regulates many neurodevelopmental processes, including synaptic plasticity, neurite outgrowth and programmed cell death. Although there is a large amount of data regarding NGF in the developing nervous system of many species, there is little known about its regulation and role in the frog, Xenopus laevis. In this report, immunocytochemistry was used to characterize NGF protein expression in developing tadpoles. Protein expression was analyzed in tadpoles from stage 44/45 through stage 50, a period of development characterized by extensive neurite outgrowth, neuronal differentiation and an initial period of programmed cell death. Similar to other species, NGF was expressed in sensory cells and tissues, including the inner ear, eye, olfactory system, lateral line organs, papillae in the oral cavity, and gills tufts. In addition, NGF was expressed in specific cells in the central nervous system, cranial and dorsal root ganglia, spinal sensory and motoneurons, and muscle tissues in the tail and body cavity. In the mammalian nervous system, the cytokine, interleukin-1beta (IL-1beta) induces expression of NGF. In this report, double-label immunocytochemistry was used to determine the relationship between NGF and IL-1beta. Results showed most cell types and/or tissues that expressed NGF also expressed IL-1beta. However, NGF was typically associated with cellular and nuclear membranes, whereas IL-1beta appeared in the cytoplasm and nucleolus. The nuclear localization of IL-1beta supports the idea that it regulates gene transcription in the frog. The appearance of NGF and IL-1beta in the same cells suggests they may interact to influence neural development.
Animals↗
Adoptive transfer-experimental allergic neuritis in newborn Lewis rats results in inflammatory infiltrates, mast cell activation, and increased Ia expression with only minor nerve fiber degeneration.
Experimental allergic neuritis (EAN) induced in the Lewis rat by the adoptive transfer of a P2-specific T cell line (AT-EAN) is considered an animal model of Guillain-Barré syndrome. It is not yet known whether AT-EAN is inducible at early stages in the development of the peripheral nervous system (PNS) or whether disease activity is modified because of immaturity of either the nervous system or the immune system. We therefore compared the susceptibility of neo-natal and adult Lewis rats to AT-EAN induced by the adoptive transfer (intraperitoneally) of 10(6) activated P2-specific T cells. P2 antigen was already present in 7 day old Lewis rats and P2-specific T cell transfer into 3-day-old rats induced clinical disease associated with an inflammatory response (sciatic nerves and spinal ganglia). In injected newborn rats we observed local activation of mast cells, infiltration of the PNS by inflammatory cells, and induction of Ia antigen expression in Schwann cells. Unlike in adults, segmental or paranodal demyelination despite occasional nerve fiber degeneration did not occur. However, the difference between newborn and adult rats could not be ascertained statistically because of the relative rarity of the lesions, their focal character, the admixture of fiber demyelination and degeneration, and most importantly, size differences of the myelinated fibers, which result in a large developmental decrease in fiber density in adults compared to newborns.
Adoptive Transfer↗
Macroscopical observations on a human anencephalous fetus with multiple malformations (author's transl).
The present report treats a female stillborn human anencephalous fetus with the craniorrhachischisis, cleft palate, left-sided congenital diaphragmatic hernia, hypoplasia of lungs, imperforate vagina and anus, absent left kidney and sternal muscle on the left side. In view of the rarity of the records of autopsied cases of anencephaly, authors made efforts to obtain informations on how all the organs in this fetus and their topographical relation in each other are affected by the anencephaly. The findings are summarized as follows. 1) This case falls under Anencephalus craniorrhachischisis in NANAGAS (1925)'S classification. 2) The greater part of thoracic and lumbar vertebral column except T10, 11, 12 and L1 segments shows several segmental malformations. The lumbar vertebral column is twisted towards right and the left posterior abdominal wall is nearly absent. Due to these changes, only two ribs are present on the left side. 3) In this case, there is a congenital diaphragmatic hernia through persistent left sided pleuroperitoneal canal. The abdominal viscera protruded into the pleural cavity are the caecum, vermiform appendix, colon, spleen and pancreas. 4) On both sides, the ventral rami of the thoracic, lumbar and sacral nerves are normal in number. Their spinal ganglia situated on these nerve roots are, however, fused to form eight ganglionic masses. 5) The five short left thoracic ventral rami arise from a ganglion lying on the posterior thoracic wall. This ganglion gives off the two branches communicating with the right 7th, 8th and 11th thoracic nerves. On the other hand, the right lumbar plexus receives the left 1st, 2nd and 3rd lumbar nerves. In the left pelvic part, there is another ganglion which gives off the two large branches to the right 1st and 2nd sacral nerves. 6) From the findings mentioned above, it is advisable to examine not only the ectodermal structures but also mesodermal ones to promote the studies on a factor in the genesis of anencephaly.
Abdomen↗
Neuronal pp60c-src(+) in the developing chick spinal cord as revealed with anti-hexapeptide antibody.
Polyclonal antibody was raised in rabbits against a synthetic hexapeptide R-K-V-D-V-R corresponding to a unique amino acid sequence of the neuron-specific c-src gene product pp60c-src(+). The antibody was purified by affinity chromatography. A single band with an apparent molecular mass of 60 kDa was recognized when the supernatant of homogenates of brain and spinal cord from chick embryos and chicks was probed with the affinity purified anti-hexapeptide antibody after SDS-polyacrylamide gel electrophoresis followed by Western blotting. Specificity of the antibody was further characterized by autophosphorylation assay of immunoprecipitate in comparison with the monoclonal antibody 327. Immunocytochemical studies by light microscopy revealed that pp60c-src(+) was localized in flake-like aggregates in neuronal cell bodies of the spinal cord in 7-15-day-incubated chick embryos and newly hatched chicks. Developing spinal ganglia and muscle cells were also immunoreactive at early developmental stages. By electron microscopy, the reaction product was observed mainly in two regions. One region was at polysomes and along the membranes of the rough endoplasmic reticulum. The other region was along the neuronal plasma membrane--at subsurface cisterns and at synapses. At synapses, the postsynaptic density, presynaptic membrane and synaptic vesicle membranes were immunostained. Immunoreactivity at synapses were more frequently observed at earlier stages than at later stages of development. These findings suggest that pp60c-src(+) is actively produced in developing neurons and has some important roles in synaptogenesis. In mature synapses, pp60c-src(+) may be involved in the interaction of synaptic vesicles with the presynaptic membrane.
Amino Acid Sequence↗
Neck injuries in car collisions--a review covering a possible injury mechanism and the development of a new rear-impact dummy.
A review of a few Swedish research projects on soft tissue neck injuries in car collisions is presented together with some new results. Efforts to determine neck injury mechanisms was based on a hypothesis stating that injuries to the nerve root region in the cervical spine are a result of transient pressure gradients in the spinal canal during rapid neck bending. In experimental neck trauma research on animals, pressure gradients were observed and indications of nerve cell membrane dysfunction were found in the cervical spinal ganglia. The experiments covered neck extension, flexion and lateral bending. A theoretical model in which fluid flow was predicted to cause the transient pressure gradients was developed and a neck injury criterion based on Navier-Stokes Equations was applied on the flow model. The theory behind the Neck Injury Criterion indicates that the neck injury occurs early on in the rearward motion of the head relative to the torso in a rear-end collision. Thus the relative horizontal acceleration and velocity between the head and the torso should be restricted during the early head-neck motion to avoid neck injury. A Bio-fidelic Rear Impact Dummy (BioRID) was developed in several steps and validated against volunteer test results. The new dummy was partly based on the Hybrid III dummy. It had a new articulated spine with curvature and range of motion resembling that of a human being. A new crash dummy and a neck injury criterion will be very important components in a future rear-impact crash test procedure.
Accidents, Traffic↗
Activity of spinal interneurons and their effects on forearm muscles during voluntary wrist movements in the monkey.
We studied the activity of 577 neurons in the C6-T1 spinal cord of three awake macaque monkeys while they generated visually guided, isometric flexion/extension torques about the wrist. Spike-triggered averaging of electromyographic activity (EMG) identified the units' correlational linkages with </=12 forearm muscles. One hundred interneurons produced changes in the level of average postspike EMG with onset latencies consistent with mono- or oligosynaptic connections to motoneurons; these were classified as premotor interneurons (PreM-INs). Most PreM-INs (82%) produced postspike facilitations in forearm muscles. Earlier spike-related features, often beginning before the trigger spike, were seen in spike-triggered averages from 72 neurons. Postspike effects were present in one muscle for 64% of the PreM-INs. Neurons with divergent linkages to larger "muscle fields" usually generated postspike effects in synergistic muscles. Fifty-eight percent of the PreM-INs had postspike effects in flexor muscles only and 29% in extensor muscles only. Postspike effects were distributed relatively evenly among the primary flexor and extensor muscles studied. The mean percent change in EMG level from baseline and the mean onset latencies for postspike facilitations and postspike suppressions were similar. PreM-INs exhibited a variety of response patterns during the generation of isometric wrist torque. The response patterns and output effects of 24% of the PreM-INs were consistent with a strict reciprocal organization of flexor and extensor muscle control. For another 60% of the PreM-INs, there was a congruent relation between activity and output effects for only one direction of torque production. These neurons were active for both flexion and extension torques, including 37 neurons that exhibited bidirectional increases in discharge rate. The relatively small number of postspike suppressions observed suggests that inhibitory interneurons were silent when their target muscles were recruited. Compared with premotor neurons in the motor cortex, the red nucleus and the C8-T1 dorsal root ganglia, spinal PreM-INs affected flexor muscles in greater proportions and had smaller muscle fields. The magnitudes of postspike facilitations were similar in all premotor populations. Bidirectional activity, common for PreM-INs, was rare for corticomotoneuronal and premotor dorsal root ganglion cells, which discharge only for torques in their preferred direction.
Action Potentials↗
Ontogeny of dopaminergic D-2 receptors in the rat nervous system: characterization and detailed autoradiographic mapping with [125I]iodosulpride.
[125I]Iodosulpride, a highly selective and sensitive probe for dopamine D-2 receptors, was used to study the expression of these receptors in binding studies performed on membranes and serial autoradiographic sections, throughout pre- and postnatal developmental periods. D-2 receptors were first detected autoradiographically in sensory and sympathetic ganglia at the embryonic age of 12 days, i.e. much earlier than in previous studies. In membrane binding studies, D-2 receptors were found to be modulated by guanylnucleotides as early as at embryonic day 15, suggesting that they were already functionally coupled to a regulatory G protein. The overall development of D-2 receptors in the central nervous system occurred according to a caudorostral gradient and was accompanied by a slightly but significantly increased affinity for dopamine, possibly related to the late expression of a D-2 receptor subclass. The ontogeny of D-2 receptors was compared to that of tyrosine hydroxylase immunoreactivity as reported by others and taken as an index of dopaminergic innervation. Despite some variations due to experimental conditions, this comparison resulted in the definition of various situations. In some major projection areas (e.g. caudate putamen at embryonic day 14) there was a simultaneous appearance of both dopaminergic markers whereas in most others (e.g. n. accumbens or olfactory tubercles at embryonic day 20) the appearance of D-2 receptors was preceded by 1-4 days by that of tyrosine hydroxylase immunoreactivity. However, in a few projection areas (e.g. the bed nucleus of the stria terminalis at embryonic day 21), D-2 receptors appeared 3-4 days earlier than tyrosine hydroxylase immunoreactivity. In areas of dopaminergic perikarya, e.g. substantia nigra and ventral tegmental area, where they largely correspond to somatodendritic autoreceptors, D-2 receptors appeared at embryonic days 17 and 21 respectively, i.e. 3-8 days after tyrosine hydroxylase immunoreactivity, suggesting that dopamine synthesis and release is not feedback regulated by autoreceptors at initial developmental stages. In areas where D-2 receptors are present in the absence of any established dopaminergic innervation (e.g. discrete layers of the hippocampus, cerebellum, parietal cortex or in cranial nerve nuclei), they generally appeared at a late stage, i.e. during the second or even the third postnatal week. Finally, there was transient and roughly concomitant expression of both D-2 receptors and tyrosine hydroxylase immunoreactivity in some areas such as spinal ganglia or the lateral ventricle floor, consistent with a possible development function of dopamine mediated by D-2 receptors.
Aging↗
Abnormalities of neural tube formation in pre-spina bifida splotch-delayed mouse embryos.
The splotch-delayed homozygous mutant (Spd/Spd) develops spina bifida with or without exencephaly, has spinal ganglia abnormalities, and delays in posterior neuropore closure and neural crest cell emigration. The heterozygote (Spd/+) has a pigmentation defect, and occasionally neural tube defects. To investigate the underlying mechanisms, we compared the neuroepithelium in the posterior neuropore region of cytogenetically identified 15-18 somite pair Spd/Spd, Spd/+, and +/+ mouse embryos by transmission electron and light microscopy. The notochordal area and cell number in the non-fused neuroepithelium region of Spd/Spd and Spd/+ embryos were significantly reduced compared to those of normal (+/+) embryos, which suggests an abnormality in notochord elongation. In the mesoderm, the mean cell number and mean ratio of cell number to area in the non-fused region were significantly lower in the Spd/Spd compared with +/+ embryos. The distance of exposed neuroepithelium above the mesoderm in the just-fused region was significantly lower in the Spd/Spd versus +/+ embryos, which may indicate an insufficient force exerted by the mesoderm during neural tube closure. Within the neuroepithelium, significantly more intercellular space was found in Spd/Spd than in +/+ embryos indicating disorganization. The basal lamina was poorly organized and the formation delayed around the neural tube in Spd/Spd and Spd/+ embryos. All together, these results suggest an early abnormality in interactions among the neuroepithelium, mesoderm, and notochord, which may lead to the delay or inhibition of neural tube closure observed in Spd/Spd mutants.
Animals↗
System to identify individual somites and their derivatives in the developing mouse embryo.
The identification of the axial levels of metameric elements along the rostro-caudal axis of vertebrates until now was not possible before late, fetal development, when the vertebral anlagen first appear. We developed a new system for the exact axial identification of somites and their derivatives from early, embryonic stages of mouse development on (Theiler stages (TS) 15 to TS18-19). The initial axial identification of the somites was performed by relating them to the rostral-most two cervical spinal ganglia (SG), that exhibited characteristic morphologies (SG-C1: bar-like, SG-C2: triangular). At all stages of somitic development, the most prominent somite along the rostro-caudal axis correlated with the bar-like SG-C1, and, therefore, we named it the first cervical somite (SO-C1). The next step, the axial identification of the somites independently from the SG, was based on the observation that after in situ hybridization to Myf5, Pax3, Pax1, and Mox1 riboprobes, a distinct and characteristic morphology of the last occipital somite (SO-O5) and the first two cervical somites (SO-C1, SO-C2) can be observed. From TS15 on, these three somites formed a triad of the most prominent somites along the rostro-caudal axis. Also, the dermomyotomal, myotomal, and sclerotomal derivatives of this somite triad were the most prominent in later somitic development. Furthermore, SG-C1 and SG-C2 exhibited a transient bipartite anlagen in their early development, suggesting a "resegmentation" during SG formation. Later, when somites started to dissolve, the caudal moiety of the bar-like SG-C1 anlagen fused to the anlagen of SG-C2.
Alcohol Oxidoreductases↗
Nerve growth factor-stimulated mitogen-activated protein kinase activity is not necessary for neurite outgrowth of chick dorsal root ganglion sensory and sympathetic neurons.
Nerve growth factor (NGF)-stimulated neurite outgrowth in the rat PC12 tumor cell line recently has been shown to depend on the activation of the mitogen-activated protein (MAP) kinase kinase 1 (MEK1) (Pang et al.: J Biol Chem 270:13585-13588, 1995). In this study we have analyzed whether or not function of the MAP kinase pathway is necessary for NGF-stimulated neurite outgrowth in two subtypes of primary neurons derived from the embryonic chick peripheral nervous system (PNS). Treatment of p21ras-dependent dorsal root ganglion (DRG) sensory neurons (E9) with the MEK1 inhibitor PD98059 at concentrations up to 100 microM did not prevent NGF-stimulated neurite outgrowth. At this concentration NGF-stimulated tyrosine phosphorylation of MAP kinase p42 as well as MAP kinase activity both were decreased by approximately 80%. Essentially the same results were obtained with p21ras-independent sympathetic neurons (E12). We conclude that, in contrast to the PC12 tumor cell line, NGF-stimulated MAP kinase activity is not necessary for neurite outgrowth of DRG sensory and sympathetic neurons derived from the chick PNS.
Animals↗
Bifunctional fusion between nerve growth factor and a transferrin receptor antibody.
The cDNAs encoding the variable regions of the heavy and light chains of a murine antibody specific for the human TfR were cloned and a human chimera (gamma1, kappa) was produced. A gene fusion was created by joining the 3' end of the coding region of the human nerve growth factor (NGF) precursor to the 5' end of the heavy chain variable region of the chimeric antibody. When expressed with the unmodified light chain in mammalian cells, the protein fusion is properly processed, assembled, and secreted. Subsequent purification and characterization established the uncompromised bifunctional activities of the protein, relative to the unmodified components, as demonstrated by its ability to both bind to the human TfR and induce neurite outgrowth in primary sympathetic or spinal ganglia and in trkA-transfected pheochromocytoma cells. The ability to generate biologically active NGF fused to a TfR targeting antibody, which was previously shown to cross the blood-brain barrier, may offer a novel way to deliver NGF and other neurotrophic factors to the central nervous system.
Animals↗
Two Nkx-3-related genes are expressed in the adult and regenerating central nervous system of the urodele Pleurodeles waltl.
We report the isolation and characterization of two NK-3-related genes (PwNkx-3.2 and PwNkx-3.3) and their expression patterns during embryonic development, in the adult CNS, and during tail regeneration in the urodele Pleurodeles waltl. PwNkx-3.2 is the ortholog of the mouse and Xenopus genes, Bapx 1 and Xbap, but PwNkx-3.3 has no known homologue in any other vertebrate. We demonstrate that PwNkx-3.2 and PwNkx-3.3 exhibit graded axial expression patterns in adult spinal cord. During tail regeneration, the two genes are expressed in the wound epidermis, the regenerating muscle masses, the regenerating neural tube, the spinal ganglia, and the cartilage rod. The spatial distribution of transcripts in the CNS suggests that these genes could participate in maintaining the position information along the anteroposterior axis and may explain the ability of the adult CNS to regenerate. During tail regeneration, both genes could be implicated in the reformation of the axial skeleton.
Amino Acid Sequence↗
Urinary retention due to herpes virus infections.
Urinary retention is uncommon in patients with herpes zoster and anogenital herpes simplex. Seven patients (four men, three women) with a mean age of 68.1 years (range, 35-84) with urinary retention due to herpes zoster (n = 6) or anogenital herpes simplex (n = 1) were studied. Six patients had unilateral skin eruption in the saddle area (S2-4 dermatome) and one patient with herpes zoster had a skin lesion in the L4-5 dermatome. All patients had detrusor areflexia without bladder sensation, and two of them had inactive external sphincter on electromyography at presentation. Clean intermittent catheterization was performed, and voiding function was recovered in 4-6 weeks (average, 5.4) in all patients. Urodynamic study was repeated after recovery of micturition in three patients, and they returned to normal on cystometrography and external sphincter electromyography. Acute urinary retention associated with anogenital herpes infection has been thought to occur when the meninges or sacral spinal ganglia were involved, and, in conclusion, this condition may be considered to be reversible.
Acyclovir↗
Dissociated dorsal root ganglia in tissue culture.
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Ganglia↗
Antibodies to cerebellar Purkinje cells in patients with paraneoplastic cerebellar degeneration and ovarian carcinoma.
Sera from 2 patients with ovarian carcinoma and paraneoplastic cerebellar degeneration confirmed postmortem were reacted with frozen sections of human cerebellum and stained using indirect immunofluorescence methods. Both sera produced bright cytoplasmic staining of Purkinje cells and of neurons within deep cerebellar nuclei. Titration of these sera to end point revealed staining at final dilutions of 1:640 and 1:2,560, respectively. Neither of these sera reacted with sections of human cerebrum, basal ganglia, spinal cord, peripheral nerve, lung, liver, kidney, or ovary. Staining of Purkinje cells was not obtained with sera from 34 normal, healthy controls, 5 patients with oat cell carcinoma of the lung, 6 patients with inflammatory central nervous system disorders, or 12 of 14 neurologically normal patients with ovarian carcinoma. Sera from 2 neurologically normal patients with ovarian carcinoma, however, produced staining of Purkinje cells and deep nuclei similar to that obtained with sera from patients with paraneoplastic cerebellar degeneration. The present study documents the presence of antibodies to Purkinje cells in patients with ovarian carcinoma and cerebellar degeneration and demonstrates that development of these antibodies may antedate the onset of clinically evident cerebellar degeneration.
Antibodies↗