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W D Snider

Publications and source records attributed to W D Snider.

At least 73 records · Page 4Linked to original sources
PubMed1992

Dorsal root ganglion neurons expressing trk are selectively sensitive to NGF deprivation in utero.

In utero immune deprivation of the neurotrophic molecule nerve growth factor (NGF) results in the death of most, but not all, mammalian dorsal root ganglion (DRG) neurons. The recent identification of trk, trkB, and trkC as the putative high affinity receptors for NGF, brain-derived neurotrophic factor, and neurotrophin-3, respectively, has allowed an examination of whether their expression by DRG neurons correlates with differential sensitivity to immune deprivation of NGF. In situ hybridization demonstrates that virtually all neurons expressing trk are lost during in utero NGF deprivation. Most, if not all, neurons expressing trkB and trkC survive this treatment. In contrast, the low affinity NGF receptor, p75NGFR, is expressed in both NGF deprivation-resistant and -sensitive neurons. These experiments show that DRG neurons expressing trk require NGF for survival. Furthermore, at least some of the DRG neurons that do not require NGF express the high affinity receptor for another neurotrophin. Finally, these experiments provide evidence that trk, and not p75NGFR, is the primary effector of NGF action in vivo.

Animals↗
PubMed1992

Selective dependence of mammalian dorsal root ganglion neurons on nerve growth factor during embryonic development.

We have investigated the NGF dependence of dorsal root ganglion (DRG) neurons in mammals using a paradigm of multiple in utero injections of a high titer anti-NGF antiserum. We have determined the specificity of our antiserum in relation to other members of the NGF neurotrophin family and found no cross-reactivity with brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3). To identify various classes of DRG neurons, we have stained their characteristic central projections with Dil. We show here that the NGF dependence of DRG neurons is strikingly selective. Although a majority of DRG neurons are lost after NGF deprivation during embryonic life, these are almost exclusively small diameter neurons that project to laminae I and II of the dorsal horn and presumably subserve nociception and thermoreception. Larger neurons that project to more ventral spinal laminae and subserve other sensory modalities do not require NGF for survival. These NGF-independent DRG neurons likely require one of the more recently identified neurotrophins, BDNF or NT-3.

Afferent Pathways↗
PubMed1992

Interactions between dorsal root axons and their target motor neurons in developing mammalian spinal cord.

We have utilized the lipid-soluble tracers Dil and DiA to investigate interactions between group la dorsal root afferent axons and their target motor neurons in developing rat spinal cord. We show here that la axons project toward motor pools in fascicles that exhibit a considerable degree of spatial order. A rough topography is present in that axons that innervate medially located axial motor neurons cross over others in the intermediate zone and follow a separate path along the midline toward their appropriate targets. Surprisingly, we have also found that motor neuron dendritic projections are well established in the transverse plane prior to the arrival of la afferents. Although dendrites from motor pools innervating limb muscles project directly in the path of incoming la afferents, they do not guide afferents to appropriate motor pools. The la afferents pass over the distal dendrites and grow all the way to the border between gray and developing white matter. A significant amount of terminal branching and bouton formation is in the vicinity of motor neuron somata and proximal regions of the dendritic arbors. Few boutons are found near dendrites that project dorsal to the motor pools, and virtually no boutons are found on dendrites in white matter. Our results show that la afferent axons are not guided to appropriate motor pools by random encounters with motor dendrites, and raise the possibility that mechanisms exist that promote an orderly projection of la afferents to particular regions of the ventral horn. The striking lack of innervation of white matter and dorsally directed dendrites by la afferents raises the question of whether descending and intersegmental systems have their initial interactions with these regions of the motor neuron dendritic arbor.

Animals↗
PubMed1991

Administration or deprivation of nerve growth factor during development permanently alters neuronal geometry.

We investigated whether the administration or deprivation of a neuronal growth factor during development can permanently alter the dendritic architecture of sensitive neurons. Nerve growth factor (NGF) or NGF antiserum treatment in the first 2-3 postnatal weeks markedly affected the survival, size, and dendritic arborization of mouse sympathetic ganglion cells acutely. Six months after the completion of treatment, the number of surviving neurons, cell body size, and higher order dendritic branching had changed considerably from their values at 3 weeks, suggesting that these parameters remain malleable throughout postnatal life. However, the number of primary dendrites, a fundamental determinant of organization within sympathetic ganglia, was permanently altered by the neonatal treatment protocol. The idea emerging from this study is that NGF influences the elaboration of primary dendrites by sympathetic ganglion cells only during a critical developmental period. In maturity, NGF acts as a "maintenance" factor necessary for normal neuronal function and survival, but neurons lose the capacity to respond with wholesale rearrangements of dendritic architecture.

Animals↗
PubMed1991

PDGF A-chain gene is expressed by mammalian neurons during development and in maturity.

Platelet-derived growth factor (PDGF) may be a critical factor in the temporal differentiation of glial elements in the mammalian central nervous system. We have used in situ hybridization and immunoperoxidase staining to investigate the localization of PDGF A and have observed high levels of PDGF A-chain mRNA and immunoreactive PDGF A in neurons of embryonic and adult mice. PDGF A-chain expression was shown to be developmentally regulated and tissue specific. Every neuronal population examined in the central and peripheral nervous systems expresses PDGF A transcripts. Variable, significantly weaker signals are observed in glial cells. In contrast to known neurotrophic factors, the PDGF A transcripts are widely distributed among neurons. This generalized distribution of PDGF A transcripts, together with the known effects of PDGF on glial cells in vitro, suggests a unique role of neurons in regulating the proliferation and differentiation of glial cells in vivo.

Animals↗
PubMed1991

Excitotoxicity in the embryonic chick spinal cord.

Recent evidence implicates excitatory amino acids (EAAs), acting as excitotoxic agents, in the pathogenesis of neurological disorders involving the spinal cord. In this study, we used the chick embryo spinal cord as an in vitro model for studying the sensitivity of spinal neurons to the excitotoxic effects of EAA agonists. Compounds tested include the prototypic receptor-specific agonists, N-methyl-D-aspartate (NMDA), quisqualic acid (Quis), and kainic acid (KA), and the plant-derived excitotoxic food poisons, beta-N-oxalylamino-L-alanine, beta-N-methylamino-L-alanine, and domoic acid. Each agonist induced concentration-dependent acute degeneration of neurons distributed throughout the spinal cord. These cytopathological changes consisted of acute edematous degeneration of dendrosomal structures in the dorsal horn and intermediate zone, and dark cell changes with intracytoplasmic vacuolization of motor neurons; this damage is identical to that induced by excitotoxin agonists in other regions of the central nervous system. The NMDA receptor-specific antagonist MK-801 completely blocked toxicity of NMDA, and the nonNMDA antagonist CNQX preferentially blocked the toxicity of Quis- and KA-type agonists in the spinal cord. Our findings suggest that (1) the majority of spinal neurons have all three subtypes of EAA receptors, making them acutely vulnerable to excitotoxin exposure; and (2) EAA antagonists are effective in preventing excitotoxin-induced damage of the spinal cord.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1990

Early axon and dendritic outgrowth of spinal accessory motor neurons studied with DiI in fixed tissues.

We have utilized lateral diffusion of DiI in fixed tissues (Godement et al., '87: Development 101: 697-713) to study early axon and dendritic outgrowth of spinal accessory motor neurons in embryonic rats. Crystals were placed in the central canal of the cervical spinal cord near the ventral commissure in order to label growing accessory axons anterogradely and on the spinal accessory nerve to label somata and dendrites retrogradely. Animals were studied on E11-E13. We show here that it is possible to stain axonal and dendritic processes from the earliest stages of motor neuron differentiation by using DiI. Our results demonstrate that, unlike axons of other cervical motor neurons, accessory axons traverse the lateral region of the embryonic cord, which consists of neuroepithelial endfeet. Thus an affinity for neuroepithelial endfeet could partially explain their unusual intraspinal trajectory. We also show that morphology of the spinal accessory growth cones differs according to position along the accessory nerve pathway. Finally, we show that accessory motor neuron axons are in the region of their target precursors prior to the initiation of dendritic arborization. Use of DiI in fixed tissue allows study of process outgrowth in mammalian spinal cord with detail previously obtainable only in nonmammalian vertebrates.

Animals↗
PubMed1990

Nerve growth factor regulates sympathetic ganglion cell morphology and survival in the adult mouse.

We have investigated the effects of prolonged systemic injections of nerve growth factor (NGF) and its antiserum on the survival and morphology of sympathetic ganglion cells in adult mice. Using intracellular injections of Lucifer yellow in lightly fixed superior cervical ganglia, we show that total dendritic lengths of ganglion cells are increased 29% after 2 weeks of NGF treatment. The increased dendritic length is characterized by increased branching within the dendritic arborization and not by the addition of new primary dendrites. In addition, cell soma cross-sectional area was increased 45%. Conversely, administration of NGF antiserum for 1 month decreased total dendritic length by 33%, decreased ganglion cell body size by 26%, and reduced the number of neurons in the ganglion by 25%. After 3 months of NGF antiserum treatment, the number of neurons in the ganglion was reduced a total of 41%. NGF antiserum treatment for 1 month in aged (22 months old) animals reduced ganglion cell body size by 21% and cell number by 22%, decreases that are comparable to those observed in young adult animals. Our results indicate that, even in maturity, sympathetic ganglion cells remain dependent on NGF for survival and maintenance of dendritic geometry, and this dependence continues into old age.

Animals↗
PubMed1989

Target dependence of hypoglossal motor neurons during development in maturity.

We have investigated the target dependence of hypoglossal motor neurons in postnatal rats by transecting the hypoglossal nerve and preventing reinnervation of the tongue. After transection in early postnatal life, approximately 60% of hypoglossal motor neurons die and surviving neurons are markedly atrophic compared to contralateral controls. In maturity, there is also substantial neuronal atrophy and about 30% of motor neurons appear to die after the procedure. However, most hypoglossal neurons in adults survive transection for periods up to 1 year. The adult response is present by 3 weeks of age. The time course of neuronal atrophy and death after permanent target deprivation was investigated in adult animals. One month after the hypoglossal nerve was deflected, there was marked axonal atrophy, although somatic atrophy was minimal. By 3 months after the procedure substantial neuronal atrophy and apparent cell loss (about 30%) had occurred. There was little change between 3 and 6 months. We conclude that hypoglossal motor neurons are influenced by connections with their targets in postnatal life. Even in maturity, neurons require target connections for maintenance of axonal and somatic morphology. However, the majority of motor neurons in adult animals can survive target deprivation for prolonged periods.

Aging↗
PubMed1989

Neurotrophic molecules.

Neurotrophic molecules have a profound influence on developmental events such as naturally occurring cell death, differentiation, and process outgrowth. Despite their striking effects on developing neurons, a role for these molecules in the pathogenesis or therapy of neurological disease has not yet been defined. However, a variety of recent advances promise to provide the techniques necessary to assess the potential relevance of neurotrophic molecules to clinical neurology. In this article we review recent investigations into the biological effects, regulation of production, and mechanisms of action of the best characterized trophic molecule, nerve growth factor. In addition we review studies characterizing brain-derived neurotrophic factor and other putative neurotrophic molecules. Finally, we discuss how pharmacological effects of these molecules may be relevant to the therapy of disease states as well as neural regeneration.

Animals↗
PubMed1988

Trophic regulation of nerve cell morphology and innervation in the autonomic nervous system.

A remarkable feature of nerve cells is the complex and variable pattern of their axonal and dendritic branches. Quantitative studies of a simple part of the nervous system in mammals provide evidence that neuronal geometry and innervation are regulated by long-term trophic interactions between neurons and their targets. This trophic linkage may explain how nerve cells adjust their function to the needs of bodies that vary markedly in size and form.

Autonomic Nervous System↗
PubMed1988

Retrograde transport of nerve growth factor (NGF) in motoneurons of developing rats: assessment of potential neurotrophic effects.

The potential functional significance of nerve growth factor (NGF) receptors in spinal motoneurons was studied in newborn rats. 125I-NGF was specifically retrogradely transported by motoneurons from their peripheral nerve terminals. This transport was blocked by an excess of unlabeled NGF but not by cytochrome c. 125I-cytochrome c was not transported. The monoclonal anti-rat NGF receptor antibody, but not a control antibody, was also transported. Despite this ability of motoneurons to transport NGF, treatment of newborn rats with this factor did not increase motoneuron size or synthesis of neurotransmitter enzymes and did not prevent cell death after axotomy. We conclude that NGF receptors of spinal motoneurons can bind, internalize, and retrogradely transport NGF. However, these receptors do not mediate the classic trophic effects of NGF.

Animals↗
PubMed1988

Nerve growth factor enhances dendritic arborization of sympathetic ganglion cells in developing mammals.

Recent observations have suggested that the dendritic arbors of sympathetic ganglion cells may be regulated by interactions with their peripheral targets (Voyvodic, 1987a; Yawo, 1987). In order to assess a potential mechanism for such interactions, I have investigated the effects of the target-derived trophic molecule for sympathetic ganglion cells on the development of dendrites in the rat superior cervical ganglion. Systemic treatment of neonatal animals with NGF for 1 or 2 weeks results in a striking expansion of ganglion cell dendritic arbors, as revealed by intracellular staining with HRP. During this period, neurons in treated animals extend new primary dendrites, and the length and branching of existing dendrites are increased compared to age-matched controls. These results support the idea that targets may regulate ganglion cell arbors via elaboration of NGF, and suggest an explanation for the correlation between animal size and dendritic complexity noted in several recent studies (Purves and Lichtman, 1985a; Snider, 1987; Voyvodic, 1987a).

Animals↗
PubMed1987

The dendritic complexity and innervation of submandibular neurons in five species of mammals.

I have compared the dendritic complexity and innervation of homologous parasympathetic ganglion cells in several closely related species of mammals. In the smaller of these species (mouse, hamster, and rat), submandibular ganglion cells generally lack dendrites altogether and are innervated by a single axon. In the guinea pig, a somewhat larger species, these neurons possess rudimentary dendritic arbors and are innervated by 2 axons, on average. In the largest species investigated, the rabbit, submandibular ganglion cells have moderately complex dendritic arbors and receive innervation from several axons. These findings, together with a previous study of sympathetic ganglion cells in these same species (Purves and Lichtman, 1985a), indicate that relationships among neuronal morphology, convergent innervation, and animal size are widespread in the autonomic nervous system of mammals.

Animals↗
PubMed1986

Rostrocaudal differences in dendritic growth and synaptogenesis in rat sympathetic chain ganglia.

Vertebrate embryos show a rostral to caudal gradient of morphogenesis. I have investigated the effect of this developmental gradient on neuronal maturation and synapse formation by comparing the development of rostral and caudal sympathetic chain ganglia in the rat. In young adults the superior cervical and lumbar ganglia are almost identical in terms of neuronal morphology and quantitative aspects of innervation. In neonates, however, substantial rostrocaudal differences are apparent in dendritic complexity, number of axons innervating ganglion cells, and synaptic density. There is an associated delay in ganglion cell-target interactions in the lumbar region. My results show that rostrocaudal position is significantly correlated with the time course of dendritic growth and synaptogenesis and suggest that ganglion cell-target interactions may be important in these developmental processes. This difference in developmental rate, however, does not lead to differences in neuronal morphology or synaptic density between rostral and caudal ganglia in maturity.

Animals↗
PubMed1986

Relation of animal size to convergence, divergence, and neuronal number in peripheral sympathetic pathways.

The enormous range of animal size raises a fundamental problem: How do larger animals maintain adequate control of peripheral structures that are many times more massive and extensive than the homologous structures in smaller animals? To explore this question, we have determined neuronal number, the number of axons that innervate each neuron (convergence) and the number of neurons innervated by each axon (divergence), in a peripheral sympathetic pathway of several mammals (mouse, hamster, rat, guinea pig, and rabbit). The average adult weights of these species vary over approximately a 65-fold range. However, the number of superior cervical ganglion cells increases by only a factor of 4 between the smallest of these animals (mice; about 25 gm) and the largest (rabbits; about 1700 gm); the number of spinal preganglionic neurons that innervate the ganglion increases by only a factor of 2. Thus, the number of nerve cells in the sympathetic system does not increase in proportion to animal size. On the other hand, our results indicate that there are systematic differences across these species in the number of axons that innervate each ganglion cell and in the number of ganglion cells innervated by each axon. We suggest that modulation of convergence and divergence in sympathetic ganglia allows this part of the nervous system to effectively activate homologous peripheral targets over a wide range of animal size.

Animals↗
PubMed1983

Neurological complications of acquired immune deficiency syndrome: analysis of 50 patients.

Fifty patients with acquired immune deficiency syndrome had complications affecting the central or peripheral nervous systems or both. The patients were either male homosexuals, intravenous drug abusers, or recently arrived Haitian refugees. They ranged in age from 25 to 56. Central nervous system complications were of four kinds: (1) Infections included Toxoplasma gondii abscesses in 5 patients, progressive multifocal leukoencephalopathy in 2, cryptococcal meningitis in 2, Candida albicans in 1, and possible Mycobacterium avium intracellulare in 3. Eighteen patients suffered a subacute encephalitis possibly attributable to cytomegalovirus infection. (2) Tumors consisted of primary lymphoma of the brain in 3 patients and meningeal invasion by systemic lymphoma in 4. (3) Vascular complications included nonbacterial thrombotic endocarditis in 2 patients and cerebral hemorrhages in the setting of thrombocytopenia in 3. (4) Undiagnosed central nervous system problems were evidenced as focal brain lesions in 3 patients and self-limiting aseptic meningitis in 4. Peripheral neuropathy occurred in 8 patients.

Acquired Immunodeficiency Syndrome↗