摘要:

AbstractSeveral recently reported investigations have shown that a member of the neurotrophin family of neuronal growth factors, brain‐derived neurotrophic factor (BDNF), supports motoneuronsin vitroand rescues motoneurons from naturally occurring and axotomy‐induced cell death (Oppenheim et al., 1992b; Sendtner et al., 1992b; Yan et al., 1992; Koliatsos et al., 1993; Henderson et al., 1993). In the current study, we have explored the issue of whether BDNF and other neurotrophins act to regulate motoneuron survival during development and asked whether synthesis of motoneuron transmitter enzymes is also regulated. We first examined whether spinal motoneurons in newborn animals could retrogradely transport iodinated neurotrophins from their targets in a specific, receptor‐mediated manner. We found that motoneurons readily transported NGF, BDNF, and neurotrophin‐3 (NT‐3). The retrograde transport of one factor could be completely or largely blocked by excess of unlabeled homologous factor, but only partially blocked by excess of unlabeled heterologous factors. Since previous studies have shown that these three neurotrophins bind to the low‐affinity NGF receptor, p75NGFR, with similar affinity, our data suggest that the retrograde transport of neurotrophins by motoneurons may be mediated by additional components, such as thetrkfamily of proto‐oncogenes. Consistent with this hypothesis, we demonstrate here that motoneurons express mRNA for two members of thetrkfamily,trkB andtrkC. Furthermore, bothtrkB andtrkC were expressed by E13, consistent with a role for BDNF and NT‐3 in regulating important developmental events involving motoneurons such as naturally occurring cell death. In order to determine which members of the neurotrophin family influence motoneuron survival and to assess the generality of their effects, we evaluated the abilities of NGF, BDNF, and NT‐3 to save both spinal and cranial motoneurons after neonatal axotomy. Locally applied BDNF saved 40–70% of motoneurons which would ordinarily die after axotomy in lumbar and cranial motor pools, depending on the treatment protocol employed. NT‐3 also exhibited some ability to rescue motoneurons and saved 20–25% of motoneurons which would die in the absence of treatment. Finally, we asked whether neurotrophins could influence synthesis of transmitter enzymes by motoneurons as well as their survival after axotomy. Locally applied BDNF and NT‐3 could partially prevent the decrease of protein contents in L4and L5ventral roots which normally follows sciatic nerve transection. However, treatment with these neurotrophins did not prevent the decrease in choline acetyltransferase (ChAT) activity in L4and L5ventral roots which results from this procedure. These results suggest that BDNF and NT‐3 are among the growth factors that regulate motoneuron developmentin vivo, but that their actions may be more restricted than those of the prototypical factor, NGF, on its responsive neurons.

ISSN:0022-3034    

DOI:10.1002/neu.480241202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractTreatment of chick embryosin ovowith IGF‐I during the period of normal, developmentally regulated neuronal death (embryonic days 5–10) resulted in a dose‐dependent rescue of a significant number of lumbar motoneurons from degeneration and death. IGF‐II and two variants of IGF‐I with reduced affinity for IGF binding proteins, des(1‐3) IGF‐I and long R3IGF‐I, also elicited enhanced survival of motoneurons equal to that seen in IGF‐I‐treated embryos. IGF‐I did not enhance mitogenic activity in motoneuronal populations when applied to embryos during the period of normal neuronal proliferation (E2‐5). Treatment of embryos with IGF‐I also reduced two types of injury‐induced neuronal death. Following either deafferentation or axotomy, treatment of embryos with IGF‐I rescued approximately 75% and 50%, respectively, of the motoneurons that die in control embryos as a result of these procedures. Consistent with the survival‐promoting activity on motoneuronsin ovo, IGF‐I, ‐II, and des(1‐3) IGF‐I elevated choline acetyltransferase activity in embryonic rat spinal cord cultures, with des (1‐3) IGF‐I demonstrating 2.5 times greater potency than did IGF‐I. A single addition of IGF‐I at culture initiation resulted in the maintenance of 80% of the initial ChAT activity for up to 5 days, during which time ChAT activity in untreated control cultures fell to 9%. In summary, these results demonstrate clear motoneuronal trophic activity for the IGFs. These findings, together with previous reports that IGFs are synthesized in muscle and may participate in motoneuron axonal regeneration and sprouting, indicate that these growth factors may have an important role in motoneuron development, maintenance, and re

ISSN:0022-3034    

DOI:10.1002/neu.480241203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractDuring postembryonic development, the DD motoneurons in the nematodeCaenorhabditis eleganscompletely reorganize their pattern of synapses. Ablation of a pair of embryonic precursors results in the absence of this entire class of motoneurons. In their absence animals exhibit two developmentally distinct locomotory defects. The transition period from one defect to the other is correlated with the synaptic reorganization of the DD mns. Mutations in a gene (unc‐123) have been isolated that exhibit locomotory defects similar to those of the ablated adult animals. Genetic and cellular analyses of one of these alleles suggest that theunc‐123gene product may be involved in the reestablishment of functional synapses in these neurons. © 1993 John Wiley&Sons,

ISSN:0022-3034    

DOI:10.1002/neu.480241204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe properties of calcium channels were studied at the period of neurogenesis in the early embryonic chick retina. The whole neural retina was isolated from embryonic day 3 (E3) chick and loaded with a Ca2+‐sensitive fluorescent dye (Fura‐2). The retinal cells were depolarized by puff application of high‐K+solutions. Increases in intracellular Ca2+concentrations were evoked by the depolarization through calcium channels. The type of calcium channel was identified as l‐type by the sensitivity to dihydropyridines. The Ca2+response was completely blocked by 10 μMnifedipine, whereas it was remarkably enhanced by 5 μMBay K 8644. Then we sought a factor to activate the calcium channel and found that GABA could activate it by membrane depolarization at the E3 chick retina. Puff application of 100 μMGABA raised intracellular Ca2+concentrations, and this Ca2+response to GABA was also sensitive to the two dihydropyridines. Intracellular potential recordings verified clear depolarization by bath‐applied 100 μMGABA. The Ca2+response to GABA was mediated by GABAAreceptors, since the GABA response was blocked by 10 μgMbicuculline or 50 μMpicrotoxin, and mimicked by muscimol but not by baclofen. Neither glutamate, kainate, nor glycine evoked any Ca2+response. We conclude that l‐type calcium channels and GABAAreceptors are already are already expressed before differentiation of retinal cells and synapse formation in the chick retina. A possibility is proposed that GABA might act as a trophic factor by activating l‐type calcium channels via GABAAreceptors during the early period of retinal neurogenesis. © 1993

ISSN:0022-3034    

DOI:10.1002/neu.480241205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractInXenopus laevis, the sexual differentiation of the neuromuscular system responsible for courtship song is controlled by testicular androgen secretion. To explore the sensitivity of this system to androgenic stimulation, male and female frogs were gonadectectomized and given testis transplants at seven different developmental stages between the end of metamorphosis and adulthood, grown to sexual maturity, and the laryngeal muscle fibers and motor axons were counted. Muscle fiber and axon numbers in males were not affected by the testicular transplant at any stage. In females, testicular transplants at all developmental stages increased muscle fiber numbers in adulthood. Values attained were, however, significantly less than those of adult intact or testis‐transplanted males. Testis transplantation increased laryngeal axon numbers in females to levels equivalent to those of intact males; this effect was obtained at every stage of postmetamorphic development including adulthood. To further explore androgen regulation in adults, males and females were gonadectomized and implanted with silicone tubes containing testosterone propionate for 1.5–3 years and laryngeal muscle fibers and axon numbers compared to those of gonadectomized or sham‐operated adult controls. Neither treatment with exogenous androgen nor gonadectomy had any effect on laryngeal muscle fiber or axon number in either males or females; values did not differ from those of sham‐operated controls. We conclude that testicular secretions can induce laryngeal muscle fiber and axon addition in females throughout postmetamorphic life. This degree of plasticity, exhibited after the period when adult values are normally attained, stands in contrast to the effects of administration of synthetic androgen and suggests that the degree of plasticity in adult females may be underestimated if exogenous hormones rather than testicular transplants are provided. © 1993 John Wiley&S

ISSN:0022-3034    

DOI:10.1002/neu.480241206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractNeurotrophin‐3 is mitogenic for cultured quail neural crest cells (Kalcheim et al., 1992,Proc. Natl. Acad. Sci. USA89:1661–1665). We now report that neurotrophin‐3 also influences the survival and/or differentiation of a subset of postmitotic neural crest precursors into neurons, provided these progenitors are grown on a cellular substrate. When cultured for 1 day on monolayers of NT‐3‐producing, chinese hamster ovary cells, 59% of the neural crest clusters growing on the transfected line revealed the presence of intense neuronal outgrowht, compared to 25% of that in controls. Moreover, dissociated neural crest cells grown for 20 h on top of mesodermal cells in the presence of various concentrations of purified recombinant neurotrophin‐3 displayed a dose‐dependent increase in neuronal number. Localization experiments using specific polyclonal antibodies, revealed that neurotrophin‐3 is confined to neuroepithelial cells of quail neural tubesin situon E2 and E3, and to E2 neural tubes grown in culture for 24 h. At this stage, neural crest cells and somites were negative. At later stages, staining was likewise apparent in peripheral nerves and dorsal root ganglia. We, therefore, propose that NT‐3, a factor that is expressed in the early avian central nervous system, has multiple effects both on the proliferation and differentiation of distinct neural crest cells, which depend on the state of committment of the responsive progenitors. © 1993 Jo

ISSN:0022-3034    

DOI:10.1002/neu.480241207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractHouseflies (Musca domestica) were exposed to pulses of heat (1 h) or cold (several hours) during early pupal life, and the effects were investigated on the development of the first optic neuropile, or lamina, of the visual system. The treatments were designed to perturb the cellular or ganization of the cartridges, the unit synaptic structures of the lamina, so as to provide novel synaptic opportunities amongst the normally fixed composition of these modules, thereby testing the preferences of their component cells during synaptogenesis. Various abnormalities were identified, but these were not always consistent between flies: retinal abnormalities included the loss and fusion of rhabdomeres, especially of the central cells of the ommatidium, whereas in the lamina low frequencies of abnormal cartridges were found. These included seven that were studied with serial sections, which instead of the normal pair of L1 and L2 monopolar interneurons had supernumerary cells of this type. The normal pairing of L1 and L2 at postsynaptic sites of receptor terminal tetrad synapses was preserved in these cases, the cells eschewing pairings of homologous L1/L1 or L2/L2 partners. This meant that more than one L1 could pair with a single L2 and vice versa, even at the same terminal, and appeared to do so opportunistically on the basis of proximity, with cells closer to each other pairing more frequently. Thus the cells behave during synaptogenesis as if theyrecognizeother cells only as cell types (receptor, L1 or L2) and not as individual cells. © 1993 John Wiley&Sons, Inc

ISSN:0022-3034    

DOI:10.1002/neu.480241208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

ISSN:0022-3034    

DOI:10.1002/neu.480241201

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY