ISSN:0736-5748    

DOI:10.1016/S0736-5748(96)90000-3

出版商:Wiley    

年代:2005

数据来源: WILEY

摘要:

AbstractThe neuronal network of the adult central nervous system (CNS) retains a limited capacity for growth and structural change. This structural plasticity has been best studied in the context of lesion‐induced growth and repair. More recently, structural changes underlying functional plasticity occurring under specific physiological conditions have also been documented, in particular in the cortex and the hippocampus. Areas known for their adult plastic potential retain high levels of the growth associated protein GAP‐43, suggesting a persistence of important components of the intracellular growth machinery throughout life. Interestingly, a pronounced negative correlation exists between the levels of GAP‐43 and myelination in the adult CNS. Because CNS myelin contains potent neurite growth inhibitory membrane proteins, neurite growth, sprouting and plasticity were investigated in the spinal cord and brain in areas where oligodendrocyte development and myelin formation was experimentally prevented, or in the presence of an inhibitor neutralizing antibody (mAB‐IN‐1). In all areas, lesion‐induced or spontaneous sprouting was enhanced, in parallel with persistent high levels of GAP‐43. Thus, spontaneous sprouting of side branches occurred from retinal axons in the optic nerve in the absence of myelin, and target‐deprived retinal axons showed increased sprouting and innervation of the contralateral optic tectum in the presence of mAB IN‐1. In experimentally myelin‐free spinal cords collaterals from intact dorsal roots grew over long distances to innervate deafferented target regions following the section of three dorsal roots. Similarly, the corticospinal tract sprouted across the the midline and re‐established a dense plexus of fibres on the contralateral side of the spinal cord following section of one corticospinal tract in juvenile rats. Following bilateral dorsal hemisection of the spinal cord including both corticospinal tracts in young and adult rats, long distance regeneration of corticospinal fibres leading to significant functional improvements of locomotion and certain reflexes was induced by the neurite growth inhibitor neutralizing antibody IN‐1.

ISSN:0736-5748    

DOI:10.1016/0736-5748(96)00024-X

出版商:Wiley    

年代:2005

数据来源: WILEY

摘要:

AbstractThe effects of explants of optic nerves of different ontogenetic ages (P0‐P14, adult), and of cultured astrocytes of various ages on the neurite regeneration of rat retinal ganglion cells (RGC) were assessedin vitro, using a three‐dimensional culture system which allows the co‐cultivation of various explants. Both co‐cultured P0‐P12 optic nerves and astrocyte cultures from P2 cerebral cortex stimulated the regeneration of neurites from the retinal explants after 3 days in culture. By contrast, P14 and older explants of the optic nerve, astrocytes from P17 optic nerve and astrocytes that had previously been grown in culture for more than 6 weeks had no effect on RGC neurite outgrowth. Moreover, both the P0–P12 optic nerve explants and the astrocytes from P2 cerebral cortex also seemed to have a chemotropic effect on the regenerating neurites, because the latter were longer on the side facing the co‐explantat. The absence of a cellular bridge between retinal and optic nerve explants suggests that the effects are mediated by astroglia‐derived diffusible neurite growth promoting factors. Accordingly, astrocyte‐conditioned medium from P2 astrocytes also stimulated the outgrowth of neurites from the retinal explants. These findings show that immature astrocytes of a limited ontogenetic period release as yet unknown diffusible neurite growth‐promoting factors which stimulate the regeneration of neurites from retinal explants.

ISSN:0736-5748    

DOI:10.1016/0736-5748(96)00031-7

出版商:Wiley    

年代:2005

数据来源: WILEY

摘要:

AbstractThe effects of acute perinatal ischemia‐hypoxia on fetal liver and brain energy metabolism, fetal brain total free fatty acid concentration and subsequent offspring behavior were investigated in rats. Ischemia‐hypoxia was induced at term either by ligation of the uterine blood vessels or submersion of the entire uterine horn in warmed saline. Fetuses of the adjacent horn served as within‐dam controls for all assessments and fetuses of dams which had not undergone the surgical stress served as independent controls for enzyme assays. Ischemia‐hypoxia was associated with reduced activity of fatty acid synthase in the liver and brain. Total free fatty acid concentration significantly increased in the fetal hypoxic brain. Pups not used for enzyme analyses were cross‐fostered for behavioral assessments. Relative to the enzymatic alterations, there were few behavioral alterations associated with ischemia‐hypoxia. At postnatal day 30, rats made hypoxic by ligation of the uterine blood vessels had decreased caudate nucleus and brain stem weights relative to within‐dam controls. At postnatal day 85, rats made hypoxic by submersion of the uterine horn had decreased olfactory bulb weight. The results of this study indicate an initial acute response to a brief period of ischemia‐hypoxia at term pregnancy in the fetal rat brain and liver.

ISSN:0736-5748    

DOI:10.1016/0736-5748(96)00025-1

出版商:Wiley    

年代:2005

数据来源: WILEY

摘要:

AbstractThe effect of different hormones and growth factors was assayed on thein vitrogrowth and enzymatic activities of 2′,3′‐cyclic nucleotide 3′phosphohydrolase (CNP) and glutamine synthetase (GS) of rat glioma C6 cells at two different passages in culture. Young cultures (passage 26), mainly oligodendrocytic, and older cultures (passage 134), predominantly astrocytic, were treated with 10 μM dexamethasone, 20 ng/ml transforming growth factor alpha (TGFα), 10 ng/ml insulin, 20 ng/ml platelet‐derived growth factor (PDGF), and 20 ng/ml, epidermal growth factor (EGF) in serum‐free chemically defined media.In vitrogrowth rate was measured in terms of DNA content, by a fluorometric method of diaminobenzoic acid, and rate of DNA synthesis by3H‐thymidine incorporation. CNP activity (marker forin vitrooligodendrocytes) and GS activity (marker for astrocytes) were determined spectrophotometrically. Dexamethasone reversibly and significantly inhibited growth of C6 glioma in early and late passages. PDGF and insulin promotedin vitrogrowth only in late passage but not in early passage cells, whereas EGF and TGFα did not significantly affect growth. An increase in CNP activity was observed in early passage cells under the effect of PDGF and insulin. The increase in GS activity induced by insulin and dexamethasone suggests a differentiating role for these factors in C6 glioma cells. These results further present the C6 glioma cell line as a useful model for studies on glial cell properties and responsiveness in culture and support its use in experimental agingin vitro.

ISSN:0736-5748    

DOI:10.1016/0736-5748(96)00026-3

出版商:Wiley    

年代:2005

数据来源: WILEY

摘要:

AbstractCells of the neural tube are thought to be committed to form only the central nervous system, whereas the peripheral nervous system is believed to be derived from neural crest cells and from placodes, which are specialized regions of the surface ectoderm. Neural crest cells arise early from the dorsal part of the neural tube. The possibility that after emigration of the neural crest cells, another population of cells arising from the ventral part of the neural tube also emigrates via a different route was examined. Here we report that, after labeling cells of the ventral neural tube in the rostral hindbrain of E3 duck embryos with DiI, they were later found in the trigeminal ganglion of the fifth cranial nerve. A trail of labeled cells could be traced from the ventral part of the neural tube to the peripheral ganglion. Further, expression of the homeobox gene Islet‐1 in cells of the neural tube and the ganglion also indicated that some ventral neural tube cells may normally emigrate to the trigeminal ganglion. It is concluded that not all neural tube cells are committed to form the central nervous system; the ventral part of the neural tube also provides cells for the formation of the trigeminal ganglion. These results raise the possibility that the ventral neural tube may serve as an additional source of cells for the formation of various other components of the peripheral nervous system.

ISSN:0736-5748    

DOI:10.1016/0736-5748(96)00002-0

出版商:Wiley    

年代:2005

数据来源: WILEY

摘要:

AbstractThe interrelations between migratory Purkinje cells and radial glial processes were examined immunohistochemically and electron‐microscopically in the fetal mouse cerebellum. Migratory Purkinje cells identified immunochemically with anti‐spot 35 antibody were apposed to the presumed radial glial processes. Putative immature migratory Purkinje cells were apposed to the radial glial processes identified immunochemically with monoclonal antibody 1DI I or anti‐tenascin antibody. Junctional specializations related to cell adhesion were observed at the sites of contact between the immature neurons and glial processes. Furthermore, coated vesicles and coated pits were noted in the contact region. These findings support the concept of contact guidance of migratory Purkinje cells by radial glial processes through cell adhesion, and also suggest the trophic interactions occurring at the region of contact.

ISSN:0736-5748    

DOI:10.1016/0736-5748(96)00021-4

出版商:Wiley    

年代:2005

数据来源: WILEY

摘要:

AbstractWe have shown previously that a soluble factor(s) released by the myenteric plexus promotes neurite outgrowth from postnatal striatal neurons, and that this effect was abolished by tetrodotoxin. We have now investigated the possible involvement of purines in the mediation of this neuritogenic response, by examining their effect on neurite length of striatal neurons both in co‐culture with myenteric plexus explants and cultured alone.Both ATP and 2‐chloroadenosine partially reversed the inhibitory effect of tetrodotoxin in co‐cultures with whole myenteric plexus, while the stable ATP analogue, α,β‐methylene ATP, had no effect, suggesting that ATP was being broken down to adenosine before exerting its action. Further support for this view was that the ATP (P2) purinoceptor antagonist suramin did not reverse the effects of ATP, while the adenosine (P1) purinoceptor antagonist 8‐(p‐sulphophenyl)theophylline did antagonize the effects of ATP in tetrodotoxin‐treated co‐cultures. Further, both 8‐(p‐sulphophenyl)theophylline and adenosine deaminase reduced the effect of the myenteric plexus on striatal neurons in the absence of tetrodotoxin, and the adenylate cyclase activator forskolin completely reversed the effect of tetrodotoxin in our co‐culture system.The neurite outgrowth‐promoting effect of 2‐chloroadenosine in tetrodotoxin‐treated co‐cultures was not further enhanced by a combination of neuropeptides. Serotonin and GTP were without effect on striatal neurons in the presence or absence of myenteric plexus explants. In experiments without myenteric plexus, both 2‐chloroadenosine and forskolin caused a slight increase in striatal neurite length; ATP and GTP were ineffective. Basic fibroblast growth factor, nerve growth factor, neurotrophin‐3 or neurotrophin‐4/5 had no effect on neurite outgrowth in postnatal striatal cultures after two daysin vitro. When these growth factors were added in combination with 2‐chloroadenosine, the observed increase in mean neurite length did not exceed that induced by 2‐chloroadenosine alone. Both 2‐chloroadenosine and the ganglioside mix AGF1 increased neurite elongation of striatal neurons after two daysin vitro, but an inhibition of enhanced neurite outgrowth was observed when both substances were added together. Both laminin and fibronectin were not neuritogenic for postnatal striatal neurons under our culture conditions. These observations suggest that a factor other than the growth factors tested here is involved in the promotion of striatal neurite outgrowth in co‐culture with myenteric plexus explants.In summary, adenosine (probably acting through the A2subclass of the P1 purinoceptor) leads to increased striatal neurite outgrowth in co‐culture with myenteric plexus and we propose that it does so either (1) by triggering the release of a neuritogenic factor, possibly from enteric glial cells, or (2) by acting synergistically with such a growth factor. Adenosine acts via PI purinoceptors, which leads to changes in cyclic AMP, and the response to forskolin suggests that cyclic AMP is probably involved in the events leading to increased striatal neurite outgrowth.

ISSN:0736-5748    

DOI:10.1016/0736-5748(96)00020-2

出版商:Wiley    

年代:2005

数据来源: WILEY

摘要:

AbstractThe substantia nigra of gestation day 14 was transplanted into the striatum of 3–4‐month‐old rats to investigate the transplants ultrastructurally at the end of 2 years, as a follow‐up to our previous studies. Transplants were of small size in all 10 specimens taken for this study. The changes observed in the transplant and in the interface region with the host striatum were: thickening of the blood vessel walls, perivascular cuffing with lymphocytes and macrophages loaded with tissue debris, degenerating neurons and hypertrophied astroglia containing dense granules indicating ageing or reaction to degeneration and glial processes. The number of surviving neurons in the transplants was small. These were smaller in size and had very few intracytoplasmic membraneous organelles. A higher content of intracytoplasmic ageing lipofuscin pigment was present than in host neurons and age‐matched nigral neurons. Synapses were few, and their number varied among transplants. Generally, the synapses were at the interface with the host tissue. The changes observed in all the 2‐year‐old transplants suggest premature ageing or a slow rejection process. Slow rejection is a possibility, because these rats are only stock‐bred, not inbred, and hence they are not completely immunologically compatible.

ISSN:0736-5748    

DOI:10.1016/0736-5748(96)00003-2

出版商:Wiley    

年代:2005

数据来源: WILEY

摘要:

AbstractIn contrast to the well known effects of prenatal ethanol exposure on the central nervous system, data about its peripheral effects are scarce. Here, Sprague‐Dawley rats were fed a liquid diet (gestational days 0–20) containing 36% ethanol‐derived calories (EDCs, group H) or were pair‐fed with 18% EDCs (group L) or 0% EDCs (group C. On postnatal day 20, one male and one female from each of 10 litters per group were killed. Norepinephrine (NE) was analyzed in the frontal cortex, spleen and thymus, and dopamine, 5‐hydroxytryptamine (serotonin, 5‐HT) and their metabolites 3,4‐dihydroxyphenylacetic acid, homovanillic acid (HVA) and 5‐hydroxyindoleacetic acid (5‐HIAA) were analyzed in the striatum by high‐performance liquid chromatography with electrochemical detection. Lymphocyte subpopulations in the spleen and thymus were also assessed in half of these litters. Significant decreases in splenic NE concentration were seen in both sexes of group H (males 27%, females 28%). Decreases in striatal 5‐HT and 5‐HIAA of group H subjects appeared to be sex specific (only females were significantly affected: 23% decrease in 5‐HT, 37% decrease in 5‐HIAA). Pronounced, dose‐dependent reductions in T cell percentages were observed in both the thymus and spleen. Splenic CD8+and CD4+cell percentages were positively correlated with the splenic NE concentrations. It is concluded that the decreases seen in splenic T cell percentages subsequent to prenatal ethanol exposure may be caused, at least partially, by impaired noradrenergic control of this organ.

ISSN:0736-5748    

DOI:10.1016/0736-5748(96)00001-9

出版商:Wiley    

年代:2005

数据来源: WILEY