摘要:

AbstractMicrodialysis was used in the freely moving rat to measure the effects of graded changes in brain glucose on the serotonergic and noradrenergic projections to the hippocampus. The concentration of glucose in the dialysate was monitored using an enzyme‐based assay. A systemic injection of insulin caused a steep decline in glucose level which was restored to the control level by oral administration of glucose solution. The changes in 5‐hydroxytryptamine (5‐HT) and noradrenaline were a mirror image of the glucose changes: they rose after insulin injection and returned to control during glucose administration. A delayed increase was shown by 5‐hydroxyindoleacetic acid (5‐HIAA) which did not return to baseline on glucose administration. The metabolite dihydroxyphenylacetic acid (DOPAC) decreased after insulin administration and increased above control during glucose administration. While the responses of 5‐HT, noradrenaline and 5‐HIAA to hypoglycaemia resemble those to mild stress, the changes in DOPAC are the reverse of those produ

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb01053.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe long‐term structural and functional consequences of transient forebrain ischaemia were studied with morphological, immunohistochemical andin vitroelectrophysiological techniques in the primary somatosensory cortex of Wistar rats. After survival times of 10–17 months postischaemia, neocortical slices obtained from ischaemic animals were characterized by a pronounced neuronal hyperexcitability in comparison with untreated age‐matched controls. Extra‐and intracellular recordings in supragranular layers revealed all‐or‐none long‐latency recurrent responses to orthodromic synaptic stimulation of the afferent pathway. These responses were characterized by durations up to 1.7 s, by multiple components and by repetitive synaptic burst discharges. The reversible blockade of this late activity bydl‐aminophosphonovaleric acid (APV) suggested that this activity was mediated by Kmethyl‐l‐aspartate (NMDA) receptors. The peak conductance of inhibitory postsynaptic potentials was significantly smaller in neurons recorded in neocortical slices obtained from ischaemic animals than those from the controls. However, the average number of parvalbumin (PV)‐labelled neurons per mm3, indicative of a subpopulation of GABAergic interneurons, and the average number and length of dendritic processes arising from PV‐containing cells was not significantly different between ischaemic and control cortex. The prominent dysfunction of the inhibitory system in ischaemic animals occurred without obvious structural alterations in PV‐labelled cells, indicating that this subpopulation of GABAergic interneurons is not principally affected by ischaemia. Our data suggest a long‐term down‐regulation of inhibitory function and a concurrent NMDA receptor‐mediated hyperexcitability in ischaemic neocortex. These alterations may result from structural and/or functional properties of inhibitory non‐PV‐positive neurons or permanent functional modifications on the subcellular molecular level, i.e. alterations in the phosphorylation status of GABA and/or NMDA receptors. The net result of these long‐term changes is an imbalance between the excitatory and inhibitory systems in the ischaemic cortex with the subsequent expression and manifestati

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb01054.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractFocal epileptic activity can be expected to influence distant brain areas via far reaching connections. To investigate such interactions the effects of focal epileptic activity on the metabolism of the brain were investigated in the rat cortex. Focal epileptic activity was induced by the application of penicillin onto the motor cortex. The focus, and to a lesser extent homotopic contralateral brain areas, showed an increase in the regional cerebral metabolic rate of glucose (rCMRGIc) as measured by [14C]deoxyglucose autoradiography. This focal hypermetabolism was accompanied by widespread hypometabolism lateral to the focus. The decrease ofrCMRGIc occurred in somatosensory cortical areas but not in the motor cortex behind or in front of the focus, the perirhinal cortex or the occipital cortex. It was associated with an increase in metabolic rate in the ventrolateral, ventroposteromedial, ventroposterolateral and, in particular, posterior nuclei of the thalamus. It is hypothesized that the widespread reduction ofrCMRGIc in the somatosensory cortical areas is due to inhibition via thalamic nuclei caused by activity in the motor cortex.

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb01055.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThis study reports the spatio‐temporal pattern of BEN expression (a molecule of the immunoglobulin superfamily) during early stages of the first axonal tract formation, in the fore‐ and midbrain of chick embryos [Hamburger and Hamilton (HH) stages 12–22]. The expression of BEN has been analysed using immunohistochemistry and non‐radioactivein situhybridization. Furthermore, double labelling experiments (combining anti‐class III β‐tubulin, a pan‐neuronal marker, and anti‐BEN antibodies) have been carried out to determine whether BEN is expressed by all first axonal tracts. The first neurons expressing BEN appear around stage HH13–14, in the caudal diencephalon. They belong to the interstitial nucleus of Cajal, and their axons are the first components of the medial longitudinal fasciculus. By HH14, two other early axonal tracts appear: the tract of the postoptic commissure and the descending root of the mesencephalic nucleus of the trigeminal nerve. Only the latter expresses BEN. At later stages of development numerous new axonal tracts appear in the telencephalic, diencephalic and mesencephalic domains. Only a few of them (the fourth nerve, the lemniscus lateralis, the tectobulbar and habenulopeduncular tracts) express BEN. In all BEN positive systems, the cell bodies, axons and growth cones are uniformly labelled by the antibody. We have found that none of the early axonal tracts grows preferentially at interneuromeric boundaries. Moreover, each tract is formed by several thin fascicles rather than a single one. The expression of BEN is transient and disappears shortly before hatching. These results suggest that BEN may serve to promote axonal outgrowth of precise neuronal systems involved in

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb01056.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe neurotrophins, brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3), neurotrophin 4/5 (NT‐4/5) and nerve growth factor (NGF), were compared for their effects on the survival and differentiation of embryonic rat striatal neurons grown in low‐density cultures. Treatment with BDNF for 8 days resulted in a 40% increase in overall neuronal survival, a 3‐ to 5‐fold increase in the number of calbindin‐immunoreactive neurons, and an 80% increase in GABA‐positive neurons. Treatment with NT‐3 or NT‐4/5 produced a 2‐ to 3‐fold increase in the number of calbindin‐positive neurons and an increase in GABA‐positive cell number similar to that induced by BDNF. BDNF treatment produced a striking morphological differentiation of striatal GABAergic neurons, which was characterized by a doubling of the number of neurite branch points, the total area of arborization and the perikaryal area compared to control cultures. All three of these factors increased high‐affinity GABA uptake 2‐fold. NGF had no effect on any of the parameters examined. Our results show that BDNF, NT‐3 and NT‐4/5 promote the survival and/or differentiation of calbindin‐immuno

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb01057.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe effect of the various neurotrophin family members on the morphological structure of dopaminergic neurons was compared in dissociated cultures of embryonic rat ventral mesencephalon. Cultures were maintainedin vitroin the presence of brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3), neurotrophin‐4/5 (NT‐4/5), nerve growth factor (NGF) or no added growth factors. Three‐dimensional reconstructions of 48 neurons were made in each of the experimental groups following immunocytochemical staining for tyrosine hydroxylase to detect dopaminergic neurons. In addition [3H]mazindol binding analyses were carried out in replicate cultures in order to quantify the effects of the neurotrophins on the number of dopamine uptake sites. Among the neurotrophins tested, NT‐4/5 influenced the proximal morphological parameters most, as determined by a 36% increase in the soma profile area and 35% in the number of stem neurites. Analysis of neuritic size and complexity in these cultures revealed that combined neuritic length and number of segments/cell were increased by 45 and 40% respectively. A change in neurite complexity in the NT‐4/5 treated cultures was further confirmed using Scholl's concentric sphere analysis. In addition, relative to the control, NT‐4/5 increased the neuronal differentiation as evidenced by increases in varicosity density and [3H]mazindol binding by 114 and 101% respectively. BDNF and, to a lesser extent, NT‐3 also increased both proximal parameters and parameters of differentiation, but were without effect on parameters of neuritic size and Complexity. No effects on neuronal structure were observed in NGF treated cultures. These findings demonstrate that BDNF, NT‐3 and NT‐4/5 influence the morphological differentiation of dopaminergic neuronsin vitro, suggesting they may play a role in the structural development and plasticity of these neuro

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb01058.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractWe are interested in analysing the detailed modulation of defined neuronal systems by multiple neuropeptides encoded in the FMRFamide locus of the snailLymnaea.Cloning of the FMRFamide gene has predicted the existence of two novel peptides previously unknown from biochemical analysis, the pentapeptides EFLRlamideand QFYRlamide. These peptides may form part of a new family of peptides sharing the sequence motif –FXRlamide. In this paper we adopt a novel approach to first identify and characterize –FXRlamide‐like peptides in extracts from the central nervous system ofLymnaea.By a combination of high‐performance liquid chromatography (HPLC) and continuous‐flow fast atom bombardment mass spectrometry, we identify three novel peptides: EFLRlamide, pQFYRlamide and pQFLRlamide. The first two are those predicted in exon II of the FMRFamide locus whereas the last is, interestingly, a product which cannot be derived from post‐translational modification of the predicted peptides but must be encoded by as yet unidentified nucleotide sequences. A specific antibody raised to EFLRlamide, and immuno reactive to all three peptides, revealed EFLRlamide‐like expression throughout the central nervous system in the same cells where exon II is transcribed and the peptide SEEPLY (a post‐translational product of exon II) was localized. Additional cells, however, were also identified. Immunoreactivity was mapped in a number of identified neurons in the central nervous system, including two heart cardio excitatory motoneurons, the Ehecells (E heart excitors of the visceral ganglion) and penialmotoneurons in the right cerebral ganglion. The peripheral tissues (heart and penial complex) that the serespective classes of neurons innervate also exhibited EFLRlamide immunoreactivity. The central and peripheral localization of EFLRlamide‐like immunoreactivity suggested that EFLRlamide/pQFYRlamide may have an important physiological role in both these peripheral systems as well as in the central nervous system. This was confirmed by physiological experiments that showed that EFLRlamide and pQFYRlamide inhibited many centralneurons and in particular the Bgp neurons in the right parietal ganglion. EFLRlamide had complex biphasic effects on the frequency of heart‐beat: an initial inhibitory response was followed by a long‐lasting increase in the rate of beating. Taken together with earlier work, this study now completes the analysis and localization of the full set of post‐translational products of the FMRFamide precursor inLymnaeaand supplies further evidence towards the characterization of the physiological systems which such peptides

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb01059.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThis study investigated the role of theN‐methyl‐d‐aspartate (NMDA) subtype of glutamate receptor in the induction of long‐term potentiation (LTP) in the hippocampal‐prefrontal cortex pathwayin vivo.Field potentials evoked by electrical stimulation of the CA1/subicular region were recorded in the prelimbic area of the prefrontal cortex under continuous perfusion of artificial cerebrospinal fluid in anaesthetized rats. High‐frequency stimulation of the CA1/subicular region induced LTP of the evoked response in the prelimbic area of the prefrontal cortex. LTP was completely blocked when the selective NMDA receptor antagonistd‐(‐)2‐amino‐5‐ phosphonopentanoic acid (d‐AP5; 200 μM), was perfused during the tetanus. Perfusion of D‐AP5 did not affect normal transmission or pre‐established LTP. These results demonstrate that induction of LTP in the hippocampal‐prefrontal cortex pathway is an N

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb01060.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractChronic dibutyryl cAMP (dbcAMP) treatment was observed not only to potentiate the differentiating actions of nerve growth factor (NGF) in PC12 cells, but to render them completely dependent on trophic support for survival even in the presence of serum proteins. When both NGF and dbcAMP were withdrawn from doubly differentiated PC12 cultures, degenerative events occurred after a lag period of 12–18 h, and by 48 h ≤ 5–10% of the cells remained viable. Reduction in [3H]dopamine uptake, an index of cell function and neurite integrity, paralleled cell demise. At the cellular level, ∼20–30% of the nuclei exhibited clear signs of chromatin fragmentation, as characterized by propidium iodide staining, suggesting that degeneration occurred by apoptosis. The cells could be rescued completely from degeneration by dbcAMP or by other cAMP analogues, whereas NGF and depolarization were also effective, but only partially. Phorbol 12‐myristate‐13‐acetate failed to afford protection. If deprivation was interrupted, cell demise could be stopped by restoration of initial culture conditions. Degenerative changes produced by deprivation and recovery processes were not inhibited by macromolecular synthesis inhibitors, e.g. cycloheximide and actinomycin‐D. However, chronic addition of cycloheximide prior to deprivation greatly impaired the differentiation of NGF/dbcAMP cells, allowing these cells to withstand trophic support withdrawal. Altogether our results indicate that the cAMP transduction pathway plays a crucial role not only in the differentiation but also in the survival of NGF/

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb01061.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe role of synapsin I, a synaptic vesicle‐associated phosphoprotein, in the maturation of nerve–muscle synapses was investigated in nerve–muscle co‐cultures prepared fromXenopusembryos loaded with the protein by the early blastomere injection method. The stage of maturation of the synapses was analysed by electron microscopy as well as by whole‐cell patch‐clamp recording. The acceleration in the functional maturation of neuromuscular synapses induced by synapsin I was accompanied by a profound rearrangement in the ultrastructure of the nerve terminal. Nerve terminals formed by synapsin I‐loaded neurons were characterized by a higher number of small synaptic vesicles organized in clusters and predominantly localized close to the nerve terminal plasma membrane, a smaller number of large dense‐core vesicles and no significant change in the number of coated vesicles. Precocious development of active zone‐like structures as well as deposition of basal lamina into the synaptic cleft were also observed at these synapses. These results support a role for synapsin I in the architectural changes which occur during synaptogenesis and lead to the maturation of quantal neurotransmitter r

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb01062.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY