摘要:

AbstractThe axonal growth‐associated protein GAP‐43 is believed to play some role in the synaptic remodelling that takes place in the hippocampus of adult rats after certain experimental lesions. GAP‐43 mRNA is highly expressed in adult CA3 pyramidal cells but almost absent in the dentate granule cells. We analysed whether the sprouting of granule cell axons, the mossy fibres of the hippocampus, caused by kainic acid‐induced seizures in adult rats was associated with any induction of GAP‐43 mRNA in granule cells and with any changes in the immunostaining pattern of GAP‐43 in the hippocampus. Increased GAP‐43 mRNA expression was found to be induced in granule cells 18, 24 and 30 h after a systemic injection of kainic acid which induced generalized seizures in adult rats, and returned to control levels by 48 h post‐treatment. No effect was observed in other regions of the hippocampus. However, when kainic acid was injected into 15‐day‐old rats, which responded with generalized seizures but no sprouting of mossy fibres, there was no induction of GAP‐43 mRNA in the granule cells, suggesting a close relation between GAP‐43 expression and sprouting of these cells. Seven days after kainic acid injections, GAP‐43 immunostaining was decreased in the inner molecular layer of the dentate gyrus except for a thin supragranular band, whereas 30 days after treatment all animals showed increased GAP‐43 immunoreactivity in the whole inner molecular layer. Since collaterals of mossy fibres grow in the inner molecular layer after kainic acid‐induced seizures, these results support the theory that GAP‐43 plays a role in synaptic remodelling in t

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00294.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractIn the C57BL/Ola (Ola) mouse strain there is a marked slowing of axonal disintegration during Wallerian degeneration. The locus of the mutation controlling this phenomenon (slow Wallerian degeneration‐Wlds) has been mapped to chromosome 4, and its protective effect decreases with advancing age. Using biochemical, electrophysiological and histological techniques, the present study was undertaken to determine whether neurofilament phosphorylation and stability are altered or whether calcium‐activated proteases are absent in the sciatic nerves of Ola mice. A compound action potential was detectable only when neurofilaments were present and normal axonal architecture was seen. In 1‐month‐old Ola mice, compound action potentials and neurofilaments were still detectable at 21 days post‐transection, whereas both were undetectable by 2 days in BALB/c and C57BL/6J (6J) mice of the same age. Neurofilament levels declined faster with advancing Ola age, confirming previous results, whereas degeneration slowed in ageing BALB/c and 6J mice.In vitroandin vivodegeneration rates were comparable in BALB/c and 6J nerves. Ola nerves, however, showed more rapid declinein vitrothanin vivo. Ola and BALB/c nerves frozen and then thawed and incubated in the presence of calcium ions and the ionophore A23187 were not resistant to degradation by intrinsic proteases. Even when a compound action potential could no longer be elicited, however, a majority of nerves still had>50% of myelinated and unmyelinated axons whose electron microscopic profiles appeared normal. Thus, it appears that the first event in Wallerian degeneration in the Ola mouse is a change at the plasma membrane‐a transected nerve becomes unable to conduct a compound action potential. Degeneration of the cytoskeleton is a later, sepa

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00295.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe avian archistriatum, part of which may be homologous with the mammalian amygdala, has been implicated in fear and avoidance behaviour. There is also evidence to suggest its involvement in learning. One‐trial passive avoidance learning (PAL) has been used extensively to study memory formation in the chick. Young chicks will peck spontaneously at a small, visually conspicuous bead. If the bead has been coated with an aversive substance, the chicks show a disgust response and learn in a single trial not to peck a similar bead on subsequent presentation. Successful acquisition of this one‐trial PAL task involves the formation of a learned association between the bead and a noxious taste, followed by the expression of an avoidance response. In view of the possible involvement of the archistriatum in avoidance and learning behaviour, its role in one‐trial PAL was investigated by ablation. Bilateral electrolytic lesions of the entire archistriatum prevented the acquisition of the one‐trial PAL task. Neither bilateral lesions of the lateral cerebral area nor sham operation affected learning. The impairment of one‐trial PAL caused by archistriatal lesions was not due to effects on the visual or motor components of pecking behaviour. The archistriatum could therefore be directly involved in memory formation. It could also be involved in the organization of avoidance behaviour associated with the task, or it could form part of a circuit linking two other forebrain regions previously implicated in one‐trial PAL, the intermediate part of the medial hyperstriatum ventrale and the lobus par

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00296.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe subcellular distribution of the plasma membrane ectoenzymes, aminopeptidase N (aminopeptidase M) and dipeptidyl peptidase IV, has been examined by fractionating homogenates of porcine striata by a discontinuous Percoll gradient centrifugation procedure which distinguishes fractions containing pre‐ and post‐synaptic elements. The two enzymes showed different distributions–dipeptidyl peptidase IV did not show a significant pre‐synaptic location, whereas aminopeptidase N was present on both pre‐ and post‐synaptic fractions. Immunofluorescent staining on mixed and neuron‐enriched primary cultures of pig striatal tissue using affinity purified antibodies to the aminopeptidase and to the dipeptidyl peptidase revealed the ectoenzymes on distinct populations of cells. The astrocytic identity of the aminopeptidase N‐staining cells was established by correlation with immunostaining for glial fibrillary acidic protein and for vimentin by confocal microscopy. Ultracryosections of striatum immunostained with gold‐labelled immunoglobulins of differing diameters demonstrated aminopeptidase N on pericytes and confirmed its location on endothelial and astrocytic glial cells. Thus, several independent approaches indicated that aminopeptidase N, in addition to being present on endothelial and synaptic membranes, is found on astrocytes and pericytes in the perivascular neuropil, whereas dipeptidyl peptidase IV is less widely distributed on microvessels and appears not to have a syna

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00297.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractCreatine kinase isoenzymes were localized in the chicken cerebellum by the use of isoenzyme‐specific anti‐chicken creatine kinase antibodies. Brain‐type creatine kinase was found in high amounts in the molecular layer, particularly in Bergmann glial cells but also in other cells of the cerebellar cortex, e.g. in astrocytes and in the glomerular structures, as well as in cells of the deeper nuclei. A mitochondrial creatine kinase isoform was primarily localized to the glomerular structures in the granule cell layer and was also identified in Purkinje neurons. Surprisingly, a small amount of the muscle‐type creatine kinase isoform was identified in cerebellar extracts by immunoprecipitation, immunoblotting and native enzyme electrophoresis, and was shown to be localized exclusively in Purkinje neurons. Cell type‐specific expression of brain‐ and muscle‐type creatine kinase in Bergmann glial cells and Purkinje neurons, respectively, may serve to adapt cellular ATP regeneration to the different energy requirements in these specialized cell types. The presence of brain‐type creatine kinase in Bergmann glial cells and astrocytes is discussed within the context of the energy requirements for ion homeostasis (K+resorption), as well as for metabolite and neurotransmitter trafficking. In addition, the presence of muscle‐type creatine kinase in Purkinje neurons, which also express other muscle‐specific proteins, is discussed with respect to the unique calcium metabolism of these neurons and their role in cerebe

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00298.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe time‐course and extent of death of retinal ganglion cells (RGCs) following ablation of the superior colliculus (SC) in neonatal Wistar rats has recently been described [Harvey, A. R. and Robertson, D. (1992)J. Comp. Neurol.,325, 83–94]. Normal and pyknotic nuclei of retinotectally projecting ganglion cells were visualized using the fluorescent retrograde tracer diamidino yellow (DY), which had been injected into the SC at P2 (day of birth = P0), 2 days prior to tectal removal. The present report sets out to determine whether cycloheximide, an inhibitor of protein synthesis, or ganglioside GM1 reduced this lesion‐induced RGC death. All surgery was carried out under ether anaesthesia; DY was injected into the left SC at P2 and the injected area was removed at P4. Cycloheximide (20‐500 ng) was injected into the vitreous chamber of the right eye immediately after the lesion and again 11 ‐12 h later. In some rats, cycloheximide administration was delayed until 12 h after the SC ablation. Control rats received SC lesions alone or lesions plus sham eye injections of saline. Different doses of GM1 were applied i.p. or intraocularly. Rats were perfused 24 h after the SC lesion, at the time of peak RGC death. Retinae of lesion only or sham eye injected rats contained ‐11% pyknotic RGCs and the density of normal RGCs was ‐3400/mm2. The rate of pyknosis in cycloheximide treated retinae was reduced to ‐3%. Normal RGC density in these retinae was ∼5500/mm2, similar to that found in retinae of unlesioned animals. Delaying the application of cycloheximide significantly reduced its effectiveness in preventing RGC death. GM1 treatments had no, or only minor, impact on RGC pyknosis 24 h after SC removal. The data are consistent with the proposal that RGC death after neonatal loss of central target sites is an active process that requires protein synthesis. It is therefore possible that, in the developing mammalian visual system, target‐derived neurotrophic factors maintain RGC viability by suppressing some form of endogenous suicide program

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00299.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractMorphologically, a GABAergic connection between the medial terminal nucleus of the accessory optic system and the nucleus of the optic tract, two primary visual nuclei involved in the optokinetic reflex, has been demonstrated. In this study it was investigated if the medial terminal nucleus forms an inhibitory input to movement direction selective units in the nucleus of the optic tract. Neurons in the nucleus of the optic tract were visually stimulated with moving large random square patterns in their preferred and non‐preferred direction, and their activity was recorded extracellularly. Concomitantly, bipolar electrical stimulation was applied to the medial terminal nucleus and its effect was studied on the visual responses of units in the nucleus of the optic tract. Units in the nucleus of the optic tract were strongly inhibited during electrical stimulation of the medial terminal nucleus. The role of GABA in mediating this inhibition was investigated by applying bicuculline, a GABAAreceptor antagonist, iontophoretically to the recorded units in the nucleus of the optic tract. However, although average spike rate levels of units in the nucleus of the optic tract increased with bicuculline, bicuculline did not reduce inhibition invoked by electrical stimulation of the medial terminal nucleus. A possible explanation for this observation is that this inhibition is GABABreceptor mediate

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00300.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractVestibular compensation is an attractive model for investigations of cellular mechanisms underlying post‐lesional plasticity in the adult central nervous system. Immediately after hemilabyrinthectomy, the spontaneous activity in the deafferented second‐order vestibular neurons falls to zero, resulting in a strong asymmetry between the resting discharge of the vestibular complexes on the lesioned and intact sides. This asymmetry most probably causes the static and dynamic vestibular deficits observed in the acute stage. After ∼50 h, the deafferented vestibular neurons recover a quasi‐normal resting activity which is thought to be the key of the compensation of the static vestibular syndromes. However, the molecular mechanisms underlying this recovery are unknown. In this study, we investigate possible changes in the distribution of glutamatergicN‐methyl‐d‐aspartate (NMDA) and glutamate metabotropic receptors and of glutamate decarboxylase 67k (GAD 67k) mRNAs in the deafferented vestibular neurons induced by the labyrinthine lesion. Specific radioactive oligonucleotides were used to probe sections of rat vestibular nuclei according toin situhybridization methods. Animals were killed at different times (5 h, 3 days and 3 weeks) following the lesion. Signal was detected by means of film or emulsion autoradiography. In the normal animals, several brainstem regions including the medial, lateral, inferior and superior vestibular nuclei were densely labelled by the antisense oligonucleotide NMDAR1 probe. However, the vestibular nuclei were not labelled by the glutamate metabotropic oligonucleotide antisense probe (mGluR 1). The GAD 67k antisense oligonucleotide probe labelled numerous small‐ to medium‐sized central vestibular neurons but not the larger cell bodies in the lateral vestibular nucleus. This agrees with previous studies. In the hemilabyrinthectomized rats, no asymmetry could be detected, at either the autoradiographic or cellular levels, between the two medial vestibular nuclei whatever the probe used and whatever the delay following the lesion. However, for the NMDAR1 probe, the mean density of silver grains in both the deafferented and intact medial vestibular neurons was 20% lower 5 h after the lesion. Three days and 3 weeks later, the intensity of labelling over all cells was the same as in the control group. Further studies are necessary to confirm the relatively weak modification of the NMDAR1 mRNAs expression and to exclude a change of GAD 65 and of other NMDA subunit mRNAs during the vestibular com

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00301.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe mechanisms that lead ultimately to neuronal death in pathological ageing of the brain remain mostly unknown as in the case of Parkinson's disease where there is a progressive and selective loss of dopaminergic neurons within the substantia nigra. Dopamine‐expressing PC12 cells that were neuronally differentiated by nerve growth factor treatment were chosen as a culture model in which to study some of the changes that may occur during the course of the degenerative process. They were exposed to the calcium ionophore A23187 in order to produce a sustained rise in cytoplasmic calcium, a phenomenon related to various pathological conditions. The degenerative effects of the ionophore were dose‐ and time‐dependent. They were characterized by early fragmentation of the neurites followed ultimately by a loss in cell viability. Biochemical changes, such as a decrease in [3H]dopamine uptake and modulations of the tyrosine hydroxylase gene, were detected before macroscopic evidence of cell suffering (e.g. neurite fragmentation) could be observed. Although an ongoing degenerative process was occurring in cell somata, PC12 cells were able to recover upon ionophore withdrawal. Characteristics of apoptosis such as chromatin condensation and DNA fragmentation were detectable in a small population of dying cells. DNA fragmentation could be prevented by the endonuclease inhibitor aurintricarboxylic acid. New protein synthesis was not required, as cycloheximide failed to prevent degeneration. Taken together, these results suggest that differentiated PC12 cells react to calcium stress through a sequence of regulatory processes which appears to be independent of the apoptotic pa

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00302.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe rat brain‐derived neurotrophic factor (BDNF) gene consists of four short 5‐exons linked to separate promoters and one 3′‐exon encoding the mature BDNF protein. Usingin situhybridization we demonstrate here that kindling‐induced seizures, cerebral ischaemia and insulin‐induced hypoglycaemic coma increase BDNF mRNA levels through insult‐ and region‐specific usage of three promoters within the BDNF gene. Both brief (2 min) and longer (10 min) periods of forebrain ischaemia induced significant and major increases only of exon III mRNA in the dentate gyrus. Following hypoglycaemic coma (1 and 30 min), exon III mRNA was markedly elevated in the dentate gyrus and, in addition, exon I mRNA showed a moderate increase. Single and recurrent(n= 40) hippocampal seizures significantly increased expression of exon I, II and III mRNAs in the dentate gyrus granule cells. After recurrent seizures, including generalized convulsions, there were also major increases of both exon I and III mRNAs in the CA3 region, amygdala, piriform cortex and neocortex, whereas in the hippocampal CA1 sector marked elevations were detected only for exon III mRNA. The insults had no effect on the level of exon IV mRNA in the brain. The region‐ and insult‐specific pattern of promoter activation might be of importance for the effectiveness of protective responses as well as for the regulation of plastic changes foll

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00303.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY