摘要:

AbstractTwo oligodendrocyte membrane proteins, NI‐35 and NI‐250, have been shown to be highly inhibitory for neurite growth. Upon neutralization of these components with the specific monoclonal antibody IN‐1, lesioned corticospinal tract fibres were able to regenerate over long distances. In the present study, we have investigated the behaviour of regenerating cholinergic septohippocampal tract fibres. Large fimbria/fornix aspiration lesions were bridged by human amnion extracellular matrix material containing nerve growth factor, and the inhibitor‐neutralizing antibody IN‐1 or a control antibody were applied. After 3–5 weeks survival time, acetylcholinesterase (AchE)‐positive fibres had crossed the bridge and, upon entering the hippocampus, had developed a profuse fibre plexus. In the controls (antibody against peroxidase) the fibre growth within the hippocampal tissue remained limited to maximally 1 mm in the caudal and lateral directions. In the presence of the antibody IN‐1, however, AchE‐positive fibres were seen to grow for 2–4 mm both in the caudal and lateral directions. Interestingly, the regenerated fibres preferably grew to their original terminal areas in the infra‐ and suprapyramidal layers of the hippocampus proper and the hilus, and in the supragranular layer of the dentate gyrus. These data show that the neurite growth inhibitors severely impede regenerative axon growth also for the cholinergic fibres in the hippocampus, and that their neutralization increases axon growth and leads to partial reconstitution of the original anatomic

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00093.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractIn a battery of four acute and chronic nociceptive tests, the GABA antagonist picrotoxin produces a uniform and sustained analgesia in mice. By contrast, barbiturates which have been presumed to act at the same receptor produce mixed and paradoxical actions. At a standard time of 10 min after drug administration a convulsant barbiturate [5‐ethyl‐5‐(3′‐rnethyI‐but‐2′‐enyl)‐barbituric acid] produced analgesia in three tests but had no effect in the fourth; a pure hypnotic barbiturate (amylobarbitone) produced hyperalgesia in three tests but analgesia in the fourth; while the mixed hypnotic‐convulsant pentobarbitone produced hyperalgesia in two of the tests and was without any effect in the other two. There was no pattern in these results with respect to acute or chronic nociceptive tests. Surprisingly, with extended observation using the tail‐flick test both pentobarbitone and the pure hypnotic (amylobarbitone) gave early hyperalgesia followed by analgesia; the convulsant barbiturate gave only analgesia. The results suggest a role for GABAAreceptors in the transmission of nociceptive information; they also suggest that barbiturates act at qui

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00094.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractCalbindin‐28K (CaBP) is a calcium‐binding protein widely distributed in the brain. This protein appears to be involved in the sequestration and the translocation of intracellular free calcium. In this study, we have examined the distribution pattern of the structures immunoreactive for CaBP in the hippocampal formation from slices of young (4 months) and aged (24–27 months) rats previously submitted to electrophysiological measurements. We demonstrated a marked loss in the number of pyramidal cells immunoreactive for CaBP in aged rats as compared to young rats. A consistent decrease in the staining intensity was also revealed by optical density measurements. Some experiments have suggested that calcium homeostasis is modified in hippocampal neurons of aged rats. The loss of CaBP‐like immunoreactivity (CaBP‐LI) labelling could result from an increase in intracellular calcium concentrations. To support this hypothesis, we showed that in young rats (i) the CaBP‐LI was enhanced in pyramidal neurons when the slice was preincubated in a calcium‐free medium, and (ii) CaBP‐LI was strongly decreased when the slice was preincubated in a high‐calcium medium (5 mM) and when the entry of calcium into the cell was increased by a short application of an excitatory amino acid in the medium. Our results suggest that the loss of CaBP‐LI in the hippocampus of aged rats could be due to an increase in intracellular calcium concentration. Preliminary observations of hippocampal slices at different times after induction of long‐term potentiation (LTP) failed to show significant changes in CaBP immunoreactivity, suggesting that this calcium‐binding protein is not directly in

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00095.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractHippocampal slices from guinea‐pigs were used to examine the long‐term potentiation (LTP) of theN‐methyl‐D‐aspartate (NMDA)‐mediated excitatory postsynaptic potential (EPSP). lntracellular recordings were performed from CA1 pyramidal neurons in the presence of 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX, 5–10 μM) and picrotoxin (50 μM). In these experimental conditions test stimuli applied at low frequency (0.1 Hz) to the Schaffer collateral ‐ commissural pathway evoked a prolonged EPSP (150–200 ms). To obtain this CNQX‐resistant EPSP, stimulus intensities had to be raised above the level required to evoke an EPSP of comparable amplitude in physiological solution. Tetanic stimulation (two trains of 100 Hz, 1 s every 20 s) led to a potentiation of the CNQX‐resistant EPSP, and this potentiated response was abolished withd‐(‐)‐2‐amino‐5‐phosphonovaleric acid (50μM). The potentiation of the NMDA receptor‐mediated EPSP was more pronounced for strong than for weak test stimuli, and was suppressed when test EPSPs were evoked during membrane hyperpolarization. These results suggest that NMDA receptor‐mediated responses can undergo LTP,

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00096.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractThe development of the major morphological and electrophysiological properties of presumptive Purkinje cells (PCs) was studied in primary cultures of rat cerebellum dissociated on the 14th embryonic day, when PCs are minimally differentiated and migratein vivoPCs were identified with a specific antibody to calbindin D‐28K (CaBP), which allowed visualization of the different morphological types of PCs between 3 and 29 daysin vitro(DIV). CaBP‐immunopositive cells were first detected at 3 DIV. Thereafter, the shape of these cells resembled some of those describedin vivaAfter 20 DIV, 95% of the CaBP‐immunopositive cells had characteristic PC dendritic trees, although they were very atrophic. Glial cells immunopositive for the glial fibrillary acidic protein (GFAP) were first seen at 3 DIV. Thereafter GFAP‐immunopositive cells resembled Bergmann cells or velate astrocytes. Neurons regarded as PCs were studied electrophysiologically using the patch‐clamp whole‐cell configuration. Voltage‐dependent, tetrodotoxin‐sensitive fast inward currents were virtually absent at 2–4 DIV, but increased between 7 and 14 DIV to reach two‐thirds of the amplitude obtained after 15 DIV. These currents were large enough to give rise to overshooting spikes as early as 7 DIV in the current‐clamp mode. This time schedule is in keeping with that of PCs developedin situ.The tetraethylammonium‐sensitive, slowly inactivating outward currents had reached two‐thirds of the amplitude obtained after 15 DIV by 3–4 DIV. Their amplitude remained stable between 4 and 7 DIV, and increased to their maximal value during 7–14 DIV, with a marked shortening of action potentials. 4‐Aminopyridine‐sensitive, fast‐inactivating outward currents might also be associated with development, since they were present in 66% of the cells between 7 and 14 DIV but in only 39% from 15 to 29 DIV; however, their amplitude did not vary with time. Presumptive PCs borel‐glutamate‐activated receptors, which preceded the emergence of kynurenate‐sensitive, spontaneous synaptic currents at 7 DIV. These currents were sometimes intermingled with inhibitory currents, although presumptive PCs were sensitive to γ‐aminobutyrate at 7 DIV. The present model represents some unequivocal features of PC development, although the PCs used had undergone minimal differentiationin vivoand were cultu

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00097.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractThe origin and the topographic distribution of corticorubral (CR) projections in the guinea‐pig were studied by using the retrograde axonal transport of a tracer, colloidal gold‐labelled, enzymatically inactive horseradish peroxidase conjugated to wheat‐germ agglutinin (WGAapoHRP‐Au), which was injected in the red nucleus (RN). It was found that the bulk of the CR projections arise from layer V neurons of the agranular frontal cortex in both its medial (Agm) and lateral (Agl) subdivisions; in the Agm labelled neurons are preferentially located in the upper part of layer V, whereas in the Agl they are more concentrated in the central band of the layer. Fewer projections originate from areas of the granular parietal and the agranular cingulate and retrobulbar cortices. CR projections have a bilateral origin, with a large ipsilateral predominance. The pattern of retrograde cortical labelling observed after injection of WGAapoHRP‐Au in different portions of the RN indicates that CR projections are distributed throughout the entire rostrocaudal extent of the nucleus, but are slightly more concentrated in the rostral parvocellular area. The morphological arrangement of CR projections in the guinea‐pig, as demonstrated in the present study, shows several analogies with other mammals. The functional characteristics of the cortical areas in which CR neurons are located indicate that CR projections may play a significant role in the central organization

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00098.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractThe discovery of molecular markers which are selectively expressed during the development of specific classes of rat central nervous system macroglia has greatly advanced our understanding of how these cells are related. In particular, it has been shown in tissue culture that oligodendrocytes and some astrocytes (type‐2) may be derived from a common progenitor cell (O‐2A progenitor). However, the existence of type‐2 astrocytesin vivohas yet to be unequivocally established. Recently, it has been reported that the neural‐specific growth‐associated protein‐43 (GAP‐43, otherwise known as 8–50, F1, pp46 and neuromodulin) may be expressed by cells of the O‐2A lineagein vitro.We set out to examine the cellular specificity of GAP‐43 in O‐2A progenitors and their descendantsin vitroandin vivo.Using a polyclonal antiserum against a GAP‐43 fusion protein we have shown the presence of immunoreactive GAP‐43 in the membranes of bipotential O‐2A glial progenitor cells and type‐2 astrocytes by Western blotting and immunocytochemistry of cells in culture. In contrast to previous studies, double labelling with mature oligodendrocyte markers showed that GAP‐43 is down‐regulated during oligodendrocyte differentiationin vitro.Immunohistochemical staining of sections of developing rat brain demonstrated the same developmental regulation of GAP‐43, suggesting that oligodendrocytes only express GAP‐43 at immature stages. In addition, normal and reactive astrocytes in tissue s

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00099.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractImmunocytochemical localization of a product of the proto‐oncogene c‐fos, Fos protein, was used to map the activity of a subset of rat spinal neurons at 3 days, 3 weeks and 3 months following section of the sciatic nerve. In a well‐established experimental paradigm, the gene was induced by activation of primary afferent fibres with brief noxious sensory stimulation under anaesthetic. Central sciatic projections were demonstrated with isolectin B4counterstain and GAP43 immunocytochemistry. In Rexed's lamina II of the spinal cord, in which there is somatotopic organization of afferent terminals, Fos‐positive neurons were largely restricted to the projection area of intact peripheral nerves. Three days after a sciatic nerve lesion, the number of Fos‐positive neurons in a cord region innervated by the saphenous nerve was similar to control levels, but was markedly increased by 3 weeks, remaining elevated at 3 months. Three weeks after sciatic nerve section the lectin stain in the area of sciatic representation had almost completely disappeared, and conversely GAP43 staining had greatly intensified. There was no evidence of invasion by Fos‐immunoreactive cells of the area of sciatic representation. After 3 months both the size and the intensity of the lectin gap, and of the corresponding area of increased GAP43 immunoreactivity, appeared reduced. Thus a peripheral nerve lesion was followed by a delayed increase in excitability of the spinal cord as assessed by c‐fosexpression, so that greater numbers of second‐order neurons were activated by sensory stimulation of an adjacent intact nerve. These changes may be related to the sensory abnormalities which foll

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00100.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractThe mRNA distribution of chromogranins A and B and secretogranin II was determined in rat brain. In Northern blots the oligonucleotide probes used hybridized with single mRNA species of the expected sizes. With tissue hybridization the mRNA signals for these three proteins were found throughout the brain. However, each of the three messages had a distinct distribution, which was exemplified by the fact that in the various regions either all three proteins, a combination of two or only one of them were apparently synthesized. Significant levels of all three mRNAs were found in several regions of the hippocampus and of the amygdala, in some thalamic nuclei and in the pyriform cortex. On the other hand the subiculum contained only the message for chromogranin A, the granule cell layer of the cerebellum only that for chromogranin B, and in posterior intralaminar thalamic and medial geniculate nuclei and in the nucleus of the solitary tract only secretogranin II mRNA was found. The distinct distributions of mRNAs for the chromogranins in various brain regions support the concept that these proteins are propeptides giving rise to functionally active components.

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00101.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractRelease properties of intrahippocampal transplants of noradrenergic neurons were monitored by microdialysis in awake and halothane‐anaesthetized rats. Fetal locus coeruleus neurons were implanted as a cell suspension into hippocampi deprived of their innate noradrenalin (NA) innervation by intraventricular 6‐hydroxydopamine treatment. Dialysis probes of the loop type were implanted into the dorsal hippocampus 1 ‐2 days before each experiment, i.e. 7–11 months after grafting. Age‐matched intact and lesion‐only animals served as controls. Microscopic analysis showed a graft‐derived tyrosine hydroxylase immunoreactive, presumably noradrenergic, fibre network throughout the dorsal hippocampal formation, surrounding the probe site. The innervation density varied from sub‐ to supranormal. The grafts restored baseline NA release in the graft‐reinnervated hippocampus to near‐normal levels both in awake and halothane‐anaesthetized animals. Potassium chloride (100 mM) in the perfusion fluid induced a dramatic increase in NA release that was similar in magnitude in the grafted and intact hippocampi. A NA uptake blocker (desipramine) added to the perfusion fluid at 5 μM induced a similar increase in NA output in the grafted and intact hippocampi, and the output was substantially reduced by tetrodotoxin, added at 1 μM in the presence of uptake blockade. Electrical stimulation of the lateral habenular nucleus (15 Hz, 0.5 mA) in halothane‐anaesthetized rats induced a significant increase in NA output both in the intact and grafted hippocampi. This effect was abolished by transection of the fasciculus retroflexus, which carries the efferent projections of the habenular complex. Behavioural activation through handling induced a consistent increase in NA release only in the intact animals, but in a few grafted rats (which also responded to habenular stimulation) the NA output was clearly elevated by handling. Forced immobilization induced a significant increase in NA output both in the intact and grafted hippocampi, but in the grafted ones the response was somewhat smaller and more transient. In the same set of animals, swimming in warm water (25–30°C) induced a sharp increase in NA output in the intact animals, whereas only one of the grafted rats responded by increased NA output. The results indicate that the locus coeruleus grafts, despite their ectopic location, can become functionally integrated with the host brain, and that the activity of the transplanted noradrenergic neurons can, under some circumstances, be modulated from the host brain in response

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00102.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY