摘要:

AbstractChronic enhancement of neuromuscular activity by forced exercise training programmes results in selective adaptation of the G4acetylcholinesterase (AChE) molecular form in hindlimb fast muscles of the rat, with only minor and non‐selective AChE changes in the soleus. In order to shed further light on the physiological significance of this G4adaptation to training, we turned to a voluntary exercise model. The impact of 5 days and 4 weeks of voluntary wheel cage running on AChE molecular forms was examined in four hindlimb fast muscles and the slow‐twitch soleus from two rat strains. Inbred Fisher and Sprague– Dawley rats, placed in live‐in wheel cages, exercised spontaneously for distances which progressively increased up to an average of ∼3 and 18 km/day, respectively, by the end of week 4. Fast muscles responded to this voluntary activity by massive G4increases (up to 420%) with almost no changes in A12, so that by week 4 the tetramer became the main AChE component of these muscles. The additional G4was composed primarily of amphiphilic molecules, suggesting a membrane‐bound state. The G4content of fast muscles was highly correlated with the distance covered by the rats during the 5 days before they were killed (r= 0.850‐0.879,P<0.001 in three muscles). The soleus muscle, in turn, responded to wheel cage activity by a marked selective reduction of its asymmetric forms—up to 45% for A12. This A12decline, already maximal by day 5 of wheel cage running, showed no relationship with the distance covered. The present results constitute strong new evidence suggesting that the role of AChE in neuromuscular transmission is not limited solely to the rapid inactivation of just‐relea

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00979.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractUsing immunohistochemical techniques we have analysed the occurrence of cholecystokinin‐like immunoreactivity (CCK‐LI) in the cortex and striatum of the rat. In the cortex few CCK‐immunoreactive cell bodies, mainly interneurons, could be visualized in normal brains, and a moderately dense network of CCK fibres was also observed. Injections of colchicine into the striatum led to an accumulation, in the surrounding cortex, of CCK‐LI in the initial segment of the axon of numerous cells. In addition, with an antibody to pro‐CCK several cell bodies, many of which with pyramidal shape, could be visualized. Furthermore, retrograde staining of cortical cells after unilateral injection of wheat germ agglutinin into the striatum revealed bilaterally in the cortex a number of labelled cells that also contained pro‐CCK‐LI. In the striatum CCK‐LI was diffusely distributed in fine fibres as well as in patches of fibres located in the medial aspects. After decortication followed by callosotomy these patches disappeared on the side ipsilateral to the lesion, while the pattern of immunoreactivity of several other peptides in the striatum was unaffected. No change was observed on the contralateral side. Decortication or callosotomy alone did not affect the pattern of CCK‐LI. At the ultrastructural level several CCK‐immunoreactive terminals could be observed, mostly with clear, densely packed vesicles and straight asymmetric synaptic contacts with small spines, characteristic for terminals of cortical origin. The results are consistent with the presence of a major, partly crossed, CCK‐containing cor

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00980.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractUntil recently, astrocytes were not considered as sites for neurotrophic factor action. We show here that, bothin vivoandin vitro, astrocytes express receptors for two separate families of neurotrophic factors. In the intact adult rat CNS, astrocytes express the extracellular domain of the neurotrophin receptor TrkB and, in a more restricted population, the low‐affinity nerve growth factor receptor p75LNGFR. In the lesioned CNS, expression of the alpha component of the receptor for ciliary neurotrophic factor (CNTFRα) switches from a purely neuronal localization to cells in the glial scar at the edge of the wound. Using cultured hippocampal astrocytes as a model to address the functional status of these receptors, we have found only the truncated forms of TrkB and TrkC, which are incapable of signal transduction as measured by protein tyrosine phosphorylation or immediate early gene induction. In contrast, a fully functional CNTF receptor complex capable of signal transduction is present on cultured astrocytes. Thus, the neurotrophin receptors may act primarily to sequester or present the neurotrophins, whereas in the case of CNTF a functional response can be initiated within the astrocy

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00981.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractIn the present work we have characterized a possible mechanism leading to the early survival of neostriatal cholinergic neurons after quinolinic acid injection. Different doses of quinolinic acid were injected in rat neostriatum and two different parameters were analysed 7 days after the lesion: choline acetyltransferase (ChAT) activity and nerve growth factor (NGF) levels. We have observed that ChAT activity decreased (until 68 nmol quinolinic acid) and NGF levels increased (until 34 nmol quinolinic acid) in a dose‐dependent manner. In order to characterize the time‐course of the lesion on NGF levels and ChAT activity, and the possible protective effect of NGF and basic fibroblast growth factor (bFGF) on cholinergic neurons, we have used the quinolinic acid dose (68 nmol) at which the first decrease of ChAT activity was observed. ChAT activity and NGF levels showed different patterns of response to quinolinic acid injection, since the maximal effect was reached at 1 day for ChAT activity and at 2 days for NGF levels. NGF or bFGF simultaneously injected with quinolinic acid (68 nmol) completely prevented the decrease in ChAT activity in a dose‐dependent manner but NGF was more effective than bFGF. Furthermore, differences observed in ChAT activity after NGF but not bFGF treatment were correlated with changes in the number of ChAT immunoreactive cells. Finally, we have also observed that, although bFGF alone was not able to modify NGF levels, bFGF simultaneously injected with quinolinic acid produced an increase of NGF levels higher than that observed after quinolinic acid injection alone. Our results show that NGF and bFGF protect striatal cholinergic neurons against quinolinic acid injury, and bFGF is able to potentiate the increase of NGF after the lesion, suggesting a cooperative action between different trophic factors in neuronal protection after excitotoxic injury. Thus, administration of trophic factors may be relevant in the prevention and treatment of neurodegenerative disorders, such as Huntington's di

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00982.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractLocal spinal cord lesions are often greatly enlarged by secondary damage, a process which leads to massive additional cell death. This process is poorly understood. In order to investigate which types of cells could play a role in increasing the size of the lesion, we have analysed the events occurring at rat spinal cord lesion sites from 1 h to 3 months after partial transection using cell type‐specific markers. One hour after transection, the lesion site was small and corresponded to the zone of primary mechanical damage. Extravasation of blood and an opening of the blood – brain barrier occurred. Rapidly thereafter, at 3 and 6 h, an area of secondary cell death developed around the zone of the primary lesion. This secondary cell death, which was probably largely of the necrotic type, affected neurons, macroglia and microglial cells indiscriminately. It was virtually complete at 12 h. Recruitment of inflammatory cells followed a time course which lagged behind that of secondary cell death. Adhesion of neutrophils to the inside of blood vessels was observed at 3 h. They appeared in large numbers at 6 h at the site of the primary lesion, but not yet in the area of secondary cell death. They were numerous throughout the lesion site at 24 h and then disappeared rapidly. Proliferation and recruitment of macrophages and microglial cells became predominant 2 days after injury. Their density was highest within the lesion site between 4 and 8 days. Very few astrocytes were present in the lesion site during the first week. In contrast, the surrounding area contained numerous activated astrocytes, which began to delineate the lesion site. After 2 weeks, the microglial cells and macrophages progressively disappeared from the lesion site, and a cavity formed. A glial scar surrounded this cavity and consisted of reactive astrocytes and activated microglial cells. The time course of the cellular reactions observed here suggests that secondary damage is not primarily due to destructive effects of neutrophils and macrophages. The inflammatory process after spinal cord transection is qualitatively similar to that observed outside the CNS. Inflammatory cells, which can release cytokines and growth factors, could play important roles in protective reactions of the tissue and glial scar format

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00983.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe human extrastriate occipital cortex contains several visual areas that are probably analogues of macaque areas V2, V3, VP, V4 and V5. Tracing of callosal connections has led to the anatomical identification of these areas and to the characterization of some of them by cyto‐ and myeloarchitecture (Clarke and Miklossy, 1990). The pattern of cytochrome oxidase activity in these visual areas is now described in a normal case and in a case of age‐related bilateral macular degeneration. In normal cortex, the laminar distribution of cytochrome oxidase activity was similar in V2, V3, VP, V4 and V5; a prominent dark band covered most of layers III and IV, and its upper and lower limits were gradual. In V2, V3, V4 and V5 but not VP, layer II tended to be darker than the infragranular layers. The overall intensity of the staining varied between areas: VP was very light, V2, V3 and V4 were darker, and V5 was very dark. A different, two‐band pattern of cytochrome oxidase activity was found in a restricted region of the posterosuperior precuneus. The bilateral age‐related macular degeneration had led to a great loss of ganglion cells in the central, but not in the peripheral retinae. The central representation in the lateral geniculate nuclei showed abnormally weak staining for cytochrome oxidase, particularly in the parvocellular layers. In the cortex, the contrast between lightly and darkly stained regions was greater than in the normal case. In particular, V5 was very heavily stained, and in V1 and V2 there were two different types of dark stripes that may represent compartments driven predominantly by the magnocellular

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00984.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractWe have previously shown that the enzyme choline‐O‐acetyltransferase (ChAT) exists in a hydrophilic and an amphiphilic form inDrosophilahead. A complementary DNA clone of 4.2 kb containing the entire coding region of ChAT was isolated from a cDNA library ofDrosophilaheads. The cDNA was subcloned in an expression vector and injected into the nucleus ofXenopusoocytes. Injected oocytes expressed high levels of ChAT activity. This activity was inhibited by bromoacetylcholine, a specific inhibitor of the enzyme. In the present study the non‐ionic detergent Triton X‐114 was used to analyse whether the expression of hydrophilic and amphiphilic ChAT was or was not directed by a single cDNA. The two forms of ChAT were found to be synthesized in injected oocytes. Approximately 9% of the recombinant enzyme partitioned as amphiphilic activity. This value was similar to that found for native amphiphilic ChAT inDrosophilaheads. Sedimentation in sucrose gradients of amphiphilic enzyme was found to be influenced by the type of detergent present in the gradient whereas this was not the case for hydrophilic ChAT. Hydrophilic and amphiphilic enzyme activities differed in some of their biochemical properties. Amphiphilic ChAT was less sensitive to inhibition by the product acetylcholine than was hydrophilic ChAT. Moreover, amphiphilic ChAT was found to be more resistant than hydrophilic ChAT to heat inactivation at 45°C. These properties were observed for the native as well as for recombinant ChAT. These results demonstrate that the hydrophilic and amphiphilic forms of ChAT are derived from

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00985.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe long‐term behavioural effects of prenatal chronic anaemic hypoxia were investigated in young (5 months old), late adult (19 months) and aged Wistar rats (23–26 months). Sodium nitrite (2 g/l) offered in the drinking water during the second half of pregnancy served to evoke prenatal hypoxia. In parallel to nitrite treatment the Ca2+channel blocker nimodipine (10 mg/kg) or vehicle alone was administered intragastrically once daily. Open‐field activity, intermale social behaviour, learning ability in a black–white discrimination paradigm and fear‐induced emotionality were assessed at different ages. Plasma corticosterone response to novelty stress was measured by blood sampling through chronic venous canulas at the age of 28 months. The nitrite‐exposed 5‐month‐old offspring started exploration in a novel open‐field with considerable delay. This delayed start‐latency was augmented in 19‐ and 23‐month‐old rats, pointing to exaggerated suppression of behavioural arousal. Nitrite‐induced hypoxia decreased the duration of social interactions during ageing. Aged rats exposed to nitrite were unable to learn a black–white discrimination but showed a normal generalized conditioned fear response (immobility) to the test situation as a whole. The conditioned fear‐induced vocalization was more frequent among hypoxic aged animals. The aged hypoxic rats displayed a prolonged plasma corticosterone stress response and had higher adrenal weight than their controls. The abnormal open‐field, social, learning and emotional behaviours, as well as the altered plasma corticosterone response, were prevented

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00986.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractGrowth‐associated protein‐43 (GAP‐43) and synapsin were used as molecular markers for synaptic reorganization in the adult cat visual system following sensory deprivation. Small binocular retinal lesions (central 10°) were made with a xenon light photocoagulator in adult cats. One, 3, 5 and 7 weeks after induction of the lesion, the neuropil levels of synapsin and GAP‐43 in the dorsal lateral geniculate nucleus (dLGN) and area 17 were determined by immunocytochemistry. GAP‐43 displayed a moderately low basal level in the dLGN of normal adult cats. The parvocellular C layers and the interlaminar plexi were characterized by higher immunoreactivity for GAP‐43. Lesion‐induced alterations were observed in all layers: GAP‐43 immunoreactivity increased in the part of the dLGN representing central vision. This increase was maximal 3 weeks after the lesion. Under our experimental conditions, sensory deprivation did not significantly alter GAP‐43 levels in the visual cortex. The changes in synapsin immunoreactivity were also restricted to the dLGN. In this nucleus, synapsin immunoreactivity decreased in all layers in the part subserving central vision 1 week after lesion. By 3 weeks after lesion, the level of synapsin had already returned to normal. This study provides evidence for a capacity for structural remodelling in primary sensory brain areas such as the dLGN throughout adult life. The observed changes in GAP‐43 and synapsin in the dLGN suggest that synaptic reorganization is induced by retinal lesions. Normalization of synaptic density and activity could be important for the survival of the partially deafferente

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00987.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe beta transforming growth factors (TGF‐β) are suggested to regulate developmental processes since they are distinctly expressed during embryogenesis and exert pleiotropic effects on cell growth and differentiation. In the present study the expression of TGF‐β isoforms was investigated in the postnatal and adult mouse brain. As shown byin situhybridization, TGF‐β2was expressed in the choroid plexus, hippocampus, dentate gyrus and cerebellar Purkinje neurons, both postnatally and in adults. Furthermore, TGF‐β2expression was observed postnatally in immature cerebellar neurons of both the external and internal granule cell layers. In the external granule cell layer, the frequency of TGF‐β2transcripts increased until postnatal day 10 and declined thereafter. In contrast to TGF‐β2, no TGF‐β1mRNA was detected in cerebellar granule cells. TGF‐β3expression was widely distributed in postnatal brains although at very low levels. The significance of TGF‐β2production by cerebellar granule cells was further investigated using cultures of small cerebellar neurons. In these cultures reverse polymerase chain reaction analysis revealed expression of TGF‐β2but low or almost undetectable levels of TGF‐β1or ‐β3mRNAs. Likewise, only TGF‐β2protein in its latent form was identified in the culture supernatant; the release of TGF‐β2was maximal during the second dayin vitro.Furthermore, TGF‐β was found to inhibit the proliferation of cultured small cerebellar neurons. Taken together, these data suggest that TGF‐β2is involved in the regula

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00988.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY