摘要:

WE have recently shown that long-term, but not acute, treatment with lithium robustly protects cultured CNS neurons against excitotoxicity mediated by NMDA receptors. Since NMDA receptor over-excitation has been strongly implicated in the ischemic brain injury, we examined the effects of chronic lithium treatment on neurological deficit and brain infarct induced by occlusion of the left middle cerebral artery in rats. Subcutaneous injection of LiCl for 16 days significantly improved neurological deficits, including abnormal posture and hemiplegia, measured 24 h after artery occlusion. Importantly, the size of ischemic infarct was reduced by 56% after lithium pretreatment. These results raise the possibility that lithium may be useful for reducing focal ischemia-induced brain damage and neurological abnormalities.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

IN order to examine the relationship between long-term potentiation (LTP) and phosphoinositide (PI) turnover, we evaluated these throughout anesthetized rat brain using carbon-11-labeled diacylglycerol (11C-DAG). High-frequency tetanic stimulation (400 pulses at 40 0Hz) to the perforant pathway induced LTP in rat dentate gyrus. In autoradiograms of rat brains, LTP was associated with the occurrence of multiple highly radioactive spots in many regions distant from the stimulated site. Following i.v. administration of an NMDA receptor antagonist prior to stimulation, however, no high-density spots were found. These findings directly demonstrate that potentiation of phosphoinositide-derived signaling was induced during LTP, and the finding of multiple location suggests the occurrence of polysynaptic neurotransmission through neural networks pertaining to learning and memory.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

INCUBATION of cultured hippocampal slices with chloroquine, a compound that increases the pH of acidic subcellular organelles, for 1 0 h reduced the activity of cathepsin L by 8 3 ± 0.87% (mea n ± s.e.m.) while only marginally suppressing cathepsin B. This effect was followed within 3 h by an increase in the concentration of mature, single-chain cathepsin D (up 6 1 ± 28%). Selective depression of cathepsin L with N-CBZ L-phenylalanyl-L-phenylalanine-diazomethylketone also resulted in increases in enzymatically active cathepsin D and the delayed appearance of a 2 9 kDa fragment of the tau protein. These findings demonstrate that the pattern of cathepsin L, B, and D changes found in the aged brain can be reproduced by reducing the acidity of the lysosomal milieu. They also indicate that such pH shifts initiate a sequence of linked disturbances (inactivation of cathepsin L >induction of cathepsin D >aberrant tau proteolysis) likely to play an important role in brain ageing.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

SINCE the characterization of orphanin FQ (OFQ), the endogenous ligand of ORL1 receptor, much work has focused on its physiological functions. OFQ was reported to antagonize the effect of opioid-induced antinociception, although its mechanism remains obscure. In the present study, whole-cell patch clamp recording technique was used to observe if OFQ can reverse the inhibition of calcium current produced by the κ-opioid agonist U50,488H (U50) in acutely dissociated rat DRG neurons. The concentrations of OFQ and U50 were 50 nM and 10 μM, respectively. Among 49 cells recorded, the calcium channel currents of 37 (75.5%) cells were inhibited by U50, of which 30 (81.1%) cells could be reversed by OFQ. It was interesting to note the similarity between OFQ and the well characterized anti-opioid peptide CCK-8 in that it reversed κ-opioid receptor agonist induced suppression on calcium channel current, while by itself showed a calcium channel suppressive effect. Thus OFQ may be regarded as another anti-opioid peptide.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

TRANSGENIC mice expressing antisense directed against glucocorticoid receptor (GR) mRNA were used for a longitudinal study on the effects of hypothalamic-pituitary-adrenocortical dysfunction on anxiety-related behaviour and locomotor activity. Compared with age-matched controls and 5-week-old transgenic animals, 13- and 36-week-old transgenic mice made significantly more entries into and spent significantly more time on the open arms of the elevated plus-maze thereby indicating reduced basal anxiety. In contrast, time spent in the central area of the open field was significantly reduced in transgenic animals indicating an enhanced anxiety under conditions of increased stress. Locomotor activity did not differ between transgenic and control animals. Our results indicate that behavioural changes in transgenic mice differ according to the age of the animals and the behavioural paradigm used. Transgenic animals with an impaired GR function may be of help in studying the interaction of ageing, GR function and the development of behavioural abnormalities.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

PREVIOUS studies have reported that some patients with damage to striate cortex retain the ability to detect monochromatic light and discriminate direction of achromatic movement in their blind visual fields. We investigated the residual chromatic visual capacity of a well-studied patient (GY) who has a unilateral lesion to striate cortex (V1). The data demonstrated that GY was able to detect and discriminate isoluminant colour targets presented in his blind hemifield. The velocity and contrast of chromatic moving stimuli affected GY's levels of conscious experience of movements he was able to discriminate. As the velocity or contrast was increased, his discrimination performance improved in line with rising visual awareness and judgement confidence. At isoluminance, GY continued to discriminate motion direction with above chance accuracy. These results indicate chromatic signals can also be used to process motion information in the absence of primary visual cortex.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

GUINEA-PIGS were exposed to a traumatic sound inducing up to &THgr; dB hearing loss. Beside the well described mechanical damage to outer hair cells, a total disruption of inner hair cell (IHC)–auditory nerve synapses was acutely observed within the traumatized area. To test the hypothesis that synaptic damage is due to an excessive release of glutamate by the IHCs, we examined the protective effect of the glutamate antagonist kynurenate on noise-induced hearing loss. The high degree of protection observed with kynurenate attests that dendritic damage is an important component in noise-induced hearing loss. Moreover, we demonstrate that a synaptic repair mechanism occurring within the first few days post-exposure is partly responsible for the recovery of temporary threshold shifts after an acoustic trauma.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

POSITRON emission tomography (PET) was used in a cross-linguistic study to compare pitch processing in native speakers of English, a nontone language, with those of Thai, a tone language. When discriminating pitch patterns in Thai words, only the Thai subjects showed activation in the left frontal operculum. Activation of this region near the classically defined Broca's area suggests that the brain recognizes functional properties, rather than simply acoustic properties, of complex auditory cues in accessing language-specific mechanisms in pitch perception.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

RECENT studies have begun to elucidate the localization of ion channels and receptors in central nervous system synapses. A family of proteins containing PDZ domains has been suggested to play essential roles in these processes. PSD-95 and chapsyn-110 have been implicated in the clustering of Shaker K+channels and NMDA receptors in the mammalian brain, and Dlg plays a role in the clustering of Shaker K+channels at the Drosophila neuromuscular junction (NMJ). We have explored whether Dlg might participate in mammalian NMJ organization. We demonstrate that Dlg is expressed in muscle and co-localizes with utrophin at the post-synaptic face of the mammalian NMJ. Dlg may therefore be important for establishing or maintaining the organization of protein complexes at the mammalian NMJ.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BRAIN metabolites were measured by proton magnetic resonance spectroscopy in five young (4–10 years of age) and six old (24–30 years of age) adult rhesus monkeys. The two age groups had similar levels of N-acetylaspar-tate and of choline relative to creatine, but the ratio of myo-inositol/creatine was higher in each old monkey than in any of the young animals. There was no significant relationship between the metabolite ratios and cognitive performance. The findings indicate that a consistent pattern of non-invasively detectable biochemical changes occurs in the brain with ageing. Whether these changes have functional significance in age-related pathologies, or are simply markers of brain ageing will be the subject of future studies.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID