摘要:

INCREASED glutamate or acetylcholine receptor stimulation may interact with mitochondrial failure to increase the vulnerability of cholinergic neurons within the nucleus basalis. Understanding of the mechanisms that underlie this vulnerability may lead to a therapy to prevent the degeneration of these neurons in Alzheimer's disease. In the presence of a mitochondrial energy deficit, excess stimulation ofN-methyl-D-aspartate (NMDA) receptors was not required for cytotoxicity. Furthermore, stimulation of cholinergic receptors was cytotoxic to cholinergic neurons but this toxicity was not enhanced by NMDA stimulation. Chronic administration of NMDA antagonists, such as meniantine, amantadine or MK-801, attenuated the effects of mitochondrial failure in the presence or absence of excessive cholinergic or NMDA receptor stimulation.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The behavioural effects of m-chlorophenylpiperazine (mCPP) in rats and its clinical effects in man are thought to be related to its action at 5-HT2B/2Creceptors. However, although mCPP is a partial agonist at these subtypes in rat, its efficacy at human 5-HT2B/2Creceptors is unknown. We therefore investigated the activity of mCPP at cloned human 5-HT2Band 5-HT2Creceptors. mCPP was a partial agonist at the human 5-HT2Creceptor but antagonized the human 5-HT2Breceptor. Therefore, while supporting the proposal that at least some of the clinical effects of mCPP are likely to be mediated via stimulation of the 5-HT2Creceptor, this study also suggests that any 5-HT2Breceptor-mediated effects are more likely to result from receptor blockade than from receptor activation.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

THE neuroprotective activity of basic fibroblast growth factor (bFGF) in combination with theN-methyl-D-aspartate (NMDA) receptor antagonist MK-801 was evaluated in organotypic hippocampal slice cultures. Oxygen/glucose deprivation produced neuronal damage which was assessed using propidium iodide fluorescence. Treatment with increasing doses of bFGF demonstrated significant neuroprotection that was optimal at 10 ng ml−1. This effect was diminished at higher concentrations. MK-801, at the optimal concentration of 30 μM, demonstrated greater neuroprotective efficacy than bFGF. However, bFGF significantly enhanced the protection conferred by MK-801 alone. These results suggest that neurotrophic factors such as bFGF may augment the neuroprotective effects of NMDA antagonists against ischemic neuronal injury.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

INTERLEUKIN-1β (IL-1β) converting enzyme (ICE) cleaves pro-IL-1β to produce mature IL-β, and is a member of a family of proteases implicated in apoptosis. Intracerebroventricular (i.c.v.) administration of an irreversible ICE inhibitor, z-VAD-DCB (1 pmol, 30 min before and 15 min, 2, 4, 6 and 8 h after surgery) markedly reduced (50 ± 4%,p< 0.001) infarct volume measured 24 h after focal cerebral ischaemia (middle cerebral artery occlusion, MCAo) in the rat. Inhibition of damage was observed in the cortex (51 ± 5% reduction) and striatum (42 ± 6% reduction). These data implicate ICE in ischaemic neuronal deathin vivo. Inhibition of ICE could reduce ischaemic damage either by preventing IL- 1β synthesis or by inhibiting apoptosis or by both of these processes, and may provide a useful therapeutic approach to the inhibition of ischaemic brain damage.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

GROUP III metabotropic glutamate receptors (mGluR4, 6, 7, 8) are negatively coupled to adenylate cyclase and, when activated presynaptically, decrease the release of glutamate and GABA. We have used intracerebroven- tricular injections of agonists and antagonists believed to act selectively on these receptors to study the pro- or anti-convulsant effects of mGluR III activation in non- epileptic (Swiss-Webster) and epileptic (DBA/2) mice. In both mouse strains the prototypic agonists L-2-amino- 4-phosphonobutanoate (LAP4) and L-serine-O-phosphate are proconvulsant. The supposed antagonists (S)-2-methyl-2-amino-4-phosphonobutanoate (MAP4) and (RS)-α-methyl-4-phosphonophenylglycine (MPPG), have a predominantly proconvulsant effect. (S)-α- methyl-3-carboxyphenylalanine, which is a potent and selective antagonist for LAP4 in the cortex, is anticonvulsant in DBA/2 mice and decreases the convulsant effect ofN-methyl-D-aspartate, 3,5-dihydroxyphenyl- glycine, LAP4 and MPPG in Swiss-Webster mice. These data suggest that reduced inhibitory transmission may be more significant than reduced synaptic release of glutamate following group III mGluR activation.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

To clarify the cellular localization of neuropeptide-Y receptor subtypes in the dentate gyrus and CA3 sector of the rat dorsal hippocampus and their changes after kainic acid-induced seizures, we used receptor autoradiography to measure [125I]PYY binding to Y1and Y2receptors after colchicine treatment. Fifteen days after colchicine infusion in the dorsal hippocampus granule cells and their mossy fibres degenerated while the hilar interneurons and CA3 pyramidal cells were spared. This treatment markedly decreased [125I]PYY binding to Y1receptors in the molecular layer of the dentate gyrus (−82%) and in the hilus (−70%). [125I]PYY binding to Y2receptors was reduced by 40% and 48%, respectively, in the CA3 region and in the hilus. Thirty days after kainic acid treatment, [125I]PYY binding to Y1receptors was decreased by 35% in the molecular layer of the dentate gyrus whereas the binding to Y2receptors was increased by 116% in the hilus. The effect of colchicine in kainic acid-treated rats indicates that these plastic changes occur selectively on granule cell projections.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

N-methyl-D-aspartic acid (NMDA) was injected into the medial preoptic area (mPOA) of 10 rats to destroy the neurones in this region. Male sexual behaviour was scored before, and on days 2, 6, 10, 17, 24 and 31 after the administration of NMDA. The neurones in the injection site were destroyed in all the rats, but male sexual behaviour was only transiently reduced in the animals with lesions largely restricted to the mPOA. These findings are in contrast to the earlier reports of permanent suppression of sexual behaviour after electrolytic lesion, with damage to the neurones and fibres of passage. The present study shows that the mating behaviour could be expressed even after the destruction of the neurones in the mPOA.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

PERIPHERAL and central injections of recombinant rat interleukin-1β (IL-1β) have been shown to decrease social exploration in rats. To test the involvement of vagal afferents in the communication between the immune system and the brain, sham-operated and vagotomized rats were injected peripherally or centrally with physiological saline or IL-1β 4 weeks after surgery. Vagotomy attenuated the depression in social exploration induced by i.p. administration of IL-1β (15 μg) but did not alter the behaviour-depressing effects of an intracerebroventricular (i.c.v.) injection of IL-1β (45 ng). These results confirm the role of vagal afferent nerves in the transmission of an immune message from the periphery to the brain, and show that vagotomy does not impair the direct sensitivity of the brain itself to immune signals.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The aim of the present study was to determine whether administration of the synthetic ACTH-(4–9) analogue, Org 2766, directly into the ipsilateral vestibular nucleus complex (VNC), would enhance vestibular compensation following unilateral labyrinthectomy (UL). Either artificial cerebrospinal fluid (ACSF;n= 4) or Org 2766 (0.67 nmol kg−1every 4 h for 52 h;n= 4), was administered directly into the VNC via a stainless steel cannula connected to an osmotic minipump implanted s.c. Three symptoms of UL, spontaneous ocular nystagmus (SN), roll head tilt (RHT) and yaw head tilt (YHT), were measured at 10, 20, 25, 30, 40, 45 and 50 h post-UL. Org 2766 produced a significant decrease in the frequency of SN and accelerated its compensation. Org 2766 had no significant effect on either the compensation of RHT or YHT. This result suggests that vestibular compensation is enhanced by short ACTH fragments as a result of direct action on the ipsilateral VNC itself.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The termination pattern of the cervicothalamic tract (CTT), labelled with antcrogradely transported WGA- HRP, was compared with the immunolabelling pattern obtained with the monoclonal antibody Cat301 in adjacent sections through the ventral posterolateral nucleus (VPL). CTT terminations are located in peripheral parts of the medial and lateral parts of the VPL (VPLm and VPL1), being more extensive in the caudal than in the rostral parts of the subnuclei, and in the dorsal part of VPL1 and dorsolateral part of VPLm, regions that are all sparse in Cat301 immunoreactivity. Central regions of the VPI. with dense Cat301 immunolabelling contain only very sparse CTT termination. Thus, our findings show that the CTT innervates a compartment of the VPI. that is characterized by sparse Cat301 immunoreactivity.

ISSN:0959-4965    

出版商:OVID    

年代:1996

数据来源: OVID