摘要:

We propose that Alzheimer's disease is initiated by failure of axonal transport. After the neurodegeneration cascade is initiated, microglial and astroglial cells have major roles in directly and indirectly promoting self-sustaining neurodegeneration cycles. This hypothesis makes testable predictions and suggests logical therapies.

ISSN:0959-4965    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The mechanisms underlying the expression of long-term synaptic potentiation (LTP) in the lateral and medial perforant path inputs to the dentate gyrus were examined in pentobarbital anaesthetized rats. Lateral path LTP was accompanied by a robust, long-lasting reduction in lateral path paired-pulse facilitation (PPF). The reduction in PPF lasted for at least 1 h, and remained even after post-tetanic EPSP slopes were reduced to pre-tetanus levels. The induction of lateral path LTP and the corresponding reduction in PPF were blocked by the competitive NMDA receptor antagonist CPP. Medial path paired-pulse depression was not affected by medial path LTP. These data suggest that changes in transmitter release may contribute more to lateral path than to medial path LTP.

ISSN:0959-4965    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The effects of cyclothiazide, a drug that blocks AMPA receptor desensitization, on synaptic responses were studied in field CA1 of hippocampal slices from adult and neonatal rats. Cyclothiazide (100μM) reliably increased AMPA receptor-mediated field EPSP decay times in adult slices but only after prolonged (60–120 min) applications. In neonatal slices, 30 min applications of cyclothiazide were sufficient to produce large and long-lasting increases in response decay times. Since the effects of cyclothiazide on AMPA receptor binding properties were similar in adult and neonatal forebrain membranes, the data indicate that the slow action of the drug in adult slices is probably due to diffusion barriers. The prolongation of EPSP decay by cyclothiazide suggests that AMPA receptor-mediated synaptic responses in hippocampus are terminated by receptor desensitization.

ISSN:0959-4965    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Arachidonic acid has been proposed as a diffusible second messenger in the CNS with a pathophysiological role in epilepsy and stroke and a physiological role in long-term potentiation. These actions are possibly due to the ability of arachidonic acid to enhance extraneuronal glutamate concentration. In this present study we have investigated the effect of flurbiprofen, a cyclo-oxygenase inhibitor, on both potassium- and veratridine-stimulated release of glutamate from rat cerebellar slices. Flurbiprofen (100–500μM) had no effect on basal release but significantly increased stimulated release. The NMDA receptor antagonist CPP abolished the flurbiprofen-induced potentiation to both modes of stimulation, whilst the metabotropic glutamate receptor antagonist, L-AP3, blocked potassium-stimulated enhancement but had a variable effect on veratridine-stimulated release.

ISSN:0959-4965    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The effect of NGF on [Ca2+]iof mature regenerating oligodendroglial cells was investigated by measuring fluo-3 fluorescence. NGF caused transient increases in [Ca2+]i, which could be inhibited by anti-NGF antibody. The rise in [Ca2+]iwas in part due to influx of extracellular Ca2+since it was markedly attenuated in Ca2+-free solution. It also depended on release of Ca2+from intracellular stores as tested by prior depletion with cyclopiazonic acid. These results support a role for Ca2+in the effects of NGF on oligodendroglial cells.

ISSN:0959-4965    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

A study of the possible modulation by nitric oxide (NO) of endogenous dopamine (DA) release was performed in bovine retinain vitro. NO synthase activity was measured in retinal homogenates and totally blocked by L-nitroarginine methyl ester (L-NA). Intact retinas were also exposed to hydroxylamine, an NO-generator which significantly decreased both basal and potassium-induced liberation of DA. In contrast, dibutyryl cGMP was ineffective. Furthermore, L-NA was able to increase basal DA release, its effects being potentiated in calcium free medium. Taken together, these results suggest that endogenous NO regulates DA release via cGMP independent mechanisms.

ISSN:0959-4965    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The effects ofβ-amyloid protein 1–40 (βAP 1–40), substance P (SP), and the amidated and carboxylic acid C-terminated forms of the SP homologousβAP fragment 25–35 (βAP 25–35-NH2andβAP 25–35-COOH) were studied on [3H]MK-801 binding to the rat brain NMDA receptor cation channel. All peptides gave dose-dependent enhancements of [3H]MK-801 binding stimulated by low glycine.βAP 25–35-COOH, but notβAP 25–35-NH2produced an inhibition of [3H]MK-801 binding stimulated by high glycine in the presence of either low or high glutamate. Low glutamate-stimulated [3H]MK-801 binding was also inhibited by SP but not byβAP 1–40. It is concluded thatβAP related peptides exert differential effects on the NMDA receptor complex at the glycine and possibly also the glutamate recognition sites.

ISSN:0959-4965    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Facial nerve transection leads to functional and structural reactions in lesioned motor neurones and surrounding glial cells. Data from this study provide evidence that the most rapid reaction described so far consists of an increase in immunoreactivity of connexin-43 (cx-43), the predominant gap junction protein in astrocytes. The ipsilateral facial nucleus is selectively marked as early as 0.75 to 1.5 hours after axotomy, while the unlesioned side as well as the unoperated controls remain faintly stained. Thus, enhanced coupling capacity of astrocytes by gap junctions appears to be a sensitive indicator of modified neuronalglial interaction in the CNS.

ISSN:0959-4965    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Nerve growth factor (NGF) injected into the otherwise unlesioned adult rat septum induced sprouting of presumptive cholinergic fibres positive for p75NGFRand acetylcholinesterase (AChE). These fibres did not stain for tyrosine hydroxylase and therefore did not represent sympathetic ingrowth. Neurofilament staining on adjacent sections revealed fibres with similar morphology, suggesting new outgrowth in the form of sprouting rather than the upregulation of p75NGFRand AChE in pre-existing fibres. Simultaneous injections of subneurotoxic doses ofN-methyl-D-aspartate (NMDA) significantly potentiated the effect of NGF on cholinergic fibre sprouting and caused pronounced glial fibrillary acidic protein (GFAP)-positive astrocytosis. Application of NMDA alone did not elicit sprouting of this type. These findings indicate that NGF can induce the sprouting of uninjured adult rat septal cholinergic fibresin vivoand suggest that reactive astrocytes are not inhibitory to cholinergic axonal outgrowth, and might serve as a substrate for growing axons in the presence of NGF.

ISSN:0959-4965    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Cerebral vasodilatory responses are selectively impaired in chronically hyperglycemic, diabetic rats. In this study, we tested the hypothesis that chronic hyperglycemia-induced protein kinase C (PKC) activation can account for the suppression of 2 separate receptor-mediated vascular relaxation processes: (1) endothelium-derived nitric oxide (NO) release, and (2) NO-independentβ-adrenergic receptor (β-AR) activation. Thein vivoreactivity of pial arterioles was evaluated in anesthetized rats (streptozotocin-treated diabetics and controls) using a closed cranial window and intravital microscopy. Compared with controls, diabetic rats showed a substantial attenuation or loss of the arteriolar relaxation response accompanying suffusion of the receptor-linked, NO-dependent agonists, acetylcholine (Ach) and adenosine diphosphate (ADP), and theβ-AR-agonist, isoproterenol (ISO). The vasodilatation induced by the direct NO donor, sodium nitroprusside (SNP), was the same in both groups. In the presence of the PKC inhibitor, staurosporine (STAURO), the Ach, ADP, and ISO responses were, largely restored and the SNP response was unaffected. STAURO produced no changes in Ach, ADP, ISO, or SNP responses in non-diabetic rats. These results suggest that PKC activation in chronically hyperglycemic, diabetic rats suppresses receptor-dependent NO release and desensitizesβ-ARs.

ISSN:0959-4965    

出版商:OVID    

年代:1994

数据来源: OVID