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[记忆机制的老化]

[Aging of memory mechanisms].

作者信息

Lamour Y, Bassant M H, Potier B, Billard J M, Dutar P

机构信息

INSERM, Unité de Recherche de Physiopharmacologie du Système Nerveux, Paris.

出版信息

C R Seances Soc Biol Fil. 1994;188(5-6):469-86.

PMID:7780790
Abstract

Human amnesia cases (after surgical removal of the hippocampi or brain anoxia) have clearly established the critical role of the hippocampal formation in anterograde amnesia. Other parts of the brain may also contribute to anterograde amnesia (mammillary bodies, medial thalamus). In neurodegenerative diseases (and specially in Alzheimer's disease) amnesia is often the prominent symptom, but the brain lesions are not restricted to the hippocampal formation. In Alzheimer's disease they involve also the cerebral cortex and several subcortical nuclei. Physiological brain aging is also associated with some degree of memory impairment, but much less severe than in Alzheimer's disease. The issue of the nature and the mechanisms of the memory impairment associated with age and with Alzheimer's disease is very important, because the frequency of these problems increases dramatically as the populations of the world is growing older. There is some evidence that neuronal loss and alterations in neurotransmitter systems occur in the aged subject, but the relationship between such changes and the age-related memory deficit is far from being clear. In Alzheimer's disease, the loss of memory is likely to be due to neuronal loss in cerebral cortex and hippocampal formation, along with alterations in neurotransmitter systems (specially cholinergic, monoaminergic and aminoacidergic systems). The work in experimental animals has largely confirmed the critical role of the hippocampal formation, as well as identified other critical structures. The mechanisms of the age-related memory impairment can be to some extent investigated in aged animals. In the aged rat there is evidence that several neurotransmitter networks are altered. Alteration in the dopaminergic and cholinergic systems have been extensively studied, but the involvement of other systems is likely. Learning and memory deficits are consistently observed in a sub-population of aged rodents (as well as in other species including non-human primates). For instance some aged rats do have a deficit in the performance of a spatial learning task such as the "water maze". There is some evidence that this deficit is due, at least in part, to alterations in the functions of the hippocampal formation. In other words, if aged rats have a spatial memory deficit, it might be due to changes in hippocampal neuronal circuitry. The study of age-related alterations in hippocampal neuronal networks, using electrophysiological techniques have shown that several neuronal properties such as resting membrane potential, membrane resistance or sodium spike amplitude are not altered in the aged rat hippocampus.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

人类失忆病例(在手术切除海马体或脑部缺氧后)已明确证实海马结构在顺行性失忆中起关键作用。大脑的其他部分也可能导致顺行性失忆(乳头体、内侧丘脑)。在神经退行性疾病(特别是阿尔茨海默病)中,失忆往往是突出症状,但脑部病变并不局限于海马结构。在阿尔茨海默病中,病变还累及大脑皮层和几个皮层下核团。生理性脑老化也与一定程度的记忆障碍有关,但比阿尔茨海默病轻得多。与年龄和阿尔茨海默病相关的记忆障碍的本质和机制问题非常重要,因为随着世界人口老龄化,这些问题的发生率急剧上升。有证据表明,老年受试者会出现神经元丢失和神经递质系统改变,但这种变化与年龄相关的记忆缺陷之间的关系尚不清楚。在阿尔茨海默病中,记忆丧失可能是由于大脑皮层和海马结构中的神经元丢失,以及神经递质系统(特别是胆碱能、单胺能和氨基酸能系统)的改变。对实验动物的研究在很大程度上证实了海马结构的关键作用,并确定了其他关键结构。与年龄相关的记忆障碍机制在一定程度上可以在老年动物中进行研究。在老年大鼠中,有证据表明几个神经递质网络发生了改变。多巴胺能和胆碱能系统的改变已得到广泛研究,但其他系统也可能参与其中。在老年啮齿动物(以及包括非人类灵长类动物在内的其他物种)的一个亚群中持续观察到学习和记忆缺陷。例如,一些老年大鼠在空间学习任务(如“水迷宫”)的表现上存在缺陷。有证据表明,这种缺陷至少部分是由于海马结构功能的改变。换句话说,如果老年大鼠存在空间记忆缺陷,可能是由于海马神经元回路的变化。使用电生理技术对海马神经元网络中与年龄相关的变化进行的研究表明,老年大鼠海马中的一些神经元特性,如静息膜电位、膜电阻或钠峰电位幅度并未改变。(摘要截选至400字)

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