Neurotransmitter systems in aging and senile dementia

Edith G. McGeer
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引用次数: 61

Abstract

  • 1.

    1. Reported changes in neurotransmitter systems with aging in human and animal brain are briefly reviewed. The effects of age appear to vary from region to region in brain, as well as from system to system. Considerable evidence is available that dopaminergic activity decreases with age, particularly in the striatum and nucleus accumbens; this loss may be important to age-related losses in agility and increases in the incidence and severity of tardive dyskinesia. Lesser, but still convincing, evidence indicates decreases with age in noradrenergic, GABAergic and cholinergic systems, with the most marked effects being found, respectively, in the hypothalamus, thalamus and cortex-hippocampus. The cortical and hippocampal losses in cholinergic activity are markedly accentuated in senile dementia of the Alzheimer type and are probably related to memory defects in aging and dementia.

  • 2.

    2. Serotonin and met-enkephalin systems in the hypothalamus are probably relatively unchanged by age and little or no information is available on numerous other putative transmitters.

  • 3.

    3. Brief consideration is also given to age-related changes in the density of specific binding sites, possible reasons for lack of therapeutic effect of choline analogs in senile dementia, and the question of whether cell death, loss of nerve endings and/or decreased neuronal vitality underlie the deficits found.

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衰老和老年性痴呆的神经递质系统
1.1. 本文简要回顾了人类和动物大脑中神经递质系统随着衰老而发生的变化。年龄的影响似乎在大脑的不同区域和系统之间有所不同。大量证据表明,多巴胺能活性随着年龄的增长而下降,尤其是纹状体和伏隔核;这种损失可能对与年龄相关的敏捷性损失和迟发性运动障碍的发生率和严重程度的增加很重要。较少但仍然令人信服的证据表明,去甲肾上腺素能、gaba能和胆碱能系统随着年龄的增长而下降,其中最显著的影响分别出现在下丘脑、丘脑和皮质-海马中。皮层和海马胆碱能活性的丧失在阿尔茨海默型老年痴呆中明显加重,这可能与衰老和痴呆中的记忆缺陷有关。下丘脑中的5 -羟色胺和脑啡肽系统可能随着年龄的增长而相对不变,而且关于许多其他假定的递质的信息很少或没有。简要考虑了特定结合位点密度的年龄相关变化,胆碱类似物对老年性痴呆缺乏治疗效果的可能原因,以及细胞死亡、神经末梢丧失和/或神经元活力下降是否导致所发现的缺陷的问题。
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