Carlsson A
Department of Pharmacology, University of Gothenburg, Sweden.
Gerontology. 1987;33(3-4):159-67. doi: 10.1159/000212870.
Reductions of the levels of transmitter substances and of the activities of enzymes involved in their synthesis have been demonstrated in the aging brain. The sensitivity to the aging process varies for different transmitters and brain regions. Dopamine neurons are more age-sensitive than most other neurons investigated. The metabolism of monoaminergic neurotransmitters is enhanced in the aging brain, as evidenced by increased metabolite/neurotransmitter ratios, perhaps to compensate for the loss of transmitter. In various types of dementia, including Alzheimer's disease (AD) and senile dementia of Alzheimer type (SDAT), several neurotransmitter indices are reduced, as compared to age-matched controls. Moreover, a decrease in neurotransmitter metabolites suggests that compensatory mechanisms are insufficient. No correlation could be found between the neurotransmitter changes and the histological changes characteristic of AD (senile plaques and neurofibrillary tangles). Neither could any relationship between multiple infarctions and neurotransmitter indices be detected. Recently observed changes in the lipid composition of the white matter, indicating demyelinization, in the brains of patients with AD/SDAT, emphasize the multifactorial aspects of dementia. Taken together, the data underline the difficulties in drawing clear demarcation lines between normal and pathological aging and between different subgroups of dementia. Despite the obvious difficulties, future therapeutic efforts should aim at substitution for the neurotransmitter deficiencies. Preventive measures have to await the clarification of the mechanisms underlying neural degeneration. Studies of the toxicity of oxygen and of autoxidation products are among the areas of research that may help to shed light on this problem.
在衰老的大脑中，已证实神经递质物质水平及其合成过程中相关酶的活性有所降低。不同神经递质和脑区对衰老过程的敏感性各不相同。多巴胺神经元比大多数其他被研究的神经元对年龄更敏感。单胺能神经递质的代谢在衰老大脑中增强，代谢物/神经递质比值增加就证明了这一点，这可能是为了补偿神经递质的损失。在包括阿尔茨海默病（AD）和阿尔茨海默型老年痴呆（SDAT）在内的各种类型痴呆中，与年龄匹配的对照组相比，几种神经递质指标降低。此外，神经递质代谢物的减少表明补偿机制不足。在神经递质变化与AD的组织学特征（老年斑和神经原纤维缠结）之间未发现相关性。也未检测到多发性梗死与神经递质指标之间的任何关系。最近在AD/SDAT患者大脑中观察到的白质脂质组成变化，表明存在脱髓鞘现象，这突出了痴呆的多因素特点。综上所述，这些数据凸显了在正常衰老与病理性衰老以及不同痴呆亚组之间划定明确界限的困难。尽管存在明显困难，但未来的治疗努力应旨在替代神经递质缺乏。预防措施必须等待神经退行性变潜在机制的阐明。对氧毒性和自氧化产物的研究是可能有助于阐明这一问题的研究领域之一。
