NEUROTRANSMITTER-RELATED ENZYMES AND INDEXES OF HYPOXIA IN SENILE DEMENTIA AND OTHER ABIOTROPHIES
NEUROTRANSMITTER-RELATED ENZYMES AND INDEXES OF HYPOXIA IN SENILE DEMENTIA AND OTHER ABIOTROPHIES
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DOI：
10.1093/brain/99.3.459
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发表时间：
1976-01-01
期刊：
影响因子：
14.5
通讯作者：
DAVISON, AN
中科院分区：
文献类型：
--
作者：
BOWEN, DM;SMITH, CB;DAVISON, AN
对五十六例正常中老年人和痴呆患者以及临床诊断为其他神经和精神疾病的患者的大脑进行组织学评估。在此基础上，将标本分为14个诊断组。对这些大脑进行了特定神经元的潜在指数调查，其中在多达20个大脑区域中确定了神经递质相关酶、γ-GTP（毛细血管的潜在指数）和特定蛋白质。此外，通过检查死后循环和呼吸系统的状态，对濒死状态进行了初步评估。CAT和γ-GTP活性和可溶性神经元型蛋白（神经元素S-5）的浓度被认为是相对不受濒死状态。当老年痴呆症病例与对照组（死亡原因相匹配）相比时，大脑皮层中CAT（胆碱能神经元的潜在指数）的活性似乎降低了。这是一个初步的发现，虽然CAT活性和“老年”形态学变化之间的相关性表明，活性显着降低，只有3个大脑。然而，尽管文献中存在不一致之处（Karczmar，1975），但至少有一项人体药理学研究似乎表明胆碱能系统可能与年龄相关的记忆退化有关（Drachman和Leavitt，1974）。胆碱能神经元在其他非营养性疾病（亨廷顿舞蹈病、运动神经元病和混合型血管性和老年性痴呆）中可能异常。γ-GTP和神经元蛋白S-5（在大多数方面与抗原α的可溶性酸性神经元蛋白14-3-2相同）在老年性痴呆中没有减少。脑脱羧酶（GAD和AAD）的活性和另一种可溶性酸性脑蛋白（神经元素S-6）的浓度似乎受到濒死状态的影响。这是值得注意的，因为GAD，特别是神经素S6，相对不受死后自溶的影响。根据调节大脑血液和氧气供应的神经系统的状态来判断，似乎是终末“大脑缺氧”导致了这些大脑成分的消耗。这种效应在深灰质中表现得尤为明显。在死于支气管肺炎的非痴呆患者中，皮质中神经元素S-6耗尽的区域与皮质对缺氧的“选择性脆弱性”模式一致，这表明终末状态也会影响新皮质。如果是这样的话，那么这与老年痴呆症的研究特别相关，因为在这些患者中经常发生的终末支气管肺炎（以及其他非生物营养不良的患者）的影响可能会因脑血流量的终末减少而加剧......
Fifty-six brains from middle-aged and elderly normal as well as demented subjects and patients with provisional clinical diagnosis of other neurological and psychiatric diseases were assessed histologically. On this basis the specimens were classified into 14 diagnostic groups. A survey of potential indices of specific neurons has been carried out on these brains in which neurotransmitter-related enzymes, gamma-GTP (a potential index of capillaries) and specific proteins have been determined in up to 20 brain regions. In addition, the agonal state has been tentatively assessed by examining the post-mortem states of the circulatory and respiratory systems. CAT and gamma-GTP activities and the concentration of a soluble neuronal-type protein (neuronin S-5) were found to be relatively unaffected by the agonal state. When cases of senile dementia were compared to controls (matched with respect to the cause of death) the activity of CAT (the potential index of cholinergic neurons) appears to be reduced in the cerebral cortex. This is a preliminary finding, although a correlation was indicated between CAT activity and'senile'morphological changes, the activity was markedly reduced in only 3 brains. However, despite inconsistencies in the literature (Karczmar, 1975) at least one pharmacological study on humans appears to show that the cholinergic system may be involved in age-related memory degeneration (Drachman and Leavitt, 1974). Cholinergic neurons may be abnormal in the other abiotrophies examined (Huntington's chorea, motor neuron disease and mixed vascular and senile dementia). gamma-GTP and neuronin S-5 (identical in most respects to the soluble acidic neuronal protein 14-3-2 of antigen alpha) were not reduced in senile dementia. The activities of brain decarboxylase (GAD and AAD) and the concentration of another soluble acidic brain protein (neuronin S-6) appear to be affected by the agonal state. This is remarkable because GAD and, in particular, neuronin S6, are relatively unaffected by post-mortem autolysis. As judged by the state of the extraneural systems which regulated the blood and oxygen supply to the brain it appears that terminal'cerebral hypoxia'is responsible for the depletion of these brain constituents. This effect appears to be particularly marked in deep grey matter. In non-demented patients that die of bronchopneumonia, the areas of the cortex which are depleted in neuronin S-6 are consistent with the pattern of the'selective vulnerability'of the cortex to hypoxia, suggesting that the terminal state can also affect the neocortex. If so, then this is particularly relevant to studies on senile dementia, for the effect of the terminal bronchopneumonia that so often occurs in these patients (and in patients with other abiotrophies) may be exacerbated by a terminal reduction in cerebral blood flow...