在阿尔茨海默病患者的快速尸检材料中评估的突触前胆碱能功能的调节变化：对病因学和治疗的影响。
Regulatory changes in presynaptic cholinergic function assessed in rapid autopsy material from patients with Alzheimer disease: implications for etiology and therapy.
作者信息
Slotkin T A, Seidler F J, Crain B J, Bell J M, Bissette G, Nemeroff C B
机构信息
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
出版信息
Proc Natl Acad Sci U S A. 1990 Apr;87(7):2452-5. doi: 10.1073/pnas.87.7.2452.
Abstract
Brain regions from patients with or without Alzheimer disease (AD) were obtained within 2 hr of death and examined for indices of presynaptic cholinergic function. Consistent with loss of cholinergic projections, cerebral cortical areas involved in AD exhibited decreased choline acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6) activity. However, remaining nerve terminals in these regions displayed marked up-regulation of synaptosomal high affinity [3H]choline uptake, a result indicative of relative cholinergic hyperactivity. As choline uptake is also rate-limiting in acetylcholine biosynthesis, these findings have implications for both therapy and identification of causes contributing to neuronal death in AD.
摘要
在患者死亡后2小时内获取患有或未患有阿尔茨海默病（AD）患者的脑区，并检查其突触前胆碱能功能指标。与胆碱能投射丧失一致，AD所涉及的大脑皮质区域显示胆碱乙酰转移酶（乙酰辅酶A：胆碱O-乙酰转移酶，EC 2.3.1.6）活性降低。然而，这些区域中剩余的神经末梢显示突触体高亲和力[3H]胆碱摄取显著上调，这一结果表明胆碱能相对亢进。由于胆碱摄取在乙酰胆碱生物合成中也是限速步骤，这些发现对AD中神经元死亡的治疗和病因识别均有启示意义。
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本文引用的文献
1
A post-mortem study of the cholinergic and GABA systems in senile dementia.老年痴呆症中胆碱能和γ-氨基丁酸系统的尸检研究。
Brain. 1982 Jun;105(Pt 2):313-30. doi: 10.1093/brain/105.2.313.
2
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J Neurochem. 1983 Feb;40(2):503-9. doi: 10.1111/j.1471-4159.1983.tb11311.x.
3
Evidence for high affinity choline transport in synaptosomes prepared from hippocampus and neocortex of patients with Alzheimer's disease.阿尔茨海默病患者海马体和新皮质制备的突触体中高亲和力胆碱转运的证据。
Brain Res. 1983 Dec 19;289(1-2):169-75. doi: 10.1016/0006-8993(83)90017-3.
4
Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer's disease.阿尔茨海默病中血清素能和胆碱能功能障碍及脑萎缩的生化评估
J Neurochem. 1983 Jul;41(1):266-72. doi: 10.1111/j.1471-4159.1983.tb11838.x.
5
6
Muscarinic receptor subtypes in hippocampus in Alzheimer's disease and mixed dementia type.阿尔茨海默病和混合型痴呆中海马体的毒蕈碱受体亚型
Neurosci Lett. 1986 Sep 25;70(1):160-4. doi: 10.1016/0304-3940(86)90456-8.
7
Nicotinic acetylcholine binding sites in Alzheimer's disease.阿尔茨海默病中的烟碱型乙酰胆碱结合位点
Brain Res. 1986 Apr 16;371(1):146-51. doi: 10.1016/0006-8993(86)90819-x.
8
Regulation of adrenal chromaffin cell development by the central monoaminergic system: differential control of norepinephrine and epinephrine levels and secretory responses.中枢单胺能系统对肾上腺嗜铬细胞发育的调节：去甲肾上腺素和肾上腺素水平及分泌反应的差异控制。
Neuroscience. 1987 Sep;22(3):1067-75. doi: 10.1016/0306-4522(87)92981-2.
9
Cellular localization of messenger RNA encoding amyloid-beta-protein in normal tissue and in Alzheimer disease.编码β-淀粉样蛋白的信使核糖核酸在正常组织和阿尔茨海默病中的细胞定位。
Alzheimer Dis Assoc Disord. 1988;2(2):96-111. doi: 10.1097/00002093-198802020-00002.
10
Diagnosis of Alzheimer's disease.阿尔茨海默病的诊断
Arch Neurol. 1985 Nov;42(11):1097-105. doi: 10.1001/archneur.1985.04060100083029.
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