Slotkin T A, Seidler F J, Crain B J, Bell J M, Bissette G, Nemeroff C B
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Proc Natl Acad Sci U S A. 1990 Apr;87(7):2452-5. doi: 10.1073/pnas.87.7.2452.
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.
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。