Johnston M V, Hohmann C, Blue M E
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Neuropediatrics. 1995 Apr;26(2):119-22. doi: 10.1055/s-2007-979740.
From a neurobiologic perspective, Rett syndrome appears to disrupt the growth of axonodendritic connections among neurons. The cell packing density within the grey matter is increased but the total number of neurons is relatively normal, except for selected neuronal populations such as the nucleus basalis of Meynert (NBM) and the substantia nigra. Neurochemical assays of postmortem brain from patients with Rett syndrome patients demonstrate reductions in choline acetyltransferase (ChAT), the acetylcholine synthetic enzyme localized in NBM nerve terminals. In an animal model, early postnatal injury to the cholinergic pathways projected from the NBM causes permanent disruption of developing cholinergic neurons and a behavioral disorder on maze testing. The results suggest a mechanism by which early deficits in cholinergic and dopamine neurons projecting to the cerebral cortex from the brainstem and basal forebrain could disrupt axonodendritic development in the cerebral cortex. Studies in our laboratory are examining the mechanisms for these effects as well as the distribution and densities of neurotransmitter receptors in postmortem brains from Rett patients.
从神经生物学角度来看，雷特综合征似乎会扰乱神经元之间轴突树突连接的生长。灰质内的细胞堆积密度增加，但神经元总数相对正常，除了某些特定的神经元群体，如梅纳特基底核（NBM）和黑质。对雷特综合征患者死后大脑进行的神经化学分析表明，胆碱乙酰转移酶（ChAT）减少，该酶是位于NBM神经末梢的乙酰胆碱合成酶。在一个动物模型中，出生后早期对从NBM投射出的胆碱能通路造成损伤，会导致发育中的胆碱能神经元永久性破坏，并在迷宫测试中出现行为障碍。这些结果提示了一种机制，即从脑干和基底前脑投射到大脑皮层的胆碱能和多巴胺能神经元的早期缺陷可能会扰乱大脑皮层的轴突树突发育。我们实验室的研究正在探究这些效应的机制，以及雷特患者死后大脑中神经递质受体的分布和密度。
