Strada O, Vyas S, Hirsch E C, Ruberg M, Brice A, Agid Y, Javoy-Agid F
Institut National de la Santé et de la Recherche Médicale U289, Hôpital de la Salpêtrière, Paris, France.
Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9549-53. doi: 10.1073/pnas.89.20.9549.
The subnormal choline acetyltransferase (ChoAcTase) activity in the cerebral cortex of patients with Alzheimer disease (AD) is thought to originate from the loss of cholinergic neurons in the nucleus basalis of Meynert (nbM). To examine possible changes in the functional activity of the remaining cholinergic neurons in the nbM of patients with AD, the level of expression of ChoAcTase mRNA was evaluated. A procedure for double-labeling cholinergic neurons to detect ChoAcTase mRNA and the corresponding protein in the same cell was developed, taking advantage of an anti-ChoAcTase antibody and the recently isolated cDNA complementary to a sequence of the human ChoAcTase mRNA. In the study of three controls and four patients with AD, the presence of both ChoAcTase mRNA and protein was observed in the same large neurons in both nbM and putamen. Specificity of in situ hybridization was further supported by the absence of neuronal staining with a sense probe. In AD patients a subnormal level of expression of ChoAcTase mRNA per cholinergic cell was detected in the nbM but not in the putamen. Our data support the hypothesis that expression of ChoAcTase mRNA might be down-regulated in the surviving cholinergic neurons in the nbM of patients with AD, raising the possibility of functional restoration by stimulating ChoAcTase synthesis.
阿尔茨海默病（AD）患者大脑皮质中胆碱乙酰转移酶（ChoAcTase）活性低于正常水平，被认为源于梅纳特基底核（nbM）中胆碱能神经元的丧失。为了检测AD患者nbM中剩余胆碱能神经元功能活性的可能变化，对ChoAcTase mRNA的表达水平进行了评估。利用抗ChoAcTase抗体和最近分离的与人类ChoAcTase mRNA序列互补的cDNA，开发了一种对胆碱能神经元进行双重标记的方法，以在同一细胞中检测ChoAcTase mRNA和相应的蛋白质。在对3名对照者和4名AD患者的研究中，在nbM和壳核的同一大神经元中均观察到了ChoAcTase mRNA和蛋白质的存在。正义探针未出现神经元染色，进一步支持了原位杂交的特异性。在AD患者中，nbM中每个胆碱能细胞的ChoAcTase mRNA表达水平低于正常，但壳核中未出现这种情况。我们的数据支持这样一种假说，即AD患者nbM中存活的胆碱能神经元中ChoAcTase mRNA的表达可能下调，这增加了通过刺激ChoAcTase合成实现功能恢复的可能性。
