Strong R, Huang J S, Huang S S, Chung H D, Hale C, Burke W J
Geriatric Research, Education and Clinical Center, St. Louis Veterans Administration Medical Center, MO 63125.
Brain Res. 1991 Feb 22;542(1):23-8. doi: 10.1016/0006-8993(91)90992-5.
Choline acetyltransferase (Acetyl-CoA: choline O-acetyltransferase: EC 2.3.1.6) (ChAT) enzyme activity and neuron density were measured in the locus ceruleus (LC) of autopsied brains of neurologically normal individuals and patients who had Alzheimer's disease. Neuron density in the LC of individuals with Alzheimer's was significantly reduced to approximately 50% of normal values. ChAT activity was also reduced by about 50%. Furthermore, the number of pigmented neurons in the LC was highly correlated with presynaptic ChAT activity. These findings were specific for the LC, since deficits in ChAT and neuron density were not found in two adrenergic brainstem nuclei (C1 and C2). We measured mitogen activity in LC extracts in order to determine whether loss of cholinergic afferents to the LC, as evidenced by loss of ChAT, was related to putative trophic factors. Mitogen activity was significantly reduced (50%) in the Alzheimer's group as compared to normals. Mitogen activity was significantly correlated with ChAT activity and the density of neurons in the LC. The loss of cholinergic nerve terminals in the LC in Alzheimer's disease may be functionally significant, since acetylcholine has important effects on LC physiology. The highly significant relationships between ChAT, neuron density and mitogen activity has important implications for our understanding of mechanisms of neurodegeneration in Alzheimer's disease.
在神经功能正常个体以及患有阿尔茨海默病患者的尸检大脑蓝斑（LC）中，测定了胆碱乙酰转移酶（乙酰辅酶A：胆碱O - 乙酰转移酶：EC 2.3.1.6）（ChAT）的酶活性和神经元密度。阿尔茨海默病患者蓝斑中的神经元密度显著降低至正常值的约50%。ChAT活性也降低了约50%。此外，蓝斑中色素沉着神经元的数量与突触前ChAT活性高度相关。这些发现是蓝斑特有的，因为在两个肾上腺素能脑干核（C1和C2）中未发现ChAT和神经元密度的缺陷。我们测定了蓝斑提取物中的有丝分裂原活性，以确定如ChAT缺失所证明的，向蓝斑的胆碱能传入神经的丧失是否与假定的营养因子有关。与正常组相比，阿尔茨海默病组的有丝分裂原活性显著降低（50%）。有丝分裂原活性与ChAT活性以及蓝斑中的神经元密度显著相关。阿尔茨海默病中蓝斑胆碱能神经末梢的丧失可能具有功能意义，因为乙酰胆碱对蓝斑生理学有重要影响。ChAT、神经元密度和有丝分裂原活性之间的高度显著关系对我们理解阿尔茨海默病神经退行性变机制具有重要意义。
