Selden N, Geula C, Hersh L, Mesulam M M
Bullard and Denny-Brown Laboratories, Department of Neurology, Harvard Medical School, Boston, Massachusetts.
Neuroscience. 1994 Jun;60(3):621-36. doi: 10.1016/0306-4522(94)90491-x.
The morphology and distribution of perikarya positive for choline acetyltransferase, somatostatin, calcium binding protein (calbindin D28K) and nicotinamide adenine dinucleotide phosphate diaphorase were surveyed in the human striatum. Choline acetyltransferase and somatostatin antibodies labeled separate populations of large striatal interneurons. Somatostatin immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (nitric oxide synthase) activity were completely co-localized. Calbindin antibody identified two distinct groups of striatal neurons: (1) numerous medium-sized, lightly stained neurons, probably analogous to striatopallidal projection neurons in the rat, and (2) much less numerous, large, darkly stained neurons. Half of the latter group, but none of the former, were also nicotinamide adenine dinucleotide phosphate diaphorase-positive. Somatostatin-positive and medium-sized, calbindin-positive neurons were more numerous in the caudate nucleus than in the putamen or ventral striatum. By contrast, large calbindin-immunoreactive neurons were more frequently encountered in the putamen. Choline acetyltransferase-positive neurons were evenly distributed across striatal components. In aged control subjects, the size of large, darkly stained calbindin-positive neurons was reduced relative to young subjects. Aging had no effect on somatostatin-, medium-sized calbindin-, or choline acetyltransferase-positive neurons. However, in histologically confirmed cases of Alzheimer's disease, there was a selective, 75% loss of choline acetyltransferase-immunoreactive perikarya from the ventral striatum, but not from the dorsal striatum, compared to aged controls. Furthermore, the remaining cholinergic neurons in the ventral striatum of Alzheimer's disease cases were significantly smaller than similar neurons in controls. These results indicate that various striatal components which have been shown to differ in their anatomical connectivity and functional specialization, also differ in their neurochemical signatures. The specific and marked loss of choline acetyltransferase-positive neurons from the ventral striatum in Alzheimer's disease is consistent with the characteristic cholinergic and 'limbic' pathology in this disease.
我们对人纹状体中胆碱乙酰转移酶、生长抑素、钙结合蛋白（钙结合蛋白D28K）和烟酰胺腺嘌呤二核苷酸磷酸黄递酶呈阳性的神经元胞体的形态和分布进行了研究。胆碱乙酰转移酶和生长抑素抗体标记了纹状体中不同的大中间神经元群体。生长抑素免疫反应性和烟酰胺腺嘌呤二核苷酸磷酸黄递酶（一氧化氮合酶）活性完全共定位。钙结合蛋白抗体识别出两组不同的纹状体神经元：（1）大量中等大小、染色浅的神经元，可能类似于大鼠中的纹状体苍白球投射神经元，以及（2）数量少得多、大、染色深的神经元。后一组中有一半是烟酰胺腺嘌呤二核苷酸磷酸黄递酶阳性，而前一组中没有。生长抑素阳性和中等大小、钙结合蛋白阳性的神经元在尾状核中比在壳核或腹侧纹状体中更多。相比之下，大的钙结合蛋白免疫反应性神经元在壳核中更常见。胆碱乙酰转移酶阳性神经元均匀分布于纹状体各部分。在老年对照受试者中，与年轻受试者相比，大的、染色深的钙结合蛋白阳性神经元的大小减小。衰老对生长抑素、中等大小的钙结合蛋白或胆碱乙酰转移酶阳性神经元没有影响。然而，在组织学确诊的阿尔茨海默病病例中，与老年对照相比，腹侧纹状体中胆碱乙酰转移酶免疫反应性胞体有选择性地减少了75%，而背侧纹状体中没有。此外，阿尔茨海默病病例腹侧纹状体中剩余的胆碱能神经元明显小于对照组中的类似神经元。这些结果表明，已显示在解剖学连接和功能特化方面存在差异的各种纹状体成分，在神经化学特征上也存在差异。阿尔茨海默病中腹侧纹状体胆碱乙酰转移酶阳性神经元的特异性和明显丧失与该疾病的特征性胆碱能和“边缘系统”病理学一致。
