Smith M L, Booze R M
Department of Pharmacology and Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington 40536-0084, USA.
Neuroscience. 1995 Aug;67(3):679-88. doi: 10.1016/0306-4522(95)00076-u.
Antibodies directed against choline acetyltransferase and glutamic acid decarboxylase were used in combination with recently developed stereological techniques to quantify changes in cholinergic, GABAergic, and total neuron number (Nissl-stain) within adjacent tissue sections through the horizontal limb/nucleus basalis in young (3 months, n = 6) and aged (27 months, n = 6) Fischer-344 male rats. Unbiased estimates of total neuron number within these regions were produced using a three-dimensional optical probe, the optical disector, in combination with a systematic random sampling scheme. Estimates of cell counts in immunostained tissue sections were conducted throughout the entire horizontal limb/nucleus basalis region. A significant 30% decrease in both cholinergic and total neuron number was detected in the aged animals; GABAergic neuron number remained unchanged. Total neuron number was significantly correlated with both cholinergic (r = 0.94) and glial cell number (r = 0.63), but not with GABAergic cell number. Based on neuron counts within an individual thick tissue section, the cholinergic neurons comprised only 11-15% of all neurons in the nucleus basalis of young and aged animals. Cholinergic neuron loss accounted for only 20% of the total age-related neuron loss within the horizontal limb/nucleus basalis in Fischer-344 male rats. These results indicate that age-related cholinergic neuron loss within the basal forebrain is reflected in reductions in total neuron number; however, GABAergic neurons, many of which project to the cortex, are unaffected by age. The magnitude of the age-related total neuron loss cannot be entirely accounted for by cholinergic cell loss. Therefore, an unidentified non-cholinergic, non-GABAergic component within the basal forebrain is also lost during aging and may contribute to the cognitive deficits previously ascribed to cholinergic dysfunction.
针对胆碱乙酰转移酶和谷氨酸脱羧酶的抗体与最近开发的体视学技术相结合，以量化年轻（3个月，n = 6）和老年（27个月，n = 6）的Fischer-344雄性大鼠水平支/基底核相邻组织切片中胆碱能、γ-氨基丁酸能和总神经元数量（尼氏染色）的变化。使用三维光学探针——光学分割器结合系统随机抽样方案，对这些区域内的总神经元数量进行无偏估计。在整个水平支/基底核区域对免疫染色组织切片中的细胞计数进行估计。在老年动物中，胆碱能和总神经元数量均显著减少30%；γ-氨基丁酸能神经元数量保持不变。总神经元数量与胆碱能神经元数量（r = 0.94）和神经胶质细胞数量（r = 0.63）均显著相关，但与γ-氨基丁酸能细胞数量无关。根据单个厚组织切片中的神经元计数，胆碱能神经元仅占年轻和老年动物基底核中所有神经元的11%-15%。在Fischer-344雄性大鼠的水平支/基底核内，胆碱能神经元的损失仅占与年龄相关的总神经元损失的20%。这些结果表明，基底前脑内与年龄相关的胆碱能神经元损失反映在总神经元数量的减少上；然而，许多投射到皮层的γ-氨基丁酸能神经元不受年龄影响。与年龄相关的总神经元损失的程度不能完全由胆碱能细胞损失来解释。因此，基底前脑内一种未明确的非胆碱能、非γ-氨基丁酸能成分在衰老过程中也会丢失，这可能导致先前归因于胆碱能功能障碍的认知缺陷。
