De Bartolo Paola, Gelfo Francesca, Mandolesi Laura, Foti Francesca, Cutuli Debora, Petrosini Laura
IRCCS Santa Lucia Foundation, Rome, Italy.
J Alzheimers Dis. 2009;17(1):177-91. doi: 10.3233/JAD-2009-1035.
Although clinical and experimental research has demonstrated that acetylcholinesterase inhibitors, such as donepezil, are able to enhance cognitive functioning in intact subjects as well as in patients affected by different degrees of dementia, no morphological study has ever analyzed whether donepezil treatment is able to modify neocortical neuronal morphology in the intact brain and in response to cholinergic depletion. Spines (number, density, distribution) and branching (length, intersections, nodes) of apical and basal dendrites of III-layer parietal pyramidal neurons were evaluated following chronic donepezil treatment in intact animals and in animals in which the cholinergic lesion was produced by intracerebroventricular injections of immunotoxin 192 IgG-saporin. In intact animals, the drug treatment provoked a proximal shift of spines towards the cell soma in basal dendrites. In lesioned animals, donepezil treatment reduced the upregulation of the spines induced by the cholinergic lesion in both apical and basal dendrites. Thus, while in the intact brain chronic donepezil treatment induced plastic changes in the dendritic morphology of pyramidal neurons of parietal cortex, in the presence of cholinergic depletion, it prevented the compensatory response of parietal pyramidal neurons to the loss of cholinergic inputs from basal forebrain.
尽管临床和实验研究表明，多奈哌齐等乙酰胆碱酯酶抑制剂能够增强正常受试者以及不同程度痴呆患者的认知功能，但尚无形态学研究分析多奈哌齐治疗是否能够改变正常大脑中以及对胆碱能耗竭做出反应时新皮质神经元的形态。在正常动物以及通过脑室内注射免疫毒素192 IgG-皂草素产生胆碱能损伤的动物中，对慢性多奈哌齐治疗后第III层顶叶锥体神经元的顶树突和基底树突的棘（数量、密度、分布）和分支（长度、交叉点、节点）进行了评估。在正常动物中，药物治疗导致基底树突中的棘向细胞体近端移位。在损伤动物中，多奈哌齐治疗减少了顶树突和基底树突中由胆碱能损伤诱导的棘上调。因此，在正常大脑中，慢性多奈哌齐治疗可诱导顶叶皮质锥体神经元树突形态发生可塑性变化，而在存在胆碱能耗竭的情况下，它可阻止顶叶锥体神经元对来自基底前脑的胆碱能输入丧失的代偿反应。
