Pediatric Center, Zhujiang Hospital of the Southern Medical University, A- 3103, Building 39, No. 253 Gong-ye Road, Haizhu District, Guangzhou, 510280, Guangdong, China.
Department of Ear, Nose and Throat, Zhujiang Hospital of the Southern Medical University, Guangzhou, 510282, Guangdong, China.
Mol Neurobiol. 2019 Oct;56(10):7222-7233. doi: 10.1007/s12035-019-1588-0. Epub 2019 Apr 18.
The cholinergic neurons in the nucleus basalis of Meynert (NBM) are among the first group of neurons known to become degenerated in Alzheimer's disease, and thus the NBM is proposed to be involved in learning and memory. The marginal division (MrD) of the striatum is a newly discovered subdivision at the ventromedial border of the mammalian striatum and is considered to be one part of the ventral striatum involved in learning and memory. The present study provided evidence to support the hypothesis that the MrD and the NBM were structurally connected at cellular and subcellular levels with functional implications in learning and memory. First, when wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was stereotaxically injected into the NBM, fusiform neurons in the MrD were retrogradely labeled with WGA-HRP gray-blue particles and some of them were double stained in brown color by AchE staining method. Thus, cholinergic neurons of the MrD were shown to project to the neurons in the NBM. Second, in anterograde tract-tracing experiments where WGA-HRP was injected to the MrD, the labeled WGA-HRP was found to be anterogradely transported in axons from the MrD to the synaptic terminals with dendrites, axons, and perikaryons of the cholinergic neurons in the NBM when observed under an electronic microscope, indicating reciprocal structural connections between the MrD and the NBM. Third, when bilateral lesions of the MrD were injured with kainic acid in rats, degenerative terminals were observed in synapses of the NBM by an electronic microscope and severe learning and memory deficiency was found in these rats by the Y-maze behavioral test. Our results suggest reciprocal cholinergic connections between the MrD of the ventral striatum and the NBM, and implicate a role of the MrD-NBM pathway in learning and memory. The efferent fibers of cholinergic neurons in the NBM mainly project to the cortex, and severe reduction of the cholinergic innervation in the cortex is the common feature of Alzheimer's patients. The newly discovered cholinergic neural pathway between the MrD of the ventral striatum and the NBM is supposed involved in the memory circuitries of the brain and probably might play a role in the pathogenesis of the Alzheimer's disease.
基底前脑复合体（Meynert）的胆碱能神经元是已知在阿尔茨海默病中最早退化的神经元之一，因此基底前脑复合体被认为参与学习和记忆。纹状体的边缘区（MrD）是在哺乳动物纹状体腹侧边界新发现的一个细分区域，被认为是参与学习和记忆的腹侧纹状体的一部分。本研究提供了证据支持这样一种假设，即 MrD 和 NBM 在细胞和亚细胞水平上具有结构连接，并在学习和记忆方面具有功能意义。首先，当将辣根过氧化物酶（HRP）结合的麦胚凝集素（WGA-HRP）立体定向注射到 NBM 时，MrD 中的梭形神经元被 WGA-HRP 灰蓝色颗粒逆行标记，其中一些神经元被 AchE 染色法染成棕色。因此，显示 MrD 的胆碱能神经元投射到 NBM 的神经元。其次，在顺行示踪实验中，将 WGA-HRP 注射到 MrD 中，当在电子显微镜下观察时，发现标记的 WGA-HRP 沿 MrD 的轴突向前运输到突触末端，突触末端有 NBM 中胆碱能神经元的树突、轴突和胞体，表明 MrD 和 NBM 之间存在相互的结构连接。第三，当用红藻氨酸损伤大鼠双侧 MrD 时，电子显微镜观察到 NBM 中的突触出现退行性终末，这些大鼠在 Y 迷宫行为测试中表现出严重的学习和记忆缺陷。我们的结果表明，腹侧纹状体的 MrD 和 NBM 之间存在相互的胆碱能连接，并暗示 MrD-NBM 通路在学习和记忆中的作用。NBM 中的胆碱能神经元的传出纤维主要投射到皮层，而皮层中的胆碱能支配严重减少是阿尔茨海默病患者的共同特征。腹侧纹状体的 MrD 和 NBM 之间新发现的胆碱能神经通路被认为参与了大脑的记忆回路，并可能在阿尔茨海默病的发病机制中发挥作用。
Zotero 插件
