Department of Pharmacy, The People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical Sciences, Nanning, P. R. China.
School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, P. R. China.
Ann Neurol. 2024 Sep;96(3):488-507. doi: 10.1002/ana.27001. Epub 2024 Jun 11.
The role of gamma-aminobutyric acid-ergic (GABAergic) neuron impairment in Alzheimer's disease (AD), and if and how transplantation of healthy GABAergic neurons can improve AD, remain unknown.
Human-derived medial ganglionic eminence progenitors (hiMGEs) differentiated from programmed induced neural precursor cells (hiNPCs) were injected into the dentate gyrus region of the hippocampus (HIP).
We showed that grafts migrate to the whole brain and form functional synaptic connections in amyloid precursor protein gene/ presenilin-1 (APP/PS1) chimeric mice. Following transplantation of hiMGEs, behavioral deficits and AD-related pathology were alleviated and defective neurons were repaired. Notably, exosomes secreted from hiMGEs, which are rich in anti-inflammatory miRNA, inhibited astrocyte activation invitro and in vivo, and the mechanism was related to regulation of CD4 Th1 cells mediated tumor necrosis factor (TNF) pathway.
Taken together, these findings support the hypothesis that hiMGEs transplantation is an alternative treatment for neuronal loss in AD and demonstrate that exosomes with anti-inflammatory activity derived from hiMGEs are important factors for graft survival. ANN NEUROL 2024;96:488-507.
γ-氨基丁酸能（GABAergic）神经元损伤在阿尔茨海默病（AD）中的作用，以及健康的 GABAergic 神经元移植是否可以改善 AD 以及如何改善 AD，目前尚不清楚。
将源自可编程诱导神经前体细胞（hiNPCs）的人源性内侧神经节隆起祖细胞（hiMGEs）注射到海马体（HIP）的齿状回区域。
我们表明，移植物迁移到整个大脑并在淀粉样前体蛋白基因/早老素-1（APP/PS1）嵌合小鼠中形成功能性突触连接。hiMGE 移植后，行为缺陷和 AD 相关病理得到缓解，受损神经元得到修复。值得注意的是，hiMGE 分泌的富含抗炎 miRNA 的外泌体在体外和体内抑制星形胶质细胞激活，其机制与调节 CD4 Th1 细胞介导的肿瘤坏死因子（TNF）途径有关。
综上所述，这些发现支持 hiMGE 移植是治疗 AD 神经元丢失的一种替代方法的假设，并表明源自 hiMGE 的具有抗炎活性的外泌体是移植物存活的重要因素。ANN NEUROL 2024；96:488-507。
