Department of Neurology, Lanzhou University Second Hospital, Cuiyingmen 82, Chengguan District, Lanzhou, 730030, Gansu, China.
Brain Research Center and State Key Laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University, Chongqing, 400038, China.
Stem Cell Res Ther. 2022 Jun 28;13(1):285. doi: 10.1186/s13287-022-02959-0.
Aging causes astrocyte morphological degeneration and functional deficiency, which impairs neuronal functions. Until now, whether age-induced neuronal deficiency could be alleviated by engraftment of glial progenitor cell (GPC) derived astrocytes remained unknown. In the current study, GPCs were generated from embryonic cortical neural stem cells in vitro and transplanted into the brains of aged mice. Their integration and intervention effects in the aged brain were examined 12 months after transplantation. Results indicated that these in-vitro-generated GPC-derived astrocytes possessed normal functional properties. After transplantation they could migrate, differentiate, achieve long-term integration, and maintain much younger morphology in the aged brain. Additionally, these GPC-derived astrocytes established endfeet expressing aquaporin-4 (AQP4) and ameliorate AQP4 polarization in the aged neocortex. More importantly, age-dependent sensory response degeneration was reversed by GPC transplantation. This work demonstrates that rejuvenation of the astrocyte niche is a promising treatment to prevent age-induced degradation of neuronal and behavioral functions.
衰老导致星形胶质细胞形态退化和功能缺陷，从而损害神经元功能。到目前为止，胶质前体细胞（GPC）衍生的星形胶质细胞移植是否可以减轻年龄引起的神经元缺乏仍不清楚。在本研究中，从胚胎皮质神经干细胞体外生成 GPC 并移植到老年小鼠的大脑中。在移植后 12 个月检查它们在老年大脑中的整合和干预效果。结果表明，这些体外生成的 GPC 衍生的星形胶质细胞具有正常的功能特性。移植后，它们可以迁移、分化、长期整合，并在老年大脑中保持更年轻的形态。此外，这些 GPC 衍生的星形胶质细胞建立了表达水通道蛋白-4（AQP4）的足突，并改善了老年新皮质中的 AQP4 极化。更重要的是，GPC 移植逆转了与年龄相关的感觉反应退化。这项工作表明，星形胶质细胞生态位的年轻化是预防年龄引起的神经元和行为功能退化的一种有前途的治疗方法。
