Department of Neurology, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China.
BenQ Neurological Institute of Nanjing Medical University, Nanjing, China.
Neuropathology. 2020 Jun;40(3):224-231. doi: 10.1111/neup.12633. Epub 2020 Feb 9.
Neural stem cell (NSC) transplantation has emerged as a promising approach for the treatment of neurological disorders such as cerebral ischemia. As the majority of newly generated cells from exogenous NSCs fail to integrate into the ischemic brain and establish functional synaptic networks, NSC transplantation for ischemic stroke experiences limited neurological function recovery. Augment of endogenous neurite growth in the process of NSC differentiation is an avenue to promote synaptic networks. Phosphatase and tensin homolog (PTEN), a tumor suppressor, has been established to regulate axon growth in the adult central nervous system. The aim of this study was to explore the role of PTEN on neurite growth during NSC differentiation. Our results revealed that the protein expression of PTEN was significantly increased during NSC differentiation, whereas the expression of phosphorylated S6 ribosomal (p-S6R) was markedly decreased. Small interfering RNA knockdown of PTEN in NSCs can accelerate neurite outgrowth during NSC differentiation. These results indicated a remarkable effect of PTEN inhibition on neuronal process after NSC differentiation, and identified a novel route to promote endogenous neurite growth in differentiated NSCs, which may facilitate the application of NSC transplantation in ischemic stroke.
神经干细胞(NSC)移植已成为治疗脑缺血等神经疾病的一种有前途的方法。由于大多数外源性 NSC 产生的新细胞未能整合到缺血性大脑中并建立功能性突触网络,因此 NSC 移植治疗缺血性中风的神经功能恢复有限。在 NSC 分化过程中增强内源性神经突生长是促进突触网络的一种途径。磷酸酶和张力蛋白同源物(PTEN)作为一种肿瘤抑制因子,已被确定可调节成年中枢神经系统中的轴突生长。本研究旨在探讨 PTEN 在 NSC 分化过程中对神经突生长的作用。我们的结果表明,PTEN 的蛋白表达在 NSC 分化过程中显著增加,而磷酸化 S6 核糖体(p-S6R)的表达明显减少。在 NSCs 中用小干扰 RNA 敲低 PTEN 可以加速 NSC 分化过程中的神经突生长。这些结果表明 PTEN 抑制对 NSC 分化后神经元过程有显著影响,并确定了促进分化 NSCs 中内源性神经突生长的新途径,这可能有助于 NSC 移植在缺血性中风中的应用。