Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Neurology, Affiliated Hospital & Clinical Medical College of Chengdu University, Chengdu, Sichuan Province, China; Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Neurochem Int. 2024 Sep;178:105806. doi: 10.1016/j.neuint.2024.105806. Epub 2024 Jul 18.
It has been demonstrated that an enriched environment (EE) treatment can alter neuroplasticity in neurodegenerative diseases. However, the role of EE treatment in ischemic stroke remains unclear. Previous findings have revealed that EE treatment can promote cerebral activin-receptor-like-kinase-5 (ALK5) expression after cerebral ischemia/reperfusion (I/R) injury. ALK5 has been identified as a potential mediator of neuroplasticity through its modulation of Smad2/3 and Gadd45β. Therefore, the aim of this study was to investigate whether EE treatment could promote neurofunctional recovery by regulating the ALK5/Smad2/3/Gadd45β pathway. The study utilized the rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). The ALK5/Smad2/3/Gadd45β signaling pathway changes were evaluated using western blotting (WB). Brain injury was assessed by infarct volume and neurobehavioral scores. The effect of EE treatment on neurogenesis was evaluated using Doublecortin (DCX) and Nestin, axonal plasticity with biotinylated dextran amine (BDA) nerve tracing, and dendritic plasticity was assessed using Golgi-Cox staining. EE treatment has been demonstrated to modulate the Smad2/3/Gadd45β pathway by regulating the expression of ALK5. The protective effects of EE treatment on brain infarct volume, neurological function, newborn neurons, dendritic and axonal plasticity following cerebral I/R injury were counteracted by ALK5 silencing. EE treatment can enhance neurofunctional recovery after cerebral I/R injury, which is achieved by regulating the ALK5/Smad2/3/Gadd45β signaling pathway to promote neuroplasticity.
已证实，丰富环境（EE）处理可改变神经退行性疾病中的神经可塑性。然而，EE 处理在缺血性中风中的作用尚不清楚。先前的研究结果表明，EE 处理可促进脑缺血/再灌注（I/R）损伤后的激活素受体样激酶-5（ALK5）表达。ALK5 已被确定为神经可塑性的潜在介质，通过其对 Smad2/3 和 Gadd45β 的调节。因此，本研究旨在探讨 EE 处理是否通过调节 ALK5/Smad2/3/Gadd45β 通路促进神经功能恢复。该研究使用大脑中动脉闭塞/再灌注（MCAO/R）大鼠模型。通过 Western blot（WB）评估 ALK5/Smad2/3/Gadd45β 信号通路的变化。通过梗塞体积和神经行为评分评估脑损伤。使用 Doublecortin（DCX）和 Nestin 评估 EE 处理对神经发生的影响，使用生物素化葡聚糖胺（BDA）神经追踪评估轴突可塑性，使用高尔基染色评估树突可塑性。EE 处理通过调节 ALK5 的表达来调节 Smad2/3/Gadd45β 通路。ALK5 沉默可拮抗 EE 处理对脑 I/R 损伤后脑梗塞体积、神经功能、新生神经元、树突和轴突可塑性的保护作用。EE 处理可以通过调节 ALK5/Smad2/3/Gadd45β 信号通路促进神经可塑性，增强脑 I/R 损伤后的神经功能恢复。
