Enriched environment treatment promotes neurofunctional recovery by regulating the ALK5/Smad2/3/Gadd45β signaling pathway in rats with cerebral ischemia /reperfusion injury

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemistry international Pub Date : 2024-07-18 DOI:10.1016/j.neuint.2024.105806

Gang Liu , Chenchen Xie , Jiani Li , Xia Jiang , Hao Tang , Changqing Li , Keming Zhang

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引用次数: 0

Abstract

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.

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富集环境通过调节 ALK5/Smad2/3/Gadd45β 信号通路促进脑缺血再灌注损伤大鼠的神经功能恢复

研究表明，富集环境（EE）治疗可改变神经退行性疾病的神经可塑性。然而，EE 治疗在缺血性中风中的作用仍不清楚。之前的研究发现，EE 治疗可促进脑缺血/再灌注（I/R）损伤后脑活化素受体样激酶-5（ALK5）的表达。ALK5 通过调节 Smad2/3 和 Gadd45β 被认为是神经可塑性的潜在介质。因此，本研究旨在探讨 EE 治疗是否能通过调节 ALK5/Smad2/3/Gadd45β 通路促进神经功能恢复。研究利用大鼠大脑中动脉闭塞/再灌注（MCAO/R）模型。研究采用Western印迹（WB）技术评估了ALK5/Smad2/3/Gadd45β信号通路的变化。脑损伤通过梗死体积和神经行为评分进行评估。使用双皮质素（DCX）和Nestin评估EE治疗对神经发生的影响，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-考克斯染色评估树突可塑性。研究表明，EE治疗可通过调节ALK5的表达来调节Smad2/3/Gadd45β通路。EE治疗对脑梗塞体积、神经功能、新生神经元、脑I/R损伤后树突和轴突可塑性的保护作用被ALK5沉默所抵消。EE治疗可增强脑I/R损伤后的神经功能恢复，而这是通过调节ALK5/Smad2/3/Gadd45β信号通路促进神经可塑性实现的。

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来源期刊

Neurochemistry international 医学-神经科学

CiteScore

8.40

自引率

2.40%

发文量

128

审稿时长

37 days

期刊介绍： Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.