TGF-β1 Protection against Aβ1–42-Induced Neuroinflammation and Neurodegeneration in Rats

International Journal of Molecular Sciences

Wei-Xing Shen¹  Jia-Hui Chen²  Jian-Hua Lu²  Yu-Ping Peng²  Yi-Hua Qiu² 

[1] School of Biological & Basic Medical Sciences, Soochow University, 199 Renai Road, Suzhou 215123, China; E-Mail:;Department of Physiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China; E-Mails:

关键词: TGF-β1;    Alzheimer’s disease;    Aβ_1–42;    T-lymphocytes;    microglia;   

DOI  :  10.3390/ijms151222092

来源: mdpi

【 摘 要 】

Transforming growth factor (TGF)-β1, a cytokine that can be expressed in the brain, is a key regulator of the brain’s responses to injury and inflammation. Alzheimer’s disease (AD), the most common neurodegenerative disorder, involves inflammatory processes in the brain in addition to the hallmarks, amyloid-β (Aβ) plaques and neurofibrillary tangles. Recently, we have shown that T-helper (Th) 17 cells, a subpopulation of CD4⁺ T-cells with high proinflammation, also participate in the brain inflammatory process of AD. However, it is poorly known whether TGF-β1 ameliorates the lymphocyte-mediated neuroinflammation and, thereby, alleviates neurodegeneration in AD. Herein, we administered TGF-β1 via the intracerebroventricle (ICV) in AD model rats, by Aβ_1–42 injection in both sides of the hippocampus, to show the neuroprotection of TGF-β1. The TGF-β1 administration after the Aβ_1–42 injection ameliorated cognitive deficit and neuronal loss and apoptosis, reduced amyloid precursor protein (APP) expression, elevated protein phosphatase (PP)2A expression, attenuated glial activation and alleviated the imbalance of the pro-inflammatory/anti-inflammatory responses of T-lymphocytes, compared to the Aβ_1–42 injection alone. These findings demonstrate that TGF-β1 provides protection against AD neurodegeneration and suggest that the TGF-β1 neuroprotection is implemented by the alleviation of glial and T-cell-mediated neuroinflammation.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.