title: TGF-β1 protection against Aβ1-42-induced neuroinflammation and neurodegeneration in rats.
abstract: 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 Aβ1-42 injection in both sides of the hippocampus, to show the neuroprotection of TGF-β1. The TGF-β1 administration after the Aβ1-42 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 Aβ1-42 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.
authors.affiliation: School of Biological & Basic Medical Sciences, Soochow University, 199 Renai Road, Suzhou 215123, China. swx@ntu.edu.cn.
authors.forename: Wei-Xing
authors.initials: WX
authors.lastname: Shen
authors.affiliation: Department of Physiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China. liuzhan8301@163.com.
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Physiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China. ljhua@ntu.edu.cn.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Lu
authors.affiliation: Department of Physiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China. yppeng@ntu.edu.cn.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Peng
authors.affiliation: Department of Physiology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China. yhqiu@ntu.edu.cn.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Qiu
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000134:cerebrospinal fluid; D015536:Down-Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007031:Hypothalamus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D009410:Nerve Degeneration / Q000097:blood / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D053773:Transforming Growth Factor beta1; C075222:amyloid beta-protein (1-42)