title: Protection of TGF-β1 against neuroinflammation and neurodegeneration in Aβ1-42-induced Alzheimer's disease model rats.
abstract: Neuroinflammation has been reported to be associated with Alzheimer's disease (AD) pathogenesis. Neuroinflammation is generally considered as an outcome of glial activation; however, we recently demonstrated that T helper (Th)17 cells, a subpopulation of proinflammatory CD4+ T cells, are also involved in AD pathogenesis. Transforming growth factor (TGF)-β1, a cytokine that can be expressed in the brain, can be immunosuppressive, but its effects on lymphocyte-mediated neuroinflammation in AD pathogenesis have not been well addressed. In the current study we administered TGF-β1 via intracerebroventricle (ICV) and intranasal (IN) routes in AD model rats to investigate its antiinflammatory and neuroprotective effects. The AD rat model was prepared by bilateral hippocampal injection of amyloid-β (Aβ)1-42. TGF-β1 was administered via ICV one hour prior to Aβ1-42 injection or via both nares seven days after Aβ1-42 injection. ICV administration of TGF-β1 before Aβ1-42 injection remarkably ameliorated Aβ1-42-induced neurodegeneration and prevented Aβ1-42-induced increases in glia-derived proinflammatory mediators (TNF-α, IL-1β and iNOS), as well as T cell-derived proinflammatory cytokines (IFN-γ, IL-2, IL-17 and IL-22), in the hypothalamus, serum or cerebrospinal fluid (CSF) in a concentration-dependent manner. TGF-β1 pretreatment also prevented Aβ1-42-induced decreases in the neurotrophic factors, IGF-1, GDNF and BDNF, and in the antiinflammatory cytokine, IL-10. Similarly, IN administration of TGF-β1 after Aβ1-42 injection reduced neurodegeneration, elevation of proinflammatory mediators and cytokines, and reduction of neurotrophic and antiinflammatory factors, in the hypothalamus, serum or CSF. These findings suggest that TGF-β1 suppresses glial and T cell-mediated neuroinflammation and thereby alleviates AD-related neurodegeneration. The effectiveness of IN administered TGF-β1 in reducing Aβ1-42 neurotoxicity suggests a possible therapeutic approach in patients with AD.
authors: Department of Physiology, School of Medicine, and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China; Department of Neurology, Affiliated Hospital, Nantong University, Nantong, China.
authors: Jia-Hui
authors: JH
authors: Chen
authors: Department of Neurology, Affiliated Hospital, Nantong University, Nantong, China.
authors: Kai-Fu
authors: KF
authors: Ke
authors: Department of Physiology, School of Medicine, and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
authors: Jian-Hua
authors: JH
authors: Lu
authors: Department of Physiology, School of Medicine, and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
authors: Yi-Hua
authors: YH
authors: Qiu
authors: Department of Physiology, School of Medicine, and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
authors: Yu-Ping
authors: YP
authors: Peng
mesh_terms: D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007031:Hypothalamus / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control*; D007267:Injections; D009410:Nerve Degeneration / Q000473:pathology / Q000517:prevention & control; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D053773:Transforming Growth Factor beta1; C075222:amyloid beta-protein (1-42)