Protection of TGF-β1 against neuroinflammation and neurodegeneration in Aβ1-42-induced Alzheimer's disease model rats
| Autor: | Yu-Ping Peng, Jia-Hui Chen, Kai-Fu Ke, Jian-Hua Lu, Yi-Hua Qiu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_treatment
Anti-Inflammatory Agents Hypothalamus lcsh:Medicine Pharmacology Neuroprotection Proinflammatory cytokine Injections Rats Sprague-Dawley Transforming Growth Factor beta1 Neurotrophic factors Alzheimer Disease Glial cell line-derived neurotrophic factor Medicine Animals lcsh:Science Neuroinflammation Administration Intranasal Inflammation Multidisciplinary Amyloid beta-Peptides biology business.industry Neurodegeneration lcsh:R Neurotoxicity medicine.disease Peptide Fragments Rats Disease Models Animal Cytokine Neuroprotective Agents Immunology Nerve Degeneration biology.protein Cytokines lcsh:Q business Neuroglia Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 2, p e0116549 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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