Resveratrol attenuates pro-inflammatory cytokines and activation of JAK1-STAT3 in BTBR T + Itpr3 tf /J autistic mice
| Autor: | Wael A. Alanazi, Abdullah F. Alasmari, Saleh A. Bakheet, Ahmed Nadeem, Sabry M. Attia, Musaad A. Alshammari, Mohammad Z. Alzahrani, Mushtaq A. Ansari, Sheikh F. Ahmad |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Spleen Resveratrol Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neurodevelopmental disorder Internal medicine medicine STAT3 Pharmacology biology business.industry medicine.disease 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry biology.protein Phosphorylation Autism Signal transduction business 030217 neurology & neurosurgery |
| Zdroj: | European Journal of Pharmacology. 829:70-78 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2018.04.008 |
| Popis: | Autism is a neurodevelopmental disorder characterized by qualitative impairment in communication, social interaction, and repetitive stereotypic behavior. Resveratrol plays a role in several disorders such as neuroimmune, autoimmune, and allergic disorders. BTBR T+ Itpr3tf/J (BTBR) mice, a model for autism, show several behavioral deficits that are physiological characteristics similar to those observed in patients with autism. Previous studies have shown that JAK-STAT signaling pathway is associated with many neurodevelopmental disorders. We investigated the possible role of resveratrol on IL-6+, TNF-α+, IFN-γ+, and STAT3+ in CD4+ T spleen cells in BTBR mice as compared to C57BL/6J mice. We also assessed the effect of resveratrol treatment on IL-6, TNF-α, IFN-γ, JAK1, and STAT3 mRNA expression levels in the brain tissue. We further assessed IL-6, IFN-γ, TNF-α, phosphorylated (p) JAK1, and pSTAT3 (Tyr705) protein expression levels in the brain tissue. Resveratrol (20 and 40 mg/kg)-treated mice had significantly decreased in IL-6+, TNF-α+, IFN-γ+, and STAT3+ in CD4+ spleen cells as compared with BTBR control mice. Resveratrol treatment also decreased IL-6, TNF-α, IFN-γ, JAK1, and STAT3 mRNA expression levels as compared with BTBR control mice in the brain tissue. Moreover, resveratrol treatment resulted in decreased protein expression levels of IL-6, IFN-γ, TNF-α, pJAK1, and pSTAT3 (Tyr705) as compared with BTBR control mice in the brain tissues. Taken together, these results indicate the efficacy of resveratrol in reducing cytokines and JAK-1/STAT3 signaling in BTBR mice, which is a novel and important finding and might be important for future therapies in neuroimmune dysfunction. |
| Databáze: | OpenAIRE |
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