Resveratrol Ameliorates Dysregulation of Th1, Th2, Th17, and T Regulatory Cell-Related Transcription Factor Signaling in a BTBR T + tf/J Mouse Model of Autism

• Published in: Molecular neurobiology 2017-09, Vol.54 (7), p.5201-5212
• Main Authors: Bakheet, Saleh A., Alzahrani, Mohammad Zeed, Ansari, Mushtaq Ahmad, Nadeem, Ahmed, Zoheir, Khairy M. A., Attia, Sabry M., AL-Ayadhi, Laila Yousef, Ahmad, Sheikh Fayaz
• Format: Article
• Language: English
• Subjects: Animals; Autism; Autistic Disorder - drug therapy; Autistic Disorder - immunology; Autistic Disorder - metabolism; Biomedical and Life Sciences; Biomedicine; Brain; CD4 antigen; Cell Biology; Cells; Disease Models, Animal; Drug therapy; Foxp3 protein; GATA-3 protein; Gene expression; Gene Expression Regulation - drug effects; Grooming; Helper cells; Inbreeding; Interleukin 17; Lymphocytes; Lymphocytes T; Mice; Mice, Transgenic; Neurobiology; Neurodegenerative diseases; Neurodevelopmental disorders; Neurology; Neurosciences; Resveratrol; Rodents; Social interactions; Spleen; Stilbenes - pharmacology; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Regulatory - drug effects; Tissues; Transcription factors; Transcription Factors - genetics
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-016-0066-1

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. It is characterized by impaired social communication, abnormal social interactions, and repetitive behaviors and/or restricted interests. BTBR T + tf/J (BTBR) inbred mice are commonly used as a model for ASD. Resveratrol is used widely as a beneficial therapeutic in the treatment of an extensive array of pathologies, including neurodegenerative diseases. In the present study, the effect of resveratrol administration (20 and 40 mg/kg) was evaluated in both BTBR and C57BL/6 (B6) mice. Behavioral (self-grooming), Foxp3, T-bet, GATA-3, RORγt, and IL-17A in CD4 + T cells were assessed. Our study showed that BTBR control mice exhibited a distinct immune profile from that of the B6 control mice. BTBR mice were characterized by lower levels of Foxp3 + and higher levels of RORγt + , T-bet + , and GATA-3 + production in CD4 + T cells when compared with B6 control. Resveratrol (20 and 40 mg/kg) treatment to B6 and BTBR mice showed substantial induction of Foxp3 + and reduction of T-bet + , GATA-3 + , and IL-17A + expression in CD4 + cells when compared with the respective control groups. Moreover, resveratrol treatment resulted in upregulated expression of Foxp3 mRNA and decreased expression levels of T-bet, GATA-3, RORγt, and IL-17A in the spleen and brain tissues. Western blot analysis confirmed that resveratrol treatment decreased the protein expression of T-bet, GATA-3, RORγ, and IL-17 and that it increased Foxp3 in B6 and BTBR mice. Our results suggest that autism is associated with dysregulation of transcription factor signaling that can be corrected by resveratrol treatment.