Molecular Neurobiology

, Volume 54, Issue 7, pp 5201–5212 | Cite as

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

  • Saleh A. Bakheet
  • Mohammad Zeed Alzahrani
  • Mushtaq Ahmad Ansari
  • Ahmed Nadeem
  • Khairy M. A. Zoheir
  • Sabry M. Attia
  • Laila Yousef AL-Ayadhi
  • Sheikh Fayaz AhmadEmail author


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.


Autism Resveratrol BTBR T + tf/J, C57BL/6 J Transcription factors CD4 cells 



Autism spectrum disorder


Cluster of differentiation 4

Th cells

T helper cells




Forkhead box P3


Signal transducer and activator of transcription 3


retinoid-acid receptor-related orphan receptor gamma t


T-box transcription factor


GATA binding protein 3


Messenger RNA


Reverse transcription polymerase chain reaction








Dimethyl sulfoxide


Central nervous system



The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding the work through the research group project No. RGP-VPP-120.

Compliance with Ethical Standards

All procedures were performed with the approval of the Institutional Animal Care and Use Committee.

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Saleh A. Bakheet
    • 1
  • Mohammad Zeed Alzahrani
    • 1
  • Mushtaq Ahmad Ansari
    • 1
  • Ahmed Nadeem
    • 1
  • Khairy M. A. Zoheir
    • 1
    • 2
  • Sabry M. Attia
    • 1
    • 3
  • Laila Yousef AL-Ayadhi
    • 4
  • Sheikh Fayaz Ahmad
    • 1
    Email author
  1. 1.Department of Pharmacology and Toxicology, College of PharmacyKing Saud UniversityRiyadhKingdom of Saudi Arabia
  2. 2.Department of Cell BiologyNational Research CentreCairoEgypt
  3. 3.Department of Pharmacology and Toxicology, College of PharmacyAl-Azhar UniversityCairoEgypt
  4. 4.Autism Research and Treatment Center, AL-Amodi Autism Research Chair, Department of Physiology, College of MedicineKing Saud UniversityRiyadhKingdom of Saudi Arabia

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