Resveratrol treatment attenuates chemokine receptor expression in the BTBR T+tf/J mouse model of autism.
Autism is a neurodevelopmental disorder categorized by qualitative impairments in social interaction, communication, and repetitive stereotypic behavior. Emerging evidence increasingly suggests that chemokine receptors have a pivotal role in the central nervous system and are involved in the pathogenesis of numerous neuroinflammatory diseases. Resveratrol is widely used to treat neurodegenerative diseases, but its effect on autism has not been investigated. We investigated the effect of resveratrol (20 and 40mg/kg) in the spleen and brain tissues of BTBR T+tf/J (BTBR) and C57BL/6J (B6) mice as well as on the C-C chemokine receptor (CCR) and C-X-C motif chemokine receptor (CXCR) (CCR3+, CCR5+, CCR7+and CCR9+, CXCR3+and CXCR5+) in cluster of differentiation 4-positive (CD4+) T cells in the spleen. We also assessed the mRNA expression of CCR and CXCR receptors in the spleen and brain tissues. Our study revealed that the BTBR and B6 control mice showed different immune profiles. The BTBR mice showed characteristic higher levels of both CCR and CXCR production and expression in CD4+T cells than the B6 control mice did. Treatment of B6 and BTBR mice with resveratrol (20 and 40mg/kg) induced a substantial decrease in the CCR and CXCR production and expression in CD4+T cells compared with the respective untreated control groups. Moreover, resveratrol treatment decreased the mRNA expression levels of CCR and CXCR in the spleen and brain tissues. Resveratrol downregulated the chemokine receptor levels, which might provide unique targets for future therapies for autism.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Saleh A
SA
Bakheet
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Mohammad Zeed
MZ
Alzahrani
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Ahmed
A
Nadeem
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Mushtaq Ahmad
MA
Ansari
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Department of Cell Biology, National Research Center, Cairo, Egypt.
Khairy M A
KMA
Zoheir
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.
Sabry M
SM
Attia
Autism Research and Treatment Center, AL-Amodi Autism Research Chair, Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Laila Yousef
LY
Al-Ayadhi
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: s_fayazahmad@yahoo.com.
Sheikh Fayaz
SF
Ahmad
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001321:Autistic Disorder / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D000077185:Resveratrol; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D013267:Stilbenes; D000077185:Resveratrol
Autism; BTBR T+tf/J; Brain; C57BL/6J; CCR and CXCR; Resveratrol; Spleen