• Sheikh F Ahmad, Mushtaq A Ansari, Ahmed Nadeem, Saleh A Bakheet, Moureq R Alotaibi, Abdullah F Alasmari, Musaad A Alshammari, Haneen A Al-Mazroua, and Sabry M Attia.
• Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: fashaikh@ksu.edu.sa.
• Eur. J. Pharmacol. 2019 Mar 5; 846: 100-108.

AbstractAutism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by deficits in social interaction, communication, and repetitive behaviors. BTBR T+ Itpr3tf/J (BTBR) mice, a preclinical autistic model featuring ASD symptoms as defined by social relations, was used in this study. We evaluated the potentially protective effect of D-Ala-peptide T-amide (DAPTA), a selective C-C chemokine receptor 5 (CCR5) antagonist, in BTBR mice. CCR5 is considered a potential therapeutic target in different neurodegenerative disorders. BTBR and C57 mice were intraperitoneally (i.p) treated with the DAPTA (0.01 mg/kg, i.p, once daily) for 7 days. We examined the effect of DAPTA by evaluating marble burying and administering repetitive behavior tests. We employed flow cytometry to assess the effect of DAPTA on CCR5+, CD4+CCR5+, CCR5+IL-6+, CCR5+IL-9+, CCR5+IL-17A+, CCR5+RORγT+, CCR5+IL-10+, and CCR5+Foxp3+ in spleen cells. We further explored the effects of DAPTA on IL-6, IL-9, IL-17A, RORγT, IL-10, and Foxp3 protein and mRNA expression levels in the brain tissues. DAPTA administration significantly decreased marble burying and repetitive behavior in BTBR mice. Additionally, DAPTA treatment inhibited CCR5+, CD4+CCR5+, CCR5+IL-6+, CCR5+IL-9+, CCR5+IL-17A+, CCR5+RORγT+, and upregulated CCR5+IL-10+, and CCR5+Foxp3+ production. We further observed that DAPTA downregulated IL-6, IL-9, IL-17A, and RORγT, and increased IL-10 and Foxp3 protein and mRNA expression. Therefore, our results suggest that DAPTA administration represents a potential treatment strategy for patients with ASD.Copyright © 2019 Elsevier B.V. All rights reserved.

39 keywords...

hide…