5-aminoisoquinolinone attenuates social behavior deficits and immune abnormalities in the BTBR T + Itpr3 tf /J mouse model for autism.

Autor: Ahmad SF; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: fashaikh@ksu.edu.sa., Ansari MA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Nadeem A; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Bakheet SA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alqahtani F; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alhoshani AR; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alasmari F; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alsaleh NB; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Attia SM; 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.
Jazyk: angličtina
Zdroj: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2020 Feb; Vol. 189, pp. 172859. Date of Electronic Publication: 2020 Jan 23.
DOI: 10.1016/j.pbb.2020.172859
Abstrakt: Autism spectrum disorder (ASD) is diagnosed by core symptoms including impaired social communication and the presence of repetitive and stereotypical behaviors. There is also evidence for immune dysfunction in individuals with ASD, but it is a disease that is still insufficiently controlled by current treatment strategies. The use of 5-aminoisoquinolinone (5-AIQ) ameliorates several immune-mediated symptoms including rheumatoid arthritis and colitis, and has neuroprotective properties; however, its role in ASD is not yet characterized. In this study, we investigated the effect of 5-AIQ on sociability tests, self-grooming, marble burying, and locomotor activities in BTBR T + Itpr3tf/J (BTBR) mice, which serve as an ASD animal model. We further investigated the possible molecular mechanism of 5-AIQ administration on CXCR4-, CXCR6-, IFN-γ-, IL-22-, NOS2-, STAT1-, T-bet-, and RORγT-producing CD3 + T cells isolated from the spleens of treated mice. We also explored its effects on mRNA expression in brain tissue. Our results showed that in BTBR mice, 5-AIQ treatment significantly prevented self-grooming and marble burying behaviors and enhanced social interactions without any adverse effects on locomotor activity/anxiety level. Additionally, 5-AIQ treatment substantially decreased CXCR4-, CXCR6-, IFN-γ-, IL-22-, NOS2-, STAT1-, T-bet-, and RORγT-producing CD3 + T cells in the spleen. Furthermore, 5-AIQ treatment decreased CXCR4, IFN-γ, IL-22, STAT1, and RORγT mRNA expression levels in brain tissue. Our findings demonstrated that 5-AIQ improved behavioral and immune abnormalities associated with ASD, which supports the hypothesis that 5-AIQ has important therapeutic potential for the treatment of behavioral and neuroimmune dysfunctions in ASD.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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