Cette étude a étudié l'influence de l'activité du récepteur A2A de l'adénosine sur les récepteurs de chimiokines C-C et C-X-C impliqués dans l'autisme dans le modèle de souris BTBR.
résultats suggèrent que le traitement des souris BTBR avec CGS (agoniste du récepteur A2A CGS21680) diminue la signalisation des récepteurs de chimiokine C-C et C-X-C et pourrait donc constituer une avenue unique pour développer de futures thérapies pour l'autisme et les troubles neuro-immunologiques.
Mol Neurobiol. 2017 Apr 18. doi: 10.1007/s12035-017-0548-9.
Immune Alterations in CD8+ T Cells Are Associated with Neuronal C-C and C-X-C Chemokine Receptor Regulation Through Adenosine A2A Receptor Signaling in a BTBR T+ Itpr3tf/J Autistic Mouse Model
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia. email@example.com.
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
- Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.
Associative studies on a range of neurodevelopmental disorders have identified relationships between behavioral deficits and immune system function. The BTBR T+ Itpr3tf/J (BTBR) mouse strain displays aberrant characteristics in its social behavior and immune responses, providing a significant opportunity to examine the relationship between behavior and the immune system. This study investigated the influence of adenosine A2A receptor activity on C-C and C-X-C chemokine receptors involved in autism in the BTBR mouse model. A2A receptors have previously been targeted in clinical trials by potential therapeutics with neuroprotective, immunomodulatory, and analgesic properties. In this study, we examined the effects of A2A receptor antagonist SCH5826 (SCH) and A2A receptor agonist CGS21680 (CGS) on C-C and C-X-C chemokine receptors (CCR3, CCR4, CCR5, CCR6, CCR7, CXCR3, CXCR4, and CXCR5) on splenic CD8+ T cells in the BTBR autistic mouse model. We also assessed the C-C and C-X-C chemokine receptors mRNA levels in brain tissue. Our results showed that CCR3+, CCR4+, CCR5+, CCR6+, CCR7+, CXCR3+, CXCR4+, and CXCR5+ production in splenic CD8+ T cells decreased significantly in BTBR-CGS-treated mice in comparison with that in BTBR control and BTBR-SCH-treated mice. In addition, RT-PCR analysis revealed decreased gene expression levels for C-C and C-X-C chemokine receptors in the brain tissue of BTBR-CGS-treated mice, whereas these levels were significantly increased in BTBR control and BTBR-SCH-treated mice. Our results suggest that treating BTBR mice with CGS decreases C-C and C-X-C chemokine receptor signaling and might therefore provide a unique avenue for developing future therapies for autism and neuroimmunological disorders.
- PMID: 28421534
- DOI: 10.1007/s12035-017-0548-9