Aperçu: G.M.
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
Ahmad SF1, Ansari MA2, Nadeem A2, Bakheet SA2, Mohammad R3, Attia SM2,4.
Author information
- 1
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia. s_fayazahmad@yahoo.com.
- 2
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
- 3
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
- 4
- Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.
Abstract
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
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