5-Aminoisoquinolinone, a PARP-1 Inhibitor, Ameliorates Immune Abnormalities through Upregulation of Anti-Inflammatory and Downregulation of Inflammatory Parameters in T Cells of BTBR Mouse Model of Autism

被引：17

作者：

Alhosaini, Khaled ^{[1
]}

Ansari, Mushtaq A. ^{[1
]}

Nadeem, Ahmed ^{[1
]}

Bakheet, Saleh A. ^{[1
]}

Attia, Sabry M. ^{[1
]}

Alhazzani, Khalid ^{[1
]}

Albekairi, Thamer H. ^{[1
]}

Al-Mazroua, Haneen A. ^{[1
]}

Mahmood, Hafiz M. ^{[1
]}

Ahmad, Sheikh F. ^{[1
]}

机构：

[1] King Saud Univ, Coll Pharm, Dept Pharmacol & Toxicol, Riyadh 11451, Saudi Arabia

来源：

BRAIN SCIENCES | 2021年 / 11卷 / 02期

关键词：

autism; BTBR mice; 5-AIQ; cytokines; transcription factors; spleen and brain tissue; POLY(ADP-RIBOSE) POLYMERASE-1 INHIBITOR; LYMPHOCYTE CYTOKINE PROFILES; HELPER; 9; CELLS; TRANSCRIPTION FACTORS; PERIPHERAL-BLOOD; SOCIAL-BEHAVIOR; NITRIC-OXIDE; RISK-FACTOR; TH17; ACTIVATION;

D O I：

10.3390/brainsci11020249

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Autism spectrum disorder (ASD) covers a range of neurodevelopmental disorders involving impairments in communication and repetitive and stereotyped patterns of behavior and reciprocal social interaction. 5-Aminoisoquinolinone (5-AIQ), a PARP-1 inhibitor, has neuroprotective and anti-inflammatory effects. We investigated the influence of 5-AIQ-treatment in BTBR T+ Itpr3tf/J (BTBR) mice as an autism model and used flow cytometry to assess the effect of 5-AIQ on FOXP3, Helios, GATA3, IL-9, IL-10 and IL-17A production by CXCR6+ and CD4+ T cells in the spleen. We also confirmed the effect of 5-AIQ treatment on expression of FOXP3, Helios, GATA3, IL-17A, IL-10, and IL-9 mRNA and protein expression levels in the brain tissue by quantitative PCR and western blotting. Our results demonstrated that 5-AIQ-treated BTBR mice had significantly increased numbers of CXCR6+FOXP3+, CXCR6+IL-10+, and CXCR6+Helios+ cells and decreased numbers of CD4+GATA3+, CD4+IL-9+, and CD4+IL-17A+ cells as compared with those in untreated BTBR mice. Our results further demonstrated that treatment with 5-AIQ in BTBR mice increased expression for FOXP3, IL-10, and Helios, and decreased expression for GATA3, IL-17A, and IL-9 mRNA. Our findings support the hypotheses that 5-AIQ has promising novel therapeutic effects on neuroimmune dysfunction in autism and is associated with modulation of Treg and Th17 cells.

引用

页码：1 / 16

页数：16

共 72 条

[1] 5-aminoisoquinolinone attenuates social behavior deficits and immune abnormalities in the BTBR T+ Itpr3tf/J mouse model for autism [J].