Abstract
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.
Highlights
Using RT-qPCR and western blotting, we investigated the effect of 5-AIQ on expression levels of FOXP3 Messenger RNA (mRNA) and protein in brain tissue
The mRNA and protein levels of Helios in the brain tissue of BTBR mice were decreased in comparison with those of C57 mice and were significantly upregulated in brain tissue of 5-AIQ-treated BTBR mice (Figure 2C,D)
Our study has provided several pieces of evidence that address the pivotal role of Poly(ADP-ribose) polymerase-1 (PARP)-1 inhibition in the mouse autism model
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Autism spectrum disorders (ASD) cover a range of common neurobehavioral disorders characterized by impairments in social interaction and verbal and nonverbal communication, and stereotyped patterns of behaviors and reciprocal social interaction [1]. The pathogenesis of ASD remains unclear, but immune dysfunction has been suggested as a major etiological component associated with ASD pathophysiology [2]. Several genetic studies linked ASD with genes that are involved with various immune functions [3,4]. Immunological abnormalities have been reported in children with
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