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.
Khaled AlhosainiMushtaq A AnsariAhmed NadeemSaleh A BakheetSabry M AttiaKhalid AlhazzaniThamer H AlbekairiHaneen A Al-MazrouaHafiz M MahmoodSheikh F AhmadPublished in: Brain sciences (2021)
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.
Keyphrases
- autism spectrum disorder
- poor prognosis
- induced apoptosis
- transcription factor
- regulatory t cells
- mouse model
- oxidative stress
- signaling pathway
- intellectual disability
- south africa
- cell proliferation
- flow cytometry
- adipose tissue
- dna damage
- metabolic syndrome
- mental health
- immune response
- anti inflammatory
- high fat diet induced
- high resolution
- attention deficit hyperactivity disorder
- brain injury
- long non coding rna
- insulin resistance
- endoplasmic reticulum stress
- white matter
- resting state
- blood brain barrier
- subarachnoid hemorrhage