Antipurinergic therapy corrects the autism-like features in the Fragile X (Fmr1 knockout) mouse model

Jane C. Naviaux, Lin Wang, Kefeng Li, A. Taylor Bright, William A. Alaynick, Kenneth R. Williams, Susan B. Powell, Robert K. Naviaux

研究成果: Article同行評審

68 引文 斯高帕斯(Scopus)

摘要

Background: This study was designed to test a new approach to drug treatment of autism spectrum disorders (ASDs) in the Fragile X (Fmr1) knockout mouse model. Methods: We used behavioral analysis, mass spectrometry, metabolomics, electron microscopy, and western analysis to test the hypothesis that the disturbances in social behavior, novelty preference, metabolism, and synapse structure are treatable with antipurinergic therapy (APT). Results: Weekly treatment with the purinergic antagonist suramin (20 mg/kg intraperitoneally), started at 9 weeks of age, restored normal social behavior, and improved metabolism, and brain synaptosomal structure. Abnormalities in synaptosomal glutamate, endocannabinoid, purinergic, and IP3 receptor expression, complement C1q, TDP43, and amyloid β precursor protein (APP) were corrected. Comprehensive metabolomic analysis identified 20 biochemical pathways associated with symptom improvements. Seventeen pathways were shared with human ASD, and 11 were shared with the maternal immune activation (MIA) model of ASD. These metabolic pathways were previously identified as functionally related mediators of the evolutionarily conserved cell danger response (CDR). Conclusions: The data show that antipurinergic therapy improves the multisystem, ASD-like features of both the environmental MIA, and the genetic Fragile X models.

原文English
文章編號1
期刊Molecular Autism
6
發行號1
DOIs
出版狀態Published - 2015
對外發佈

指紋

深入研究「Antipurinergic therapy corrects the autism-like features in the Fragile X (Fmr1 knockout) mouse model」主題。共同形成了獨特的指紋。

引用此