BACKGROUND: Autism spectrum disorders (ASDs) are caused by both genetic and 
environmental factors. Mitochondria act to connect genes and environment by 
regulating gene-encoded metabolic networks according to changes in the chemistry 
of the cell and its environment. Mitochondrial ATP and other metabolites are 
mitokines-signaling molecules made in mitochondria-that undergo regulated 
release from cells to communicate cellular health and danger to neighboring 
cells via purinergic signaling. The role of purinergic signaling has not yet 
been explored in autism spectrum disorders.
OBJECTIVES AND METHODS: We used the maternal immune activation (MIA) mouse model 
of gestational poly(IC) exposure and treatment with the non-selective purinergic 
antagonist suramin to test the role of purinergic signaling in C57BL/6J mice.
RESULTS: We found that antipurinergic therapy (APT) corrected 16 multisystem 
abnormalities that defined the ASD-like phenotype in this model. These included 
correction of the core social deficits and sensorimotor coordination 
abnormalities, prevention of cerebellar Purkinje cell loss, correction of the 
ultrastructural synaptic dysmorphology, and correction of the hypothermia, 
metabolic, mitochondrial, P2Y2 and P2X7 purinergic receptor expression, and 
ERK1/2 and CAMKII signal transduction abnormalities.
CONCLUSIONS: Hyperpurinergia is a fundamental and treatable feature of the 
multisystem abnormalities in the poly(IC) mouse model of autism spectrum 
disorders. Antipurinergic therapy provides a new tool for refining current 
concepts of pathogenesis in autism and related spectrum disorders, and 
represents a fresh path forward for new drug development.