Author/Editor		Naviaux, Robert K.; Rogač, Mihael
Title		Antipurinergic therapy corrects the autism-like features in the poly(IC) mouse model
Type		članek
Vol. and No.		Letnik 8, št. 3
Publication year		2013
ISSN		1932-6203 - PloS one
Language		eng
Abstract		Background: Autism spectrum disorders (ASDs) are caused by both genetic and environmental factors. Mitochondria act toconnect genes and environment by regulating gene-encoded metabolic networks according to changes in the chemistry ofthe cell and its environment. Mitochondrial ATP and other metabolites are mitokinessignaling molecules made inmitochondriathat undergo regulated release from cells to communicate cellular health and danger to neighboring cellsvia 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) exposureand treatment with the non-selective purinergic antagonist suramin to test the role of purinergic signaling in C57BL/6Jmice. Results: We found that antipurinergic therapy (APT) corrected 16 multisystem abnormalities that defined the ASD-likephenotype 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 thehypothermia, metabolic, mitochondrial, P2Y2 and P2X7 purinergic receptor expression, and ERK1/2 and CAMKII signaltransduction 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 ofpathogenesis in autism and related spectrum disorders, and represents a fresh path forward for new drug development.
Keywords		Autism spectrum disorders (ASDs) antipurinergic therapy (APT)