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Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model
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 metabo...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596371/ https://www.ncbi.nlm.nih.gov/pubmed/23516405 http://dx.doi.org/10.1371/journal.pone.0057380 |
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author | Naviaux, Robert K. Zolkipli, Zarazuela Wang, Lin Nakayama, Tomohiro Naviaux, Jane C. Le, Thuy P. Schuchbauer, Michael A. Rogac, Mihael Tang, Qingbo Dugan, Laura L. Powell, Susan B. |
author_facet | Naviaux, Robert K. Zolkipli, Zarazuela Wang, Lin Nakayama, Tomohiro Naviaux, Jane C. Le, Thuy P. Schuchbauer, Michael A. Rogac, Mihael Tang, Qingbo Dugan, Laura L. Powell, Susan B. |
author_sort | Naviaux, Robert K. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3596371 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35963712013-03-20 Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model Naviaux, Robert K. Zolkipli, Zarazuela Wang, Lin Nakayama, Tomohiro Naviaux, Jane C. Le, Thuy P. Schuchbauer, Michael A. Rogac, Mihael Tang, Qingbo Dugan, Laura L. Powell, Susan B. PLoS One Research Article 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. Public Library of Science 2013-03-13 /pmc/articles/PMC3596371/ /pubmed/23516405 http://dx.doi.org/10.1371/journal.pone.0057380 Text en © 2013 Naviaux et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Naviaux, Robert K. Zolkipli, Zarazuela Wang, Lin Nakayama, Tomohiro Naviaux, Jane C. Le, Thuy P. Schuchbauer, Michael A. Rogac, Mihael Tang, Qingbo Dugan, Laura L. Powell, Susan B. Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model |
title | Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model |
title_full | Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model |
title_fullStr | Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model |
title_full_unstemmed | Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model |
title_short | Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model |
title_sort | antipurinergic therapy corrects the autism-like features in the poly(ic) mouse model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596371/ https://www.ncbi.nlm.nih.gov/pubmed/23516405 http://dx.doi.org/10.1371/journal.pone.0057380 |
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