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PLoS One

Title:		Metabolic and behavioral features of acute hyperpurinergia and the maternal immune activation mouse model of autism spectrum disorder
Author(s):		Zolkipli-Cunningham Z; Naviaux JC; Nakayama T; Hirsch CM; Monk JM; Li K; Wang L; Le TP; Meinardi S; Blake DR; Naviaux RK;
Address:		"The Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine, San Diego, CA, United States of America. Department of Neurosciences, University of California, San Diego School of Medicine, San Diego, CA, United States of America. Department of Chemistry, University of California, Irvine (UCI), Irvine, CA, United States of America. Department of Medicine, University of California, San Diego School of Medicine, San Diego, CA, United States of America. Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, CA, United States of America. Department of Pathology, University of California, San Diego School of Medicine, San Diego, CA, United States of America"
Journal Title:		PLoS One
Year:		2021
Volume:		20210318
Issue:		3
Page Number:		e0248771 -
DOI:		10.1371/journal.pone.0248771
ISSN/ISBN:		1932-6203 (Electronic) 1932-6203 (Linking)
Abstract:		"Since 2012, studies in mice, rats, and humans have suggested that abnormalities in purinergic signaling may be a final common pathway for many genetic and environmental causes of autism spectrum disorder (ASD). The current study in mice was conducted to characterize the bioenergetic, metabolomic, breathomic, and behavioral features of acute hyperpurinergia triggered by systemic injection of the purinergic agonist and danger signal, extracellular ATP (eATP). Responses were studied in C57BL/6J mice in the maternal immune activation (MIA) model and controls. Basal metabolic rates and locomotor activity were measured in CLAMS cages. Plasma metabolomics measured 401 metabolites. Breathomics measured 98 volatile organic compounds. Intraperitoneal eATP dropped basal metabolic rate measured by whole body oxygen consumption by 74% +/- 6% (mean +/- SEM) and rectal temperature by 6.2 +/- 0.3 C in 30 minutes. Over 200 metabolites from 37 different biochemical pathways where changed. Breathomics showed an increase in exhaled carbon monoxide, dimethylsulfide, and isoprene. Metabolomics revealed an acute increase in lactate, citrate, purines, urea, dopamine, eicosanoids, microbiome metabolites, oxidized glutathione, thiamine, niacinamide, and pyridoxic acid, and decreased folate-methylation-1-carbon intermediates, amino acids, short and medium chain acyl-carnitines, phospholipids, ceramides, sphingomyelins, cholesterol, bile acids, and vitamin D similar to some children with ASD. MIA animals were hypersensitive to postnatal exposure to eATP or poly(IC), which produced a rebound increase in body temperature that lasted several weeks before returning to baseline. Acute hyperpurinergia produced metabolic and behavioral changes in mice. The behaviors and metabolic changes produced by ATP injection were associated with mitochondrial functional changes that were profound but reversible"
Keywords:		"Acute Disease Adenosine Triphosphate/metabolism Animals Autism Spectrum Disorder/*metabolism *Behavior, Animal Body Temperature Chemokines/metabolism Corticosterone/metabolism Disease Models, Animal Energy Metabolism *Metabolomics Mice, Inbred C57BL Mitoc;neuroscience;"
Notes:		"MedlineZolkipli-Cunningham, Zarazuela Naviaux, Jane C Nakayama, Tomohiro Hirsch, Charlotte M Monk, Jonathan M Li, Kefeng Wang, Lin Le, Thuy P Meinardi, Simone Blake, Donald R Naviaux, Robert K eng U54 NS078059/NS/NINDS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2021/03/19 PLoS One. 2021 Mar 18; 16(3):e0248771. doi: 10.1371/journal.pone.0248771. eCollection 2021"