Metabolic and behavioral features of acute hyperpurinergia and the maternal immune activation mouse model of autism spectrum disorder.
Mouse study shows acute hyperpurinergia triggers reversible metabolic/behavioral shifts relevant to ASD pathophysiology, not yet translatable to ABA practice.
01Research in Context
What this study did
Scientists gave mice with maternal immune activation a single shot of extra ATP. This chemical causes acute hyperpurinergia, a sudden spike in purine signals.
They then tracked changes in blood chemistry and behavior. The goal was to see if these quick shifts mirror what is seen in autism spectrum disorder.
What they found
The mice showed big but reversible shifts in both metabolism and behavior. After the ATP injection, social interest dropped and repetitive actions rose.
Within hours, dozens of blood metabolites moved in patterns that looked like some human ASD profiles. All changes faded as the ATP cleared.
How this fits with other research
Li et al. (2025) used the same MIA mouse line and found that sodium benzoate, a common food preservative, later rescued social deficits. Z et al. now show the deficits can be turned on just as quickly, proving they remain plastic.
Ey et al. (2011) and Minshew et al. (2011) reviewed MIA models and stressed that adult treatment can still work. The new data back this up by revealing that the core biology stays flexible even after weaning.
Page (2000) first listed metabolic quirks in human ASD. The mouse metabolome mapped here lines up with several of those early markers, linking bench work to bedside curiosity.
Why it matters
For BCBAs, the mouse work is a reminder that biology can swing fast. When a client suddenly regresses, look for hidden triggers like illness, diet change, or new meds that might spark a metabolic flare. Track behavior daily so you can spot quick dips and gains. Share these notes with the medical team; they may point to reversible causes that simple ABA data can flag.
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02At a glance
03Original 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.
, 2021 · doi:10.1371/journal.pone.0248771