Abstract
BackgroundAccumulating evidence suggests that dysfunction in the glutamatergic system may underlie the pathophysiology of autism. The anterior cingulate cortex (ACC) has been implicated in autism as well as in glutamatergic neurotransmission. We hypothesized that alterations in the glutamate-glutamine cycle in the ACC might play a role in the pathophysiology of autism.MethodsWe performed Western blot analyses for the protein expression levels of enzymes in the glutamate-glutamine cycle, including glutamine synthetase, kidney-type glutaminase, liver-type glutaminase, and glutamate dehydrogenases 1 and 2, in the ACC of postmortem brain of individuals with autism (n = 7) and control subjects (n = 13).ResultsWe found that the protein levels of kidney-type glutaminase, but not those of the other enzymes measured, in the ACC were significantly lower in subjects with autism than in controls.ConclusionThe results suggest that reduced expression of kidney-type glutaminase may account for putative alterations in glutamatergic neurotransmission in the ACC in autism.
Highlights
Accumulating evidence suggests that dysfunction in the glutamatergic system may underlie the pathophysiology of autism
In a proton magnetic resonance spectroscopy (1H-MRS) study, Bernardi and colleagues [16] reported a reduction in Glx, a measure of the mixture of glutamate and glutamine, in the right anterior cingulate cortex (ACC) of adults with autism spectrum disorder (ASD), another 1H-MRS study revealed no such difference in Glx in the ACC of children with ASD [17]
To probe for direct evidence of any differences in the levels of glutamateglutamine cycle-related enzymes between the brain of individuals with autism and that of healthy subjects, we examined here the protein levels of the following enzymes associated with the glutamate-glutamine cycle in the postmortem brains of individuals with autism: glutamine synthetase (GS), which converts glutamate to glutamine; kidney-type glutaminase (KGA), which synthesizes glutamate from glutamine; liver-type glutaminase (LGA), which is an isozyme dominant in the liver; and glutamate dehydrogenases 1 (GDH1) and 2 (GDH2), both of which synthesize glutamate from α-ketoglutarate
Summary
Accumulating evidence suggests that dysfunction in the glutamatergic system may underlie the pathophysiology of autism. In a proton magnetic resonance spectroscopy (1H-MRS) study, Bernardi and colleagues [16] reported a reduction in Glx, a measure of the mixture of glutamate and glutamine, in the right ACC of adults with ASD, another 1H-MRS study revealed no such difference in Glx in the ACC of children with ASD [17]. Such inconsistent results might be attributable to differences in the age range of the subjects studied and/or in the resolution of the equipment used
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