Decreased in vivo glutamate/GABA ratio correlates with the social behavior deficit in a mouse model of autism spectrum disorder
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Gaeun Park, Se Jin Jeon, In Ok Ko, Ji Hwan Park, Kyo Chul Lee, Min-Sik Kim, Chan Young Shin, Hyeonjin Kim, Yong-Seok Lee
2022 Volume 15, Issue 1, p19
Abstract
<jats:title>Abstract</jats:title>To diagnose autism spectrum disorder (ASD), researchers have sought biomarkers whose alterations correlate with the susceptibility to ASD. However, biomarkers closely related to the pathophysiology of ASD are lacking. Even though excitation/inhibition (E/I) imbalance has been suggested as an underlying mechanism of ASD, few studies have investigated the actual ratio of glutamate (Glu) to γ-aminobutyric acid (GABA) concentration in vivo. Moreover, there are controversies in the directions of E/I ratio alterations even in extensively studied ASD animal models. Here, using proton magnetic resonance spectroscopy (<jats:sup>1</jats:sup>H-MRS) at 9.4T, we found significant differences in the levels of different metabolites or their ratios in the prefrontal cortex and hippocampus of <jats:italic>Cntnap2</jats:italic><jats:sup>−/−</jats:sup> mice compared to their wild-type littermates. The Glu/GABA ratio, N-acetylaspartate (NAA)/total creatine (tCr) ratio, and tCr level in the prefrontal cortex were significantly different in <jats:italic>Cntnap2</jats:italic><jats:sup>−/−</jats:sup> mice compared to those in wild-type mice, and they significantly correlated with the sociability of mice. Moreover, receiver operating characteristic (ROC) analyses indicated high specificity and selectivity of these metabolites in discriminating genotypes. These results suggest that the lowered Glu/GABA ratio in the prefrontal cortex along with the changes in the other metabolites might contribute to the social behavior deficit in <jats:italic>Cntnap2</jats:italic><jats:sup>−/−</jats:sup> mice. Our results also demonstrate the utility of <jats:sup>1</jats:sup>H-MRS in investigating the underlying mechanisms or the diagnosis of ASD.
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