Decreased in vivo glutamate/GABA ratio correlates with the social behavior deficit in a mouse model of autism spectrum disorder

Molecular Brain

Gaeun Park¹  Yong-Seok Lee²  Hyeonjin Kim³  Ji Hwan Park⁴  Min-Sik Kim⁴  In Ok Ko⁵  Kyo Chul Lee⁵  Chan Young Shin⁶  Se Jin Jeon⁶ 

[1] Department of Biomedical Sciences, BK21 Four Biomedical Science Program, Seoul National University College of Medicine, Seoul, Republic of Korea;Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea;Department of Biomedical Sciences, BK21 Four Biomedical Science Program, Seoul National University College of Medicine, Seoul, Republic of Korea;Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea;Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea;Wide River Institute of Immunology, Seoul National University, Hongcheon, Republic of Korea;Department of Medical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea;Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea;Division of Applied RI, Korea Institute Radiological and Medical Sciences, Seoul, Republic of Korea;School of Medicine and Center for Neuroscience Research, Konkuk University, Seoul, Republic of Korea;

关键词: Autism spectrum disorder;    E/I balance;    Glu/GABA;    Creatine;    Sociability;    Magnetic resonance spectroscopy;   

DOI  :  10.1186/s13041-022-00904-z

来源: Springer

【 摘 要 】

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 (1H-MRS) at 9.4T, we found significant differences in the levels of different metabolites or their ratios in the prefrontal cortex and hippocampus of Cntnap2−/− 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 Cntnap2−/− 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 Cntnap2−/− mice. Our results also demonstrate the utility of 1H-MRS in investigating the underlying mechanisms or the diagnosis of ASD.

【 授权许可】

CC BY