Decreased in vivo glutamate/GABA ratio correlates with the social behavior deficit in a mouse model of autism spectrum disorder
Abstract 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 a...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-02-01
|
| Series: | Molecular Brain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13041-022-00904-z |
| _version_ | 1819277722083393536 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Gaeun Park |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-24T00:00:37Z |
| format | Article |
| id | doaj.art-92f509b5c41443ed950d6ca2d9bbe961 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-24T00:00:37Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-92f509b5c41443ed950d6ca2d9bbe9612022-12-21T17:25:09ZengBMCMolecular Brain1756-66062022-02-0115111210.1186/s13041-022-00904-zDecreased in vivo glutamate/GABA ratio correlates with the social behavior deficit in a mouse model of autism spectrum disorderGaeun Park0Se Jin Jeon1In Ok Ko2Ji Hwan Park3Kyo Chul Lee4Min-Sik Kim5Chan Young Shin6Hyeonjin Kim7Yong-Seok Lee8Department of Biomedical Sciences, BK21 Four Biomedical Science Program, Seoul National University College of MedicineSchool of Medicine and Center for Neuroscience Research, Konkuk UniversityDivision of Applied RI, Korea Institute Radiological and Medical SciencesDepartment of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST)Division of Applied RI, Korea Institute Radiological and Medical SciencesDepartment of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST)School of Medicine and Center for Neuroscience Research, Konkuk UniversityDepartment of Medical Sciences, Seoul National University College of MedicineDepartment of Biomedical Sciences, BK21 Four Biomedical Science Program, Seoul National University College of MedicineAbstract 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.https://doi.org/10.1186/s13041-022-00904-zAutism spectrum disorderE/I balanceGlu/GABACreatineSociabilityMagnetic resonance spectroscopy |
| spellingShingle | 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 Decreased in vivo glutamate/GABA ratio correlates with the social behavior deficit in a mouse model of autism spectrum disorder Molecular Brain Autism spectrum disorder E/I balance Glu/GABA Creatine Sociability Magnetic resonance spectroscopy |
| title | Decreased in vivo glutamate/GABA ratio correlates with the social behavior deficit in a mouse model of autism spectrum disorder |
| title_full | Decreased in vivo glutamate/GABA ratio correlates with the social behavior deficit in a mouse model of autism spectrum disorder |
| title_fullStr | Decreased in vivo glutamate/GABA ratio correlates with the social behavior deficit in a mouse model of autism spectrum disorder |
| title_full_unstemmed | Decreased in vivo glutamate/GABA ratio correlates with the social behavior deficit in a mouse model of autism spectrum disorder |
| title_short | Decreased in vivo glutamate/GABA ratio correlates with the social behavior deficit in a mouse model of autism spectrum disorder |
| title_sort | decreased in vivo glutamate gaba ratio correlates with the social behavior deficit in a mouse model of autism spectrum disorder |
| topic | Autism spectrum disorder E/I balance Glu/GABA Creatine Sociability Magnetic resonance spectroscopy |
| url | https://doi.org/10.1186/s13041-022-00904-z |
| work_keys_str_mv | AT gaeunpark decreasedinvivoglutamategabaratiocorrelateswiththesocialbehaviordeficitinamousemodelofautismspectrumdisorder AT sejinjeon decreasedinvivoglutamategabaratiocorrelateswiththesocialbehaviordeficitinamousemodelofautismspectrumdisorder AT inokko decreasedinvivoglutamategabaratiocorrelateswiththesocialbehaviordeficitinamousemodelofautismspectrumdisorder AT jihwanpark decreasedinvivoglutamategabaratiocorrelateswiththesocialbehaviordeficitinamousemodelofautismspectrumdisorder AT kyochullee decreasedinvivoglutamategabaratiocorrelateswiththesocialbehaviordeficitinamousemodelofautismspectrumdisorder AT minsikkim decreasedinvivoglutamategabaratiocorrelateswiththesocialbehaviordeficitinamousemodelofautismspectrumdisorder AT chanyoungshin decreasedinvivoglutamategabaratiocorrelateswiththesocialbehaviordeficitinamousemodelofautismspectrumdisorder AT hyeonjinkim decreasedinvivoglutamategabaratiocorrelateswiththesocialbehaviordeficitinamousemodelofautismspectrumdisorder AT yongseoklee decreasedinvivoglutamategabaratiocorrelateswiththesocialbehaviordeficitinamousemodelofautismspectrumdisorder |