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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Autistic-like social deficits in hippocampal MeCP2 knockdown rat models are rescued by ketamine

  • Choi, Miyeon (Hanyang Biomedical Research Institute, Hanyang University) ;
  • Ko, Seung Yeon (Hanyang Biomedical Research Institute, Hanyang University) ;
  • Seo, Jee Young (Graduate School of Biomedical Science and Engineering, Hanyang University) ;
  • Kim, Do Gyeong (Graduate School of Biomedical Science and Engineering, Hanyang University) ;
  • Lee, Huiju (Graduate School of Biomedical Science and Engineering, Hanyang University) ;
  • Chung, Heekyoung (Graduate School of Biomedical Science and Engineering, Hanyang University) ;
  • Son, Hyeon (Graduate School of Biomedical Science and Engineering, Hanyang University)
  • Received : 2022.02.24
  • Accepted : 2022.03.18
  • Published : 2022.05.31
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Abstract

Autism or autism spectrum disorder (ASD) is a behavioral syndrome characterized by persistent deficits in social interaction, and repetitive patterns of behavior, interests, or activities. The gene encoding Methyl-CpG binding protein 2 (MeCP2) is one of a few exceptional genes of established causal effect in ASD. Although genetically engineered mice studies may shed light on how MeCP2 loss affects synaptic activity patterns across the whole brain, such studies are not considered practical in ASD patients due to the overall level of impairment, and are technically challenging in mice. For the first time, we show that hippocampal MeCP2 knockdown produces behavioral abnormalities associated with autism-like traits in rats, providing a new strategy to investigate the efficacy of therapeutics in ASD. Ketamine, an N-Methyl-D-aspartate (NMDA) blocker, has been proposed as a possible treatment for autism. Using the MeCP2 knockdown rats in conjunction with a rat model of valproic acid (VPA)-induced ASD, we examined gene expression and ASD behaviors upon ketamine treatment. We report that the core symptoms of autism in MeCP2 knockdown rats with social impairment recovered dramatically following a single treatment with ketamine.

Keywords

Acknowledgement

This work was supported by a National Research Foundation of Korea (NRF) Grant (No.2019R1A2C2003616 to H.S.), and a Medical Research Center Grant (No. 2017R1A5A2015395 to H.S.); it was also supported by Basic Science Research Program NRF Grants (No. 2017R1D1AB03032858 and No. 2020 R1I1A1A01060863 to M.C., and No. 2021R1I1A1A01054879 to S.Y.K.) funded by the Ministry of Science and Technology, Republic of Korea; and an Institute of Information & Communications Technology Planning & Evaluation (IITP) grant funded by the Korea Government (MSIT) (No.2020-0-01373, Artificial Intelligence Graduate School Program (Hanyang University)) and the research fund of Hanyang University (HY-202000000700013).

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