Autistic-like social deficits in hippocampal MeCP2 knockdown rat models are rescued by ketamine.
Miyeon Choi, Seung Yeon Ko, Jee Young Seo, Do Gyeong Kim, Huiju Lee, Heekyoung Chung, Hyeon Son
BMB reports May 2022 DOI: 10.5483/bmbrep.2022.55.5.038 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats with hippocampal MeCP2 knockdown and rats with valproic acid-induced autism-like traits |
| Intervention | Ketamine |
| Duration | Single treatment |
| Topics | Esketamine Ketamine |
| Key findings | The authors report that core autism symptoms, including social impairment, recovered dramatically in MeCP2 knockdown rats after a single ketamine treatment. They propose hippocampal MeCP2 knockdown in rats as a new strategy for investigating autism therapeutics, tested alongside a valproic acid-induced autism model. |
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. [BMB Reports 2022; 55(5): 238-243].