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].
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 3
- Effect of Ketamine Treatment on Social Withdrawal in Autism and Autism-Like Conditions. Clinical Neuropharmacology
- MeCP2 prevents against sustained ketamine-induced synaptic depression at inhibitory synapses. iScience June 20, 2025
- Therapeutic potential of classic and non-classic psychedelics in neurodevelopmental disorders: Opportunities and challenges Pharmacological Research August 26, 2026
Cites 2
- N-Methyl-D-Aspartate Receptors, Ketamine, and Rett Syndrome: Something Special on the Road to Treatments? Biological Psychiatry May 1, 2016
- Brain activity mapping in Mecp2 mutant mice reveals functional deficits in forebrain circuits, including key nodes in the default mode network, that are reversed with ketamine treatment. Journal of Neuroscience October 3, 2012