S-ketamine exposure in early postnatal period induces social deficit mediated by excessive microglial synaptic pruning
Hongyu Zhong, Rou Xue, Ya-Ning Han, Lei Liu, Jian-Shuai Zhao, Min Cai, Sa Wang, Peng-Fei Wei, Guang-Chao Zhao, Hai-Long Dong
Molecular Psychiatry March 11, 2025 DOI: 10.1038/s41380-025-02949-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Early postnatal animals (species not stated in the abstract) |
| Interventions | S-ketamine nor-NOHA |
| Measures | Social Behavioral Atlas (SBeA) |
| Topics | Esketamine Ketamine |
| Key points | Early postnatal S-ketamine exposure specifically induced deficits in sociability and social cognition in adolescence, accompanied by persistent microglial activation in the prefrontal cortex, excessive synaptic pruning, dendritic abnormalities, and excitatory synaptic overexcitation. The authors report that downregulating Arg1 or prophylactic administration of the Arg1 inhibitor nor-NOHA reversed microglial overactivation and attenuated the neurodevelopmental disturbance. |
Abstract
The impact of general anesthetics on neurodevelopment is highly controversial in terms of clinical and preclinical studies. Evidence mounted in recent years indicated development of social cognitions was more susceptible to general anesthesia in early life. However, the behavioral characterization during adolescence and underlying mechanisms remains unclear. Herein, we observed that early postnatal S-ketamine exposure specifically induced deficits in sociability and social cognition via a machine learning assistant behavioral analysis toolbox- Social Behavioral Atlas (SBeA). Furthermore, S-ketamine exposure constantly activates microglia in the prefrontal cortex (PFC), mediating excessive synaptic pruning and dendritic structural abnormalities, leading to overexcitation of excitatory synaptic transmission. Notably, S-ketamine exposure activated Stat1-Arg1 pathway in microglia. Downregulating Arg1 expression or prophylactic administrating Arg1 selective inhibitor nor-NOHA could reverse microglial overactivation and attenuate the neurodevelopmental disturbance induced by S-ketamine exposure. Our study identifies the abnormal behavioral phenotypes in adolescence induced by early postnatal S-ketamine exposure and reveals a potential target for preventing anesthesia-related neurodevelopmental abnormalities.
Comparable studies
Other preclinical and animal studies on esketamine, most cited first.
Citations in the library
Cites 4
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