2. Academic Validation
  3. Microglia-mediated Perineuronal nets loss contributes to social memory deficit in male mice after repeated neonatal sevoflurane exposure

Microglia-mediated Perineuronal nets loss contributes to social memory deficit in male mice after repeated neonatal sevoflurane exposure

  • Brain Behav Immun. 2025 Oct 23:131:106148. doi: 10.1016/j.bbi.2025.106148.
Ziwen Shi 1,  Jingwen Qin 1,  Lin Gao 2,  Fa Huang 1,  Wei Wei 1,  Tianyun Zhao 1,  Xingrong Song 3,  Xinying Guo 4
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, China.
  • 2 Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, China; Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
  • 3 Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, China; Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, China. Electronic address: sxjess@126.com.
  • 4 Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, China. Electronic address: sarah_guoxy@163.com.
PMID: 41138885 DOI: 10.1016/j.bbi.2025.106148
Abstract

Background: Repeated early-life exposure to general anesthetics might affect social behavior. Perineuronal nets (PNNs), which enwrap around parvalbumin (PV) interneurons and support their function, are crucial for social memory. Given that microglia contribute to PNN remodeling and are responsive to anesthetic exposure, we hypothesized that repeated neonatal sevoflurane exposure impairs social memory via microglia-mediated PNN degradation.

Methods: Mice were exposed to 2.5 % sevoflurane for 2 h daily during postnatal days 7-9. At postnatal day 28, we evaluated social behavior, PNN integrity, patch-clamp recordings, and conducted analyses of microglia and PV interneurons. Subsequently, we explored the effects of microglia depletion by PLX5622 (CSF1R antagonist) and repopulation on social behavior and PNNs after repeated sevoflurane exposure.

Results: We found that repeated neonatal sevoflurane exposure led to social memory deficit in male mice. This deficit coincided with significant PNN loss in the prefrontal cortex, increased excitability of PV interneurons, and enhanced inhibitory input to pyramidal neurons. Microglia exhibited elevated phagocytic activity toward PNNs after repeated neonatal sevoflurane exposure. Notably, microglial depletion and repopulation rescued PNN integrity and social memory performance.

Conclusions: Our findings reveal microglia-dependent PNN degradation as a key mechanism underlying early-life sevoflurane exposure-induced social memory impairments in male mice. Targeting microglial activity or preserving PNNs may offer new strategies to prevent anesthesia-induced neurodevelopmental impairments.

Keywords

Microglia; Neonatal; Parvalbumin; Perineuronal nets; Sevoflurane.

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