TREM2 Expression on Mouse Astrocytes Prevents Sevoflurane-Induced Developmental Neurotoxicity Through Microglial Pruning of Dendritic Spines in Hippocampal CA1 Region

Research Background and Significance

Sevoflurane is one of the most widely used anesthetics in pediatric anesthesia. Early multiple exposures to sevoflurane can lead to developmental neurotoxicity in mice, but its underlying mechanism remains unclear. Triggering receptor expressed on myeloid cells 2 (TREM2) is crucial for microglia-mediated synaptic refinement during early brain development. This study explores the impact of TREM2 on dendritic spine pruning in the mouse hippocampal CA1 region during sevoflurane-induced developmental neurotoxicity.

Research Source

This study was conducted by Deng Li, Song Shaoyong, Zhao Weiming, Meng Xiaowen, Liu Hong, Zheng Qing, Peng Ke, and Ji Fuhai, affiliated with the Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences. The research findings were published in the journal “Neuroscience Bulletin” in 2024.

Detailed Research Process

a) Research Design and Methods

1. Experimental Model Construction: Mice were anesthetized with sevoflurane on postnatal days 6, 8, and 10, followed by open field tests and Morris water maze tests to assess behavioral performance;
2. Genetic Manipulation: Stereotaxic injection was used for TREM2 knockdown and overexpression experiments;
3. Biochemical Analysis: Western blot, immunofluorescence, electron microscopy, 3D reconstruction, Golgi staining, and whole-cell patch-clamp recording experiments were conducted.

b) Main Research Results

• Sevoflurane exposure upregulated TREM2 protein expression in the mouse hippocampus and increased microglia-mediated dendritic spine pruning;
• TREM2 knockdown significantly reduced dendritic spine pruning and partially exacerbated neuromorphological abnormalities and cognitive deficits in sevoflurane-treated mice;
• Conversely, TREM2 overexpression enhanced microglia-mediated dendritic spine pruning, repaired neuromorphological abnormalities, and alleviated cognitive dysfunction.

c) Research Conclusions and Value

TREM2 plays a protective role against neurocognitive damage following neonatal sevoflurane exposure in mice by enhancing microglia-mediated dendritic spine pruning in CA1 neurons, providing a potential therapeutic target for preventing sevoflurane-induced developmental neurotoxicity.

d) Research Highlights

• This study breakthrough reveals the role of TREM2 in microglia-mediated synaptic pruning, suggesting a possible pathway for preventing developmental neurotoxicity;
• It provides scientific evidence for safety assessment of anesthetic use during development, with important clinical application value.

Research Significance and Prospects

This study fills the gap in understanding the role of TREM2 in the mechanism of neurological damage caused by early anesthetic exposure. Future research needs to further explore the specific molecular mechanisms by which sevoflurane affects TREM2 expression, aiming to provide scientific basis for best practices in pediatric anesthesia.