Differential Effects of Sevoflurane Exposure on Long-Term Fear Memory in Neonatal and Adult Rats

Li, Changsheng; Liu, Sufang; Mei, Yixin; Wang, Qingyong; Lu, Xihua; Li, Hongle; Tao, Feng

doi:10.1007/s12035-021-02629-x

Cited by 3 publications

(1 citation statement)

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“…Sevoflurane-induced neurotoxicity is closely related to the hippocampus, a brain area that plays a critical role in cognition [ 11 ]. Sevoflurane-treated mice exhibited neurocognitive impairment, alterations in hippocampal synaptic transmission, synapse loss, and dendritic damage [ 12 – 14 ]. However, the mechanism of sevoflurane-induced neurotoxicity is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Complement C1q-mediated microglial synaptic elimination by enhancing desialylation underlies sevoflurane-induced developmental neurotoxicity

Wang,

Liu,

Meng

et al. 2024

Cell Biosci

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Background Repeated neonatal sevoflurane exposures led to neurocognitive disorders in young mice. We aimed to assess the role of microglia and complement C1q in sevoflurane-induced neurotoxicity and explore the underlying mechanisms. Methods Neonatal mice were treated with sevoflurane on postnatal days 6, 8, and 10, and the Morris water maze was performed to assess cognitive functions. For mechanistic explorations, mice were treated with minocycline, C1q-antibody ANX005, and sialidase-inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (NADNA) before sevoflurane exposures. Western blotting, RT-qPCR, Golgi staining, 3D reconstruction and engulfment analysis, immunofluorescence, and microglial morphology analysis were performed. In vitro experiments were conducted in microglial cell line BV2 cells. Results Repeated neonatal sevoflurane exposures resulted in deficiencies in learning and cognition of young mice, accompanied by microglial activation and synapse loss. Sevoflurane enhanced microglia-mediated synapse elimination through C1q binding to synapses. Inhibition of microglial activation and phagocytosis with minocycline significantly reduced the loss of synapses. We further revealed the involvement of neuronal sialic acids in this process. The enhanced activity of sialidase by sevoflurane led to the loss of sialic acids, which facilitated C1q binding to synapses. Inhibition of C1q with ANX005 or inhibition of sialidase with NADNA significantly rescued microglia-mediated synapse loss and improved neurocognitive function. Sevoflurane enhanced the engulfment of BV2 cells, which was reversed by ANX005. Conclusions Our findings demonstrated that C1q-mediated microglial synaptic elimination by enhancing desialylation contributed to sevoflurane-induced developmental neurotoxicity. Inhibition of C1q or sialidase may be a potential therapeutic strategy for this neurotoxicity.

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Section: Introductionmentioning

confidence: 99%