Related Experiment Video
Updated: Jun 29, 2025
Primary Microglia Isolation from Mixed Glial Cell Cultures of Neonatal Rat Brain Tissue
Published on: August 15, 2012
Complement C1q-mediated microglial synaptic elimination by enhancing desialylation underlies sevoflurane-induced
Gang Wang1,2, Hua-Yue Liu1,2,3, Xiao-Wen Meng1,2
1Department of Anesthesiology, First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
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.
Insights
Repeated sevoflurane anesthesia in newborns causes cognitive deficits by triggering microglia to eliminate synapses via complement C1q. Inhibiting C1q or sialidase may prevent this neurotoxicity.
Area of Science:
- Neuroscience
- Anesthesiology
- Immunology
Background:
- Neonatal exposure to sevoflurane can lead to long-term neurocognitive impairments.
- Microglia and complement C1q are implicated in sevoflurane-induced neurotoxicity.
Purpose of the Study:
- To investigate the role of microglia and complement C1q in sevoflurane-induced neurotoxicity.
- To explore the mechanisms underlying sevoflurane's effects on synaptic function and cognition.
Main Methods:
- Neonatal mice received sevoflurane exposure, followed by cognitive assessments using the Morris water maze.
- Mechanisms were explored using minocycline, C1q antibody (ANX005), and a sialidase inhibitor (NADNA).
- Techniques included Western blotting, RT-qPCR, Golgi staining, 3D reconstruction, immunofluorescence, and in vitro BV2 cell assays.
Main Results:
- Sevoflurane exposure caused learning and cognitive deficits, microglial activation, and synapse loss in young mice.
- Sevoflurane enhanced microglia-mediated synapse elimination via C1q binding, involving neuronal sialic acid desialylation.
- Inhibition of C1q or sialidase activity significantly improved cognitive function and reduced synapse loss.
Conclusions:
- C1q-mediated microglial synaptic elimination, driven by desialylation, contributes to sevoflurane-induced developmental neurotoxicity.
- Targeting C1q or sialidase presents a potential therapeutic strategy against sevoflurane neurotoxicity.
