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Updated: Apr 21, 2026
Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
Published on: May 12, 2015
Single sevoflurane exposure increases methyl-CpG island binding protein 2 phosphorylation in the hippocampus of
Xiao-Dan Han1, Min Li1, Xiao-Guang Zhang1
1Department of Anesthesia, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Abstract:
Sevoflurane is an inhaled anesthetic that is widely used in clinical practice, particularly for pediatric anesthesia. Previous studies have suggested that sevoflurane may induce neurotoxicity in the brains of neonatal mice. In the present study, the possible mechanism of neurodegeneration induced by sevoflurane in the developing brain, and the possibility that memantine treatment is able to reverse this phenomenon, were investigated. On postnatal day 7 (P7) C57BL/6 mice were continuously exposed to 1.5% sevoflurane for 2 h following pre-injection of saline or memantine. Methyl-CpG island binding protein 2 (MeCP2), cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) expression in the hippocampus was measured by western blotting. Exposure to 1.5% sevoflurane resulted in increased MeCP2 phosphorylation in the hippocampus, which was reversed by memantine injection. However, neither CREB phosphorylation nor BDNF expression were significantly altered by sevoflurane treatment. The current study indicated that sevoflurane causes neurotoxicity in the developing brain, and that this may be attributed to increased MeCP2 phosphorylation in the hippocampus. It was also demonstrated that this neurotoxicity can be prevented by the N-methyl-D-aspartate glutamate receptor inhibitor memantine.
Insights
Sevoflurane anesthesia may harm developing brains by increasing MeCP2 phosphorylation. Memantine, an N-methyl-D-aspartate receptor inhibitor, prevented this neurotoxic effect in neonatal mice.
Area of Science:
- Neuroscience
- Anesthesiology
- Developmental Biology
Background:
- Sevoflurane is a common inhaled anesthetic, especially in pediatric anesthesia.
- Previous research suggests sevoflurane may cause neurotoxicity in neonatal brains.
- The precise mechanism and potential interventions for sevoflurane-induced neurotoxicity remain under investigation.
Purpose of the Study:
- To investigate the mechanism of sevoflurane-induced neurodegeneration in the developing brain.
- To determine if memantine can reverse sevoflurane-induced neurotoxicity.
- To explore the role of MeCP2, CREB, and BDNF in sevoflurane neurotoxicity.
Main Methods:
- Neonatal C57BL/6 mice were exposed to sevoflurane with or without memantine pre-injection.
- Hippocampal expression of MeCP2, CREB, and BDNF was analyzed using western blotting.
- MeCP2 phosphorylation was specifically assessed as a marker of cellular stress.
Main Results:
- Sevoflurane exposure led to increased MeCP2 phosphorylation in the hippocampus.
- Memantine treatment reversed the observed increase in MeCP2 phosphorylation.
- CREB phosphorylation and BDNF expression were not significantly altered by sevoflurane.
Conclusions:
- Sevoflurane induces neurotoxicity in the developing brain, potentially via increased MeCP2 phosphorylation.
- Memantine, an N-methyl-D-aspartate receptor antagonist, can prevent sevoflurane-induced neurotoxicity.
- These findings suggest a potential therapeutic strategy for mitigating anesthetic-induced neurodevelopmental risks.
