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Published on: November 19, 2013
Esketamine Exposure Affects Neurodevelopment and Glutamate-NMDAR Signaling in Zebrafish Larvae
Jingyi Wang1, Shuo Huang2,3, Tingting Lin1
1Department of Neurosurgery, Xiang'an Hospital of Xiamen University, State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, Xiamen, China.
Insights
Esketamine, an N-methyl-D-aspartate receptor antagonist, affects zebrafish neurodevelopment, causing hyperactivity and altered gene expression. Glutamatergic signaling may be involved, highlighting potential pediatric risks.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Esketamine is used perioperatively in children due to its rapid action.
- Concerns exist regarding esketamine's potential neurotoxicity during early development.
- Zebrafish larvae offer a model to study neurodevelopmental effects.
Purpose of the Study:
- To investigate the impact of esketamine on neurodevelopment and function in zebrafish larvae.
- To explore the role of glutamatergic signaling in esketamine's effects.
- To provide insights for the safe clinical application of esketamine in pediatric populations.
Main Methods:
- Zebrafish larvae were exposed to esketamine (10 mg/L and 100 mg/L) for 2 and 6 hours.
- Behavioral assays (locomotion, dark preference) were performed.
- Glutamate levels and gene expression (NMDAR, neurodevelopment) were analyzed.
Main Results:
- Esketamine exposure led to hyperlocomotion and increased dark preference in larvae.
- Glutamate levels were elevated post-exposure.
- Significant alterations in NMDAR and neurodevelopment-related gene expression were observed.
- N-methyl-D-aspartate (NMDA) reversed esketamine-induced hyperactivity.
Conclusions:
- Esketamine significantly impacts neurodevelopment and function in zebrafish larvae.
- Glutamatergic signaling is a potential key mechanism underlying these effects.
- Findings suggest caution and further research for pediatric esketamine use.
Abstract:
Esketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has become a preferred option for perioperative use in infants and young children with low compliance due to its rapid onset and convenient administration. However, concerns regarding its potential neurotoxic effects during development warrant further investigation. This study aimed to elucidate the impact of esketamine on neurodevelopment and function in zebrafish larvae. Five days post-fertilization (dpf) zebrafish larvae were exposed to esketamine at concentrations of 10 mg/L and 100 mg/L for 2 and 6 h. The results demonstrated that esketamine exposure induced hyperlocomotion and increased dark preference in the larvae. Additionally, it elevated glutamate levels and significantly altered the expression of genes related to NMDAR and neurodevelopment. N-methyl-D-aspartate (NMDA) is an agonist of the NMDAR that reverses esketamine-induced hyperactivity and manf overexpression. In conclusion, esketamine exerts discernible effects on neurodevelopment and function in zebrafish larvae, with glutamatergic signaling potentially serving as a key underlying mechanism. These findings provide novel insights into the potential effects of clinical use of esketamine in pediatric populations, facilitating its safer application.
