PUBLICATION
Midazolam Exposure Impedes Oligodendrocyte Development via the Translocator Protein and Impairs Myelination in Larval Zebrafish
- Authors
- Xu, D., Wang, B., Xu, B., Yin, C., Ning, L., Li, X., Du, J., Wang, Y.
- ID
- ZDB-PUB-211010-4
- Date
- 2021
- Source
- Molecular neurobiology 59(1): 93-106 (Journal)
- Registered Authors
- Du, Jiu Lin
- Keywords
- Midazolam, Myelination, Oligodendrocyte, Translocator protein, Zebrafish
- MeSH Terms
-
- Anesthetics, Intravenous/pharmacology*
- Animals
- Cell Differentiation/drug effects*
- Cell Differentiation/physiology
- Midazolam/pharmacology*
- Myelin Sheath/metabolism*
- Oligodendrocyte Precursor Cells/drug effects*
- Oligodendrocyte Precursor Cells/metabolism
- Oligodendroglia/drug effects
- Oligodendroglia/metabolism
- Receptors, GABA/genetics
- Receptors, GABA/metabolism*
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 34626343 Full text @ Mol. Neurobiol.
Citation
Xu, D., Wang, B., Xu, B., Yin, C., Ning, L., Li, X., Du, J., Wang, Y. (2021) Midazolam Exposure Impedes Oligodendrocyte Development via the Translocator Protein and Impairs Myelination in Larval Zebrafish. Molecular neurobiology. 59(1):93-106.
Abstract
Anesthetics are commonly used in various medical procedures. Accumulating evidence suggests that early-life anesthetics exposure in infants and children affects brain development, causing psychiatric and neurological disorders. However, the underlying mechanisms are poorly understood. Using zebrafish larvae as a model, we found that the proliferation and migration of oligodendrocyte progenitor cells (OPCs) were severely impaired by the exposure of midazolam (MDZ), an anesthetic widely used in pediatric surgery and intensive care medicine, leading to a reduction of oligodendroglial lineage cell in the dorsal spinal cord. This defect was mimicked by the bath application of translocator protein (TSPO) agonists and partially rescued by genetic downregulation of TSPO. Cell transplantation experiments showed that requirement of TSPO for MDZ-induced oligodendroglial lineage cell defects is cell-autonomous. Furthermore, transmission electron microscopy and in vivo electrophysiological recording experiments demonstrated that MDZ exposure caused axon hypomyelination and action potential propagation retardation, resulting in delayed behavior initiation. Thus, our findings reveal that MDZ affects oligodendroglial lineage cell development and myelination in young animals, raising the care about its clinic use in infants and children.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping