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Diazepam-induced neural tube closure defects in explanted early chick embryos
Abstract:
The effects of diazepam on the development of explanted stage 4 chick embryos were investigated. Diazepam, at 10-120 micrograms/ml, preferentially inhibited closure of the neural tube. This effect was reversible. Concentrations of 150-200 micrograms/ml inhibited not only neural tube closure but also blastodermal expansion, somite formation, and heart development in 52% of the embryos. Concentrations above 200 micrograms/ml were highly embryotoxic. Electron microscopy of affected neuroepithelial cells revealed that 1) apical surfaces were much smoother than usual and 2) apical filament bundles, which are generally thought to provide motive forces for uplifting of neural folds, were not well organized and often lacked alternating dark and light areas along their length. These findings and the fact that changes in cell surface topography reflect the contractile activities of underlying filament bundles suggest that the observed "smoothing" effect on apical cell surfaces and neural tube closure defects are due, at least in part, to the impaired ability of these filament bundles to contract.
Insights
Diazepam disrupts chick embryo development by inhibiting neural tube closure. This drug interferes with crucial cellular structures, impacting embryonic growth and potentially causing birth defects.
Area of Science:
- Developmental Biology
- Teratology
- Neuroscience
Background:
- Diazepam is a commonly prescribed anxiolytic medication.
- Understanding drug effects on embryonic development is crucial for public health.
- Chick embryos provide a valuable model for studying early vertebrate development.
Purpose of the Study:
- To investigate the effects of diazepam on the development of explanted stage 4 chick embryos.
- To identify specific developmental processes affected by diazepam exposure.
- To elucidate the cellular mechanisms underlying diazepam-induced developmental abnormalities.
Main Methods:
- Explantation of stage 4 chick embryos.
- Exposure to varying concentrations of diazepam (10-200 µg/ml).
- Light and electron microscopy of neuroepithelial cells.
Main Results:
- Diazepam inhibited neural tube closure in a dose-dependent manner.
- Higher concentrations also affected blastodermal expansion, somite formation, and heart development.
- Electron microscopy revealed disorganized apical filament bundles in neuroepithelial cells, suggesting impaired contractility.
Conclusions:
- Diazepam interferes with key embryonic developmental processes in chick embryos.
- Disruption of apical filament bundle organization and function likely contributes to neural tube closure defects.
- These findings highlight the potential teratogenic risks associated with diazepam exposure during early development.