Toxic effects of midazolam on differentiating neurons in vitro as a consequence of suppressed neuronal Ca 2+-oscillations
Sinner B, Friedrich O, Zausig Y, Bein T, Graf B (2011)
Publication Language: English
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2011
Journal
Publisher: Elsevier
Book Volume: 290
Pages Range: 96-101
Journal Issue: 1
URI: http://www.sciencedirect.com/science/article/pii/S0300483X1100326X
DOI: 10.1016/j.tox.2011.08.022
Abstract
Background: In immature neurons anesthetics induce apoptosis and influence neuronal differentiation. Neuronal Ca -oscillations regulate differentiation and synaptogenesis. We examined the effects of the long-term blockade of hippocampal Ca -oscillations with midazolam on neuronal synapsin expression. Material and methods: Hippocampal neurons were incubated at day 15 in culture with the specific GABA receptor agonist muscimol (50μM) or with midazolam (100 and 300nM), respectively, for 24h. TUNEL and activated-Caspase-3 staining were used to detect apoptotic neurons. Ca -oscillations were detected using the Ca -sensitive dye FURA-2 and dual wavelength excitation fluorescence microscopy. Synapsin was identified with confocal anti-synapsin immunofluorescence microscopy. Results: Muscimol, when applied for 24h, decreased the amplitude and frequency Ca -oscillations significantly. Midazolam concentration-dependently suppressed the amplitude and frequency of the Ca -oscillations. This was associated by a downregulation of the synapsin expression 24h after washout. Conclusion: Neuronal Ca -oscillations mediate neuronal differentiation and are involved in synaptogenesis. By acting via the GABA receptor, midazolam exerts its toxic effect through the suppression of neuronal Ca -oscillations, a reduction in synapsin expression and consecutively reduced synaptic integrity. © 2011 Elsevier Ireland Ltd.
Authors with CRIS profile
Involved external institutions
Germany (DE)How to cite
APA:
Sinner, B., Friedrich, O., Zausig, Y., Bein, T., & Graf, B. (2011). Toxic effects of midazolam on differentiating neurons in vitro as a consequence of suppressed neuronal Ca 2+-oscillations. Toxicology, 290(1), 96-101. https://dx.doi.org/10.1016/j.tox.2011.08.022
MLA:
Sinner, Barbara, et al. "Toxic effects of midazolam on differentiating neurons in vitro as a consequence of suppressed neuronal Ca 2+-oscillations." Toxicology 290.1 (2011): 96-101.
BibTeX: Download