Perturbations in cortical development and neuronal network excitability arising from prenatal exposure to benzodiazepines in mice

Haas, Matilda, Qu, Zhengdong, Kim, Tae Hwan, Vargas, Ernesto, Campbell, Kenneth, Petrou, Steven, Tan, Seong-Seng, Reid, Christopher A. and Heng, Julian (2013) Perturbations in cortical development and neuronal network excitability arising from prenatal exposure to benzodiazepines in mice. European Journal of Neuroscience, 37 10: 1584-1593. doi:10.1111/ejn.12167


Author Haas, Matilda
Qu, Zhengdong
Kim, Tae Hwan
Vargas, Ernesto
Campbell, Kenneth
Petrou, Steven
Tan, Seong-Seng
Reid, Christopher A.
Heng, Julian
Title Perturbations in cortical development and neuronal network excitability arising from prenatal exposure to benzodiazepines in mice
Journal name European Journal of Neuroscience   Check publisher's open access policy
ISSN 0953-816X
1460-9568
Publication date 2013
Sub-type Article (original research)
DOI 10.1111/ejn.12167
Open Access Status
Volume 37
Issue 10
Start page 1584
End page 1593
Total pages 10
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Subject 2800 Neuroscience
Abstract During brain development, many factors influence the assembly and final positioning of cortical neurons, and this process is essential for proper circuit formation and normal brain function. Among many important extrinsic factors that guide the maturation of embryonic cortical neurons, the secreted neurotransmitter GABA has been proposed to influence both their migratory behaviour and their terminal differentiation. The full extent of the short-term and long-term changes in brain patterning and function caused by modulators of the GABA system is not known. In this study, we specifically investigated whether diazepam, a commonly used benzodiazepine that modulates the GABAA receptor, alters neuronal positioning in vivo, and whether this can lead to lasting effects on brain function. We found that fetal exposure to diazepam did not change cell positioning within the embryonic day (E)14.5 mouse cerebral cortex, but significantly altered neuron positioning within the E18.5 cortex. In adult mice, diazepam treatment affected the distribution of cortical interneurons that express parvalbumin or calretinin, and also led to a decrease in the numbers of calretinin-expressing interneurons. In addition, we observed that neonatal exposure to diazepam altered the sensitivity of mice to a proconvulsant challenge. Therefore, exposure of the fetal brain to benzodiazepines has consequences for the positioning of neurons and cortical network excitability.
Keyword Cortical excitability
Cortical neurons
Neuronal migration
Seizure
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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Created: Mon, 27 Oct 2014, 17:06:47 EST by Sylvie Pichelin on behalf of Queensland Brain Institute