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Open Access Research

Neurodevelopmental alcohol exposure elicits long-term changes to gene expression that alter distinct molecular pathways dependent on timing of exposure

Morgan L Kleiber, Katarzyna Mantha, Randa L Stringer and Shiva M Singh*

Author Affiliations

Molecular Genetics Unit, Department of Biology, University of Western Ontario, London, Ontario, N6A 5B7, Canada

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Journal of Neurodevelopmental Disorders 2013, 5:6  doi:10.1186/1866-1955-5-6

Published: 13 March 2013

Abstract

Background

Maternal alcohol consumption is known to adversely affect fetal neurodevelopment. While it is known that alcohol dose and timing play a role in the cognitive and behavioral changes associated with prenatal alcohol exposure, it is unclear what developmental processes are disrupted that may lead to these phenotypes.

Methods

Mice (n=6 per treatment per developmental time) were exposed to two acute doses of alcohol (5 g/kg) at neurodevelopmental times representing the human first, second, or third trimester equivalent. Mice were reared to adulthood and changes to their adult brain transcriptome were assessed using expression arrays. These were then categorized based on Gene Ontology annotations, canonical pathway associations, and relationships to interacting molecules.

Results

The results suggest that ethanol disrupts biological processes that are actively occurring at the time of exposure. These include cell proliferation during trimester one, cell migration and differentiation during trimester two, and cellular communication and neurotransmission during trimester three. Further, although ethanol altered a distinct set of genes depending on developmental timing, many of these show interrelatedness and can be associated with one another via ‘hub’ molecules and pathways such as those related to huntingtin and brain-derived neurotrophic factor.

Conclusions

These changes to brain gene expression represent a ‘molecular footprint’ of neurodevelopmental alcohol exposure that is long-lasting and correlates with active processes disrupted at the time of exposure. This study provides further support that there is no neurodevelopmental time when alcohol cannot adversely affect the developing brain.

Keywords:
Fetal alcohol spectrum disorders; Development; Brain; Mouse; Gene expression; Expression array