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Early-Ethanol Exposure Induced Region-Specific Changes in Metabolic Proteins in the Rat Brain: A Proteomics Study

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Abstract

In utero exposure to alcohol has been shown to cause a spectrum of cognitive and behavioral deficits. This study aimed to explore the long-term effects of early-ethanol exposure on proteins in the brain. Male Sprague-Dawley rat pups were exposed to 12% ethanol (4 g/kg/day i.p.) or volume-controlled saline during the third human trimester equivalent (P4–P9). At P31, prefrontal cortex (PFC) and dorsal hippocampus (DH) proteins were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography mass spectrometry (LC-MS). Early-ethanol exposure increased the capacity for metabolism of NADH and oxidative phosphorylation, as shown by an upregulation of NADH dehydrogenase (ubiquinone, 1 alpha subcomplex 9) while simultaneously decreasing the capacity to protect against oxidative stress in the PFC. Early-ethanol exposure decreased the capacity for ATP synthesis (> 2-fold down regulation of ATP synthase) and increased glycogen synthesis in the DH (> 2-fold decrease in glycogen synthase kinase-3β). The effects of early-ethanol exposure on glucose metabolism and ATP production appeared to be region specific. In addition, early-ethanol exposure decreased structural proteins in both the PFC and DH. A greater number of proteins were altered in the DH than in the PFC, indicating that the DH may be more susceptible to the effects of early-ethanol exposure. These proteomic profiles provide valuable insight into the long-term molecular changes in the brain induced by early-ethanol exposure.

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Acknowledgments

The authors thank the University of Cape Town and the National Research Foundation (NRF) for their support. Any opinion, finding, conclusion, or recommendation expressed in this material is that of the authors, and the NRF does not accept any liability in this regard. In addition, the authors would like to thank the Faculty Research Committee of the University of Cape Town for awarding Postgraduate Publication Incentive Funding to PC Swart to complete research papers related to her Ph.D. thesis.

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Authors and Affiliations

  1. Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town, 7925, South Africa

    Patricia C. Swart, Vivienne A. Russell & Jacqueline J. Dimatelis

  2. Central Analytics Facility, Faculty of Medicine and Health Sciences, Stellenbosch University, Bellville, 7505, South Africa

    Nicolaas M. Vlok

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  1. Patricia C. Swart
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  2. Vivienne A. Russell
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  3. Nicolaas M. Vlok
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  4. Jacqueline J. Dimatelis
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Correspondence to Patricia C. Swart.

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Swart, P.C., Russell, V.A., Vlok, N.M. et al. Early-Ethanol Exposure Induced Region-Specific Changes in Metabolic Proteins in the Rat Brain: A Proteomics Study. J Mol Neurosci 65, 277–288 (2018). https://doi.org/10.1007/s12031-018-1097-z

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  • DOI: https://doi.org/10.1007/s12031-018-1097-z

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