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Published on: August 30, 2007
Early-Ethanol Exposure Induced Region-Specific Changes in Metabolic Proteins in the Rat Brain: A Proteomics Study
Patricia C Swart1, Vivienne A Russell2, Nicolaas M Vlok3
1Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town, 7925, South Africa. swrpat003@myuct.ac.za.
Insights
Early alcohol exposure in rats alters brain proteins, affecting energy metabolism and structure. The dorsal hippocampus showed greater protein changes, suggesting higher susceptibility to prenatal alcohol
Area of Science:
- Neuroscience
- Biochemistry
- Toxicology
Background:
- Prenatal alcohol exposure causes cognitive and behavioral deficits.
- Understanding long-term molecular brain changes is crucial.
Purpose of the Study:
- To investigate the long-term effects of early ethanol exposure on brain proteins.
- To identify region-specific proteomic alterations in the prefrontal cortex and dorsal hippocampus.
Main Methods:
- Male Sprague-Dawley rat pups exposed to ethanol or saline during the third human trimester equivalent.
- Proteomic analysis using isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography-mass spectrometry (LC-MS) at postnatal day 31.
- Analysis focused on prefrontal cortex (PFC) and dorsal hippocampus (DH) tissues.
Main Results:
- Ethanol exposure altered NADH metabolism and oxidative phosphorylation in the PFC, while decreasing oxidative stress protection.
- In the DH, ethanol exposure reduced ATP synthesis and increased glycogen synthesis.
- Structural proteins were decreased in both PFC and DH, with more significant changes observed in the DH.
Conclusions:
- Early ethanol exposure induces region-specific long-term proteomic changes in the brain.
- The dorsal hippocampus appears more vulnerable to prenatal alcohol-induced molecular alterations.
- These findings offer insights into the molecular mechanisms underlying fetal alcohol spectrum disorders.
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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