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

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 t he 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.
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research