title: Differential sensitivity of prefrontal cortex and hippocampus to alcohol-induced toxicity.
abstract: The prefrontal cortex (PFC) is a brain region responsible for executive functions including working memory, impulse control and decision making. The loss of these functions may ultimately lead to addiction. Using histological analysis combined with stereological technique, we demonstrated that the PFC is more vulnerable to chronic alcohol-induced oxidative stress and neuronal cell death than the hippocampus. This increased vulnerability is evidenced by elevated oxidative stress-induced DNA damage and enhanced expression of apoptotic markers in PFC neurons. We also found that one-carbon metabolism (OCM) impairment plays a significant role in alcohol toxicity to the PFC seen from the difference in the effects of acute and chronic alcohol exposure on DNA repair and from exaggeration of the damaging effects upon additional OCM impairment in mice deficient in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR). Given that damage to the PFC leads to loss of executive function and addiction, our study may shed light on the mechanism of alcohol addiction.
authors.affiliation: Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.
authors.forename: Anna-Kate
authors.initials: AK
authors.lastname: Fowler
authors.affiliation: Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Thompson
authors.affiliation: Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.
authors.forename: Lixia
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.
authors.forename: Marisela
authors.initials: M
authors.lastname: Dagda
authors.affiliation: Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.
authors.forename: Janet
authors.initials: J
authors.lastname: Dertien
authors.affiliation: Laboratory of Clinical Investigation, NIA, National Institutes of Health, Baltimore, Maryland, United States of America.
authors.forename: Katina Sylvestre S
authors.initials: KS
authors.lastname: Dossou
authors.affiliation: Laboratory of Clinical Investigation, NIA, National Institutes of Health, Baltimore, Maryland, United States of America.
authors.forename: Ruin
authors.initials: R
authors.lastname: Moaddel
authors.affiliation: Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Bergeson
authors.affiliation: Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.
authors.forename: Inna I
authors.initials: II
authors.lastname: Kruman
mesh_terms: D000208:Acute Disease; D000437:Alcoholism / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D002908:Chronic Disease; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D000431:Ethanol / Q000633:toxicity*; D015870:Gene Expression; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006710:Homocysteine / Q000378:metabolism; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D018384:Oxidative Stress; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013238:Stereotaxic Techniques
chemical_list: D015415:Biomarkers; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D006710:Homocysteine; D000431:Ethanol; D042965:Methylenetetrahydrofolate Reductase (NADPH2)