Adolescent Binge Alcohol Exposure Affects the Brain Function Through Mitochondrial Impairment

• Published in: Molecular neurobiology Vol. 55; no. 5; pp. 4473 - 4491
• Main Authors: Tapia-Rojas, Cheril, Carvajal, Francisco J., Mira, Rodrigo G., Arce, Camila, Lerma-Cabrera, José Manuel, Orellana, Juan A., Cerpa, Waldo, Quintanilla, Rodrigo A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-05-2018; Springer Nature B.V
• Subjects: Adenosine Triphosphate - biosynthesis; Adolescent; Adolescents; Alcohol use; Alcoholic beverages; Animals; Binge drinking; Binge Drinking - pathology; Binge Drinking - physiopathology; Bioenergetics; Biomedical and Life Sciences; Biomedicine; Brain; Brain - pathology; Brain - physiopathology; Cell Biology; Cognition; Drinking behavior; Drug abuse; Ethanol; Exposure; GA-Binding Protein Transcription Factor - metabolism; Hippocampal plasticity; Hippocampus; Hippocampus - pathology; Hippocampus - physiopathology; Humans; Inflammation; Inflammation - pathology; Inflammation - physiopathology; Learning; Male; Membrane permeability; Memory; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrial Dynamics; Mitochondrial Membrane Transport Proteins - metabolism; Mitochondrial Permeability Transition Pore; Neurobiology; Neurology; Neurosciences; Oxidative Stress; Plasticity; Rats; Rats, Sprague-Dawley; Rodents; Synaptic plasticity; Synaptic Transmission; Task Performance and Analysis; Binge drinking; Oxidative stress; Alcohol; Mitochondria; Synaptic dysfunction
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-017-0613-4

In the young population, binge drinking is a pattern of problematic alcohol consumption, characterized by a short period of heavy drinking followed by abstinence which is frequently repeated over time. This drinking pattern is associated with mental problems, use of other drugs, and an increased risk of excessive alcohol intake during adulthood. However, little is known about the effects of binge drinking on brain function in adolescents and its neurobiological impact during the adulthood. In the present study, we evaluated the effects of alcohol on hippocampal memory, synaptic plasticity, and mitochondrial function in adolescent rats after a binge drinking episode in vivo
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These effects were analyzed at 1, 3, or 7 weeks post alcohol exposure. Our results showed that binge-like ethanol pre-treated (BEP) rats exhibited early alterations in learning and memory tests accompanied by an impairment of synaptic plasticity that was total and partially compensated, respectively. These changes could be attributed to a rapid increase in oxidative damage and a late inflammatory response induced by post ethanol exposure. Additionally, BEP alters the regulation of mitochondrial dynamics and modifies the expression of mitochondrial permeability transition pore (mPTP) components, such as cyclophilin D (Cyp-D) and the voltage-dependent anion channel (VDAC). These mitochondrial structural changes result in the impairment of mitochondrial bioenergetics, decreasing ATP production progressively until adulthood. These results strongly suggest that teenage alcohol binge drinking impairs the function of the adult hippocampus including memory and synaptic plasticity as a consequence of the mitochondrial damage induced by alcohol and that the recovery of hippocampal function could implicate the activation of alternative pathways that fail to reestablish mitochondrial function.