Adolescent Binge Alcohol Exposure Affects the Brain Function Through Mitochondrial Impairment
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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. 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.
KeywordsAlcohol Binge drinking Mitochondria Oxidative stress Synaptic dysfunction
This work was supported by FONDECYT: 1140968 and 1170441 (to RAQ), 11121206 (to WC), 11121133 and 1160710 (to JAO), 11150308 (to JML), Proyecto de Cooperación Internacional (PCI), BMBF 20150065 (to WC), and Anillo ACT1411 (to RAQ, WC, JAO, and JML).
CTR, RAQ, WC, JAO, and JML designed and coordinated the study. CTR, FJC, RMG, and CA conducted most of the experiments and performed the statistical analyses. CTR, WC, and RAQ wrote the manuscript. All authors read and approved the final manuscript.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
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