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Molecular Neurobiology

, Volume 55, Issue 5, pp 4473–4491 | Cite as

Adolescent Binge Alcohol Exposure Affects the Brain Function Through Mitochondrial Impairment

  • Cheril Tapia-Rojas
  • Francisco J. Carvajal
  • Rodrigo G. Mira
  • Camila Arce
  • José Manuel Lerma-Cabrera
  • Juan A. Orellana
  • Waldo Cerpa
  • Rodrigo A. Quintanilla
Article

Abstract

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.

Keywords

Alcohol Binge drinking Mitochondria Oxidative stress Synaptic dysfunction 

Notes

Acknowledgements

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).

Author Contributions

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.

Supplementary material

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Fig. S1

Ethanol binge-like administration induces oxidative damage in the brain of adolescent rats. Representative images from immunofluorescence of the CA3 region of the hippocampus obtained from animals at three different time points: 1 week after injections (n = 3), 3 weeks after injections (n = 3) and 7 weeks after injections (n = 3). Hoechst staining was used to identify the nuclei, 8-hydroxyguanine (DNA damage) immunoreactivity and merge images are shown. Quantification of images shows a comparison between the 3 different times after ethanol treatment. There was a decrease in 8-hydroxyguanine immunoreactivity 1 week after ethanol injections, and there was no difference between the control and ethanol group at the other measured times. *p < 0.05; n.s not significant. Bars represent the mean ± SEM. *p < 0.05. (GIF 2.0 mb)

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Fig. S2

Ethanol binge-like administration not alters the mitochondrial mass in the brain of adolescent rats. Representative images obtained from SP or BEP rats. 25 μM coronal slices of unfixed tissue were incubated with MitoTracker Green FM for 45 min a 37 °C. Fluoroshield Mounting Medium with DAPI was also used. The relative intensity shows no significant differences between SP and BEP rats in CA1, CA3 and Dentate Gyrus. The number of cells per field was similar in both control and treated rats. High Resolution Image (GIF 1.45 mb)

12035_2017_613_MOESM2_ESM.tiff (8.1 mb)
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12035_2017_613_Fig12_ESM.gif (1.9 mb)
Fig. S3

Ethanol binge-like administration not induces changes in the number of cells in the hippocampus of treated rats. Representative images of Nissl stain to evaluate the cell density in the CA1, CA3 and DG region from the hippocampus. Analysis reveals similar density of cells in both SP and BEP rats in all regions measured.(GIF 1.88 mb)

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12035_2017_613_Fig13_ESM.gif (276 kb)
Table S1

Ethanol binge-like administration no induces changes in the locomotor activity. Swimming rate in the MWM, average speed in the NOR and average travel speed in the SI task in both SP and BEP rats. No significant differences were observed between the experimental groups. (GIF 275 kb)

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High Resolution Image (TIFF 8.14 mb)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Cheril Tapia-Rojas
    • 1
    • 2
  • Francisco J. Carvajal
    • 1
    • 3
  • Rodrigo G. Mira
    • 1
    • 3
  • Camila Arce
    • 1
    • 3
  • José Manuel Lerma-Cabrera
    • 1
  • Juan A. Orellana
    • 1
    • 4
  • Waldo Cerpa
    • 1
    • 3
  • Rodrigo A. Quintanilla
    • 1
    • 2
  1. 1.Centro de Investigación y Estudio del Consumo de Alcohol en Adolescentes (CIAA)SantiagoChile
  2. 2.Laboratory of Neurodegenerative Diseases, CIBUniversidad Autónoma de ChileSantiagoChile
  3. 3.Laboratorio de Función y Patología Neuronal, Departamento de Biología Celular y Molecular, Facultad de Ciencias BiológicasPontificia Universidad Católica de ChileSantiagoChile
  4. 4.Departamento de Neurología, Escuela de MedicinaPontificia Universidad Católica de Chile SantiagoSantiagoChile

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