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Exercise Ameliorated Cognitive Dysfunction through Mitochondrial Remodeling in Alcohol Administrated C57BL/6 Mice
Author(s) -
Kelly Kimberly E.,
George Akash K.,
Behera Jyotirmaya,
Tyagi Neetu
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.842.7
Subject(s) - oxidative stress , mitochondrion , alcohol , intraperitoneal injection , saline , medicine , treadmill , alcohol consumption , endocrinology , chemistry , biochemistry
Alcohol consumption is a potent inducer of oxidative stress. Previous data indicate that alcohol consumption induces mitochondrial dysfunction and free radical production in mouse cerebral cortex. Exercise has been recommended by clinicians as a secondary protective therapy; however, its effect on brain functions through mitochondrial interventions has not been fully explored. Therefore, we hypothesized that exercise mitigates alcohol‐induced neurodegeneration and decline in cognitive function through mitochondrial remodeling. To test this hypothesis, we selected 10–12 weeks old male wild‐type mice (C57BL/6, WT), grouped as follows: 1) WT, 2) WT+ Alcohol, 3) WT+ Exercise, 4) WT+ Alcohol+ Exercise. Mice were given an intraperitoneal injection of EtOH (1.5g/kg BW) or saline solution every day for 12 weeks. The mice were exercised for 12 weeks on a treadmill with a controlled speed of 7 meters/min for the first week, the speed of 10 meters/min for the second week and 11 meters/min in the following weeks and a total of 330 meters every day. After each 110 meters mice were given rest of 10 minutes. Cognitive and behavior alterations were assessed by Novel Object Recognition, Passive Avoidance, and Y‐maze tests. Mitochondrial membrane potential and mitochondrial permeability changes were evaluated by flow cytometry. Our results suggest significant improvement in cognitive functions in exercised alcohol administrated group, as compared to non‐exercised alcohol administrated group. The involvement of mitochondrial remodeling in mice following exercise was further confirmed and we found there was a significant increase in ATP production, membrane potential, oxygen consumption, copy‐number as well as a decrease in reactive oxygen species when compared with non‐exercised alcoholic mice. Furthermore, a considerable reduction in TUNEL reactivity was determined in intact mitochondria isolated from the exercised group as compared to non‐exercised alcoholic mice. In addition, the effect of exercise on neuronal survival in the alcoholic brain was confirmed by Fluoro‐Jade C reactivity. Taken together, our results indicate a myriad of beneficiary effects of exercise over mitochondrial pathology during alcoholism. Furthermore, our findings suggest exercise mitigates neurodegeneration and cognitive dysfunction and thereby improving total mitochondrial function. Support or Funding Information This work was supported by NIH grant HL107640‐NT.