Abstract P116: Exercise Ameliorated Cognitive Impairment Through ER Stress Mitigation in Alcohol Treated Exercise Ameliorated Cognitive Impairment Through Er Stress Mitigation in Alcohol Treated C57bl/6 Male Mice

Abstract

Alcohol consumption is a potent inducer of oxidative stress (OS). Oxidative stress cause disturbance of endoplasmic reticulum (ER) homeostasis, that triggers ER stress (ERS), cause neuronal damage in the brain. Our 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 ER stress has not been fully explored. Therefore, we hypothesized that exercise improves Alcohol-induced neurodegeneration and decline in cognitive function through ER stress mitigation. 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 Alcohol (1.5g/kg BW) or saline solution every day for 8 weeks. The mice were exercised for 8 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. Our result showed there is a significantly impaired cognitive and behavior functions (600.00 ± 0.00 vs 480 ± 20.00, P<0.05) in Alcohol-treated group compared to WT control mice. However exercised significantly improved (0.37 ± 0.05 vs 0.63 ± 0.04 P<0.01) these functions as compared to Alcohol-treated group. Also, we observed an elevated blood pressure in the Alcohol-treated group (123.50 ± 1.17) and exercise brought that to the normal level (108.98 ± 4.47, P<0.01). In addition, the effect of exercise on neuronal survival in the Alcohol-treated mouse brain was confirmed by a decrease in by fluoro-jade C reactivity. Taken together, our results indicate a myriad of beneficiary effects of exercise over ER mitigation in Alcohol-treated mice. Furthermore, our findings suggest exercise alleviates neurodegeneration and cognitive dysfunction and thereby improving total brain function. This work was supported by NIH grant HL107640-NT