Jacob L. Brown1, Richard A. Perry, Jr1., Kevin L. Shimkus2,David E. Lee1, Megan E. Rosa1, Jessica M. Cardin2, Lemuel A. Brown1, Elizabeth K. McBee1, Yasaman Sharazi-Fard2, Harry Hogan2, James D. Fluckey2, Tyrone A. Washington1 & Nicholas P.Greene1,2

1University of Arkansas, Fayetteville, Arkansas. 2Texas A&M University, College Station, Texas

Muscular disuse affects a great number of people have sedentary lifestyles and/or chronic disease. Disuse has been shown to cause severe muscular atrophy and to disrupt mitochondrial quality. PURPOSE: To examine if disuse affects mitochondrial biogenesis, and if resistance exercise following bouts of unloading can promote biogenesis. METHODS: Sprague-Dawley rats were subjected to chronic disuse atrophy by hindlimb unloading (28-d, 1HU) followed by ambulatory recovery (56-d) with (1HU+EX) and without (1HU+REC) resistance exercise. To mimic repeated bouts of disuse animals were subjected to a second bout of HU (28-d, 2HU) and again allowed ambulatory recovery with (2HU+EX) or without (2HU+REC) resistance exercise. Control (CON) animals were allowed normal cage activity throughout. Samples were analyzed for Pgc-1α, Tfam, Nrf2 and Pparα gene expression by real time RT-PCR. To test if disuse impacted mitochondrial biogenesis regulators a T-Test was performed between CON and 1HU groups, to test impact of reloading and exercise data were analyzed by one-way ANOVA across all groups with α set at PRESULTS: Pgc-1α expression decreased by 59% (p=0.042) and Nrf2 by 75% (p=0.047) following disuse (1HU) compared to CON. 1HU+Ex showed a 280% increase in Pparα expression (p=0.005) as well as a 278% increase in Tfam expression (p=0.013) compared to CON. Pgc-1α, Pparα, and Tfam displayed a greater increase in expression with exercise recovery (1HU+Ex) than without (1HU+Rec). Pgc-1α showed an 80% increase in expression (p=0.05), Pparα showed a 208% increase in expression (p=0.01), and Tfam showed a 195% increase in expression (p=0.01) when comparing 1HU+Ex and 1HU+Rec. Nrf2 decreased by 61% (p=0.008) with 2HU. Expression of other biogenesis markers was not changed in the 2HU group. Neither 2HU+Ex nor 2HU+Rec were able to attenuate the loss of Nrf2 expression. CONCLUSION: A single bout of disuse significantly decreases the expression of Pgc-1α and Nrf2. 1HU+Ex promotes mitochondrial biogenesis more than 1HU+Rec. Multiple bouts of disuse decreases the expression of Nrf2. 2HU+Ex and 2HU+Rec does not attenuate the loss of Nrf2 expression. More research needs to be conducted to examine other aspects of mitochondrial quality such as mitochondrial dynamics and autophagy.

Funded By National Space Biomedical Research Institute

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