Jung A Kim1, Roland R Roy1,2, Hui Zhong1, William A Alaynick3, Emi Embler3, Claire Jang1, Gabriel Gomez1, Takuma Sonoda1, Ronald M Evans3,4, V Reggie Edgerton1,2,5,6. 1. Department of Integrative Biology and Physiology, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, California, 90095-7239, USA. 2. Department of Neurosurgery, University of California, Los Angeles, Los Angeles, California, USA. 3. Gene Expression Laboratory, Salk Institute, La Jolla, California, USA. 4. Howard Hughes Medical Institute, La Jolla, California, USA. 5. Department of Neurobiology, University of California, Los Angeles, Los Angeles, California, USA. 6. Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA.
Abstract
INTRODUCTION: Skeletal muscle oxidative capacity decreases and fatigability increases after spinal cord injury. Transcription factor peroxisome proliferator-activated receptor δ (PPARδ) promotes a more oxidative phenotype. METHODS: We asked whether PPARδ overexpression could ameliorate these deficits in the medial gastrocnemius of spinal cord transected (ST) adult mice. RESULTS: Time-to-peak tension and half-relaxation times were longer in PPARδ-Con and PPARδ-ST compared with littermate wild-type (WT) controls. Fatigue index was 50% higher in PPARδ-Con than WT-Con and 70% higher in the PPARδ-ST than WT-ST. There was an overall higher percent of darkly stained fibers for succinate dehydrogenase in both PPARδ groups. CONCLUSIONS: The results indicate a conversion toward slower, more oxidative, and less fatigable muscle properties with overexpression of PPARδ. Importantly, the elevated fatigue resistance was maintained after ST, suggesting that enhanced PPARδ expression, and possibly small molecule agonists, could ameliorate the increased fatigability routinely observed in chronically paralyzed muscles.
INTRODUCTION: Skeletal muscle oxidative capacity decreases and fatigability increases after spinal cord injury. Transcription factor peroxisome proliferator-activated receptor δ (PPARδ) promotes a more oxidative phenotype. METHODS: We asked whether PPARδ overexpression could ameliorate these deficits in the medial gastrocnemius of spinal cord transected (ST) adult mice. RESULTS: Time-to-peak tension and half-relaxation times were longer in PPARδ-Con and PPARδ-ST compared with littermate wild-type (WT) controls. Fatigue index was 50% higher in PPARδ-Con than WT-Con and 70% higher in the PPARδ-ST than WT-ST. There was an overall higher percent of darkly stained fibers for succinate dehydrogenase in both PPARδ groups. CONCLUSIONS: The results indicate a conversion toward slower, more oxidative, and less fatigable muscle properties with overexpression of PPARδ. Importantly, the elevated fatigue resistance was maintained after ST, suggesting that enhanced PPARδ expression, and possibly small molecule agonists, could ameliorate the increased fatigability routinely observed in chronically paralyzed muscles.
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