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Abstract |
Multiple sclerosis (MS) is a complex neurodegenerative disease of the central nervous system (CNS) and dysfunctional mitochondria in neurons have been suggested to play a role. Hemoglobin is present in cortical neurons and levels are altered in MS cortex. The role of hemoglobin is unclear, however, hemoglobin β (Hbb) subunit levels are increased in mitochondrial fraction of MS cortex suggesting a potential role of hemoglobin in mitochondrial respiration. In fact, Hbb is tightly bound to chromatin and mediates a signaling mechanism that supports neuronal energetics involving the trimethylation of histone H3 on lysine 4 (H3K4me3), a histone mark that activates transcription of mitochondrial genes and increases mitochondrial respiratory capacity. We are excited by the potential influence that exercise may have on Hbb expression in the CNS and its impact on neuronal energetics. Thus, we compared exercise and sedentary lifestyles on neuronal Hbb expression and mitochondrial metabolism using Sprague Dawley rats. Rats aging 6-8 weeks-old were provided running wheels for a 7 week period. The Hbb expression was shown to be increased in exercised rats compared to sedentary rats. We also observed that increased Hbb expression correlated with an increase in basal neuronal mitochondrial respiration and increased mitochondrial respiration was linked to elevated levels of the neuronal mitochondrial metabolite N-acetylaspartate (NAA). Understanding regulatory mechanisms that impact Hbb expression and how Hbb supports neuronal mitochondria could lead to new therapeutic approaches (including exercise) to treat neurodegenerative diseases including MS, Alzheimer’s, and Parkinson’s where dysfunctional mitochondria contribute to disease activity.
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Contributor(s) |
Faculty Mentor
Dr. Ernest Freeman Dr. Jennifer McDonough
Alyx Weaver
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Modified Abstract |
Multiple sclerosis (MS) is a complex neurodegenerative disease of the central nervous system (CNS) and dysfunctional mitochondria in neurons have been suggested to play a role. Hemoglobin is present in cortical neurons and levels are altered in MS cortex. The role of hemoglobin is unclear, however, hemoglobin β (Hbb) subunit levels are increased in mitochondrial fraction of MS cortex suggesting a potential role of hemoglobin in mitochondrial respiration. Thus, we compared exercise and sedentary lifestyles on Hbb expression in rats. Understanding regulatory mechanisms that impact Hbb expression and how Hbb supports neuronal mitochondria could lead to new therapeutic approaches (including exercise) to treat neurodegenerative diseases including MS, Alzheimer’s, and Parkinson’s where dysfunctional mitochondria contribute to disease activity. |