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Exercise-induced changes of gene expression in the cerebellum of aged mice
Affiliation:1. Massachusetts General Hospital, Harvard Medical School, Boston, United States of America;2. Broad Institute of MIT and Harvard, Cambridge, Boston, United States of America;3. Harvard Stem Cell Institute, Cambridge, MA, United States of America;4. Henry and Allison McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, United States of America
Abstract:PurposeExercise has been prescribed to the elderly based on its effect on increasing muscle strength and protein synthesis that prevent sense of balance and/or cognitive functions. However, a few molecular mechanism researches has been conducted on how the vestibular organs, cerebellum, and hippocampus, which are responsible for the deterioration and balance of spatial learning memory due to aging, are affected by exercise.MethodsThe 9-week old and 84-week old C57Bl/6 were assigned randomly to Young-Control (YC), Young-Exercise (YE), Old-Control (OC) and Old-Exercise (OE) groups for 4 -week treadmill running. A Rotarod test was used to evaluate motor coordination function. Moreover, a high-throughput whole transcript expression RNA array approach was applied to the cerebellum of aged mice to explain the novel molecular mechanism of beneficial effect of exercise.ResultsAs results, the motor coordination function was significantly improved in exercise-aged mice. The RNA sequencing analysis showed that the expression of cerebellar genes was significantly changed by aging rather than exercise. Especially, Cers1 was up-regulated in sedentary aged mice and down-regulated in exercise aged mice. Fumonisin B1, inhibition of Cers1, mitigates neuronal cell death induced by doxorubicin.ConclusionThese results provide unraveling specific transcripts and understanding of the exercise-related cerebellum transcriptome in aged mice. Well-designed exercise program might prevent the motor coordination defect in aged model, which development of the exercise protocol for elderly population based on these markers.
Keywords:Exercise  Aging  Cerebellum  Motor coordination  RNA sequencing  CerS1
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