title: Effect of high-intensity exercise on aged mouse brain mitochondria, neurogenesis, and inflammation.
abstract: In aged mice, we assessed how intensive exercise affects brain bioenergetics, inflammation, and neurogenesis-relevant parameters. After 8 weeks of a supra-lactate threshold treadmill exercise intervention, 21-month-old C57BL/6 mice showed increased brain peroxisome proliferator-activated receptor gamma coactivator-1α protein, mammalian target of rapamycin and phospho-mammalian target of rapamycin protein, citrate synthase messenger RNA, and mitochondrial DNA copy number. Hippocampal vascular endothelial growth factor A (VEGF-A) gene expression trended higher, and a positive correlation between VEGF-A and PRC messenger RNA levels was observed. Brain doublecortin, brain-derived neurotrophic factor, tumor necrosis factor-α, and CCL11 gene expression, as well as plasma CCL11 protein levels, were unchanged. Despite these apparent negative findings, a negative correlation between plasma CCL11 protein levels and hippocampal doublecortin gene expression was observed; further analysis indicated exercise may mitigate this relationship. Overall, our data suggest supra-lactate threshold exercise activates a partial mitochondrial biogenesis in aged mice, and a gene (VEGF-A) known to support neurogenesis. Our data are consistent with another study that found systemic inflammation in general, and CCL11 protein specifically, suppresses hippocampal neurogenesis. Our study supports the view that intense exercise above the lactate threshold may benefit the aging brain; future studies to address the extent to which exercise-generated lactate mediates the observed effects are warranted.
authors.affiliation: Department of Physical Therapy and Rehabilitation Sciences, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Lezi
authors.initials: L
authors.lastname: E
authors.affiliation: Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA; University of Kansas Alzheimer's Disease Center, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Burns
authors.affiliation: Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA; University of Kansas Alzheimer's Disease Center, University of Kansas Medical Center, Kansas City, KS, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: rswerdlow@kumc.edu.
authors.forename: Russell H
authors.initials: RH
authors.lastname: Swerdlow
mesh_terms: D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology*; D054413:Chemokine CCL11 / Q000097:blood; D002950:Citrate (si)-Synthase / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D018628:Gene Dosage; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007773:Lactates / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics; D009479:Neuropeptides / Q000378:metabolism; D001678:Organelle Biogenesis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000502:physiology
chemical_list: C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D004272:DNA, Mitochondrial; D000089622:Doublecortin Domain Proteins; D007773:Lactates; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D002950:Citrate (si)-Synthase; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
keywords: Aging brain; Exercise; Inflammation; Mitochondrial biogenesis; Neurogenesis