title: Physical exercise improves brain cortex and cerebellum mitochondrial bioenergetics and alters apoptotic, dynamic and auto(mito)phagy markers.
abstract: We here investigate the effects of two exercise modalities (endurance treadmill training-TM and voluntary free-wheel activity-FW) on the brain cortex and cerebellum mitochondrial bioenergetics, permeability transition pore (mPTP), oxidative stress, as well as on proteins involved in mitochondrial biogenesis, apoptosis, and quality control. Eighteen male rats were assigned to sedentary-SED, TM and FW groups. Behavioral alterations and ex vivo brain mitochondrial function endpoints were assessed. Proteins involved in oxidative phosphorylation (OXPHOS, including the adenine nucleotide translocator), oxidative stress markers and regulatory proteins (SIRT3, p66shc, UCP2, carbonyls, MDA, -SH, aconitase, Mn-SOD), as well as proteins involved in mitochondrial biogenesis (PGC1α, TFAM) were evaluated. Apoptotic signaling was measured through quantifying caspase 3, 8 and 9-like activities, Bax, Bcl2, CypD, and cofilin expression. Mitochondrial dynamics (Mfn1/2, OPA1 and DRP1) and auto(mito)phagy (LC3II, Beclin1, Pink1, Parkin, p62)-related proteins were also measured by Western blotting. Only the TM exercise group showed increased spontaneous alternation and exploratory activity. Both exercise regimens improved mitochondrial respiratory activity, increased OXPHOS complexes I, III and V subunits in both brain subareas and decreased oxidative stress markers. Increased resistance to mPTP and decreased apoptotic signaling were observed in the brain cortex from TM and in the cerebellum from TM and FW groups. Also, exercise increased the expression of proteins involved in mitochondrial biogenesis, autophagy and fusion, simultaneous with decreased expression of mitochondrial fission-related protein DRP1. In conclusion, physical exercise improves brain cortex and cerebellum mitochondrial function, decreasing oxidative stress and apoptotic related markers. It is also possible that favorable alterations in mitochondrial biogenesis, dynamics and autophagy signaling induced by exercise contributed to increased mitochondrial plasticity leading to a more robust phenotype.
authors.affiliation: CIAFEL - Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal. Electronic address: inesmaleixo@hotmail.com.
authors.forename: I
authors.initials: I
authors.lastname: Marques-Aleixo
authors.affiliation: CIAFEL - Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: E
authors.initials: E
authors.lastname: Santos-Alves
authors.affiliation: CIAFEL - Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: M M
authors.initials: MM
authors.lastname: Balça
authors.affiliation: CIAFEL - Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Rizo-Roca
authors.affiliation: CNC - Centre for Neuroscience and Cell Biology, University of Coimbra, Portugal; Institute of Physiology, Faculty of Medicine, University of Coimbra, Portugal.
authors.forename: P I
authors.initials: PI
authors.lastname: Moreira
authors.affiliation: CNC - Centre for Neuroscience and Cell Biology, University of Coimbra, UC Biotech Building, Biocant Park, Cantanhede, Portugal.
authors.forename: P J
authors.initials: PJ
authors.lastname: Oliveira
authors.affiliation: CIAFEL - Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Magalhães
authors.affiliation: CIAFEL - Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Ascensão
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002531:Cerebellum / Q000502:physiology*; D002540:Cerebral Cortex / Q000503:physiopathology*; D004734:Energy Metabolism / Q000502:physiology*; D005080:Exercise Test; D005106:Exploratory Behavior / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D050050:Protein Carbonylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D009498:Neurotoxins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D020169:Caspases; D002118:Calcium
keywords: brain; exercise; mitochondrial metabolism; mitochondrial quality control