title: Enhanced defense against mitochondrial hydrogen peroxide attenuates age-associated cognition decline.
abstract: Increased mitochondrial hydrogen peroxide (H2O2) is associated with Alzheimer's disease and brain aging. Peroxiredoxin 3 (Prdx3) is the key mitochondrial antioxidant defense enzyme in detoxifying H2O2. To investigate the importance of mitochondrial H2O2 in age-associated cognitive decline, we compared cognition between aged (17-19 months) APP transgenic mice and APP/Prdx3 double transgenic mice (dTG) and between old (24 months) wild-type mice and Prdx3 transgenic mice (TG). Compared with aged APP mice, aged dTG mice showed improved cognition that was correlated with reduced brain amyloid beta levels and decreased amyloid beta production. Old TG mice also showed significantly increased cognitive ability compared with old wild-type mice. Both aged dTG mice and old TG mice had reduced mitochondrial oxidative stress and increased mitochondrial function. Moreover, CREB signaling, a signaling pathway important for cognition was enhanced in both aged dTG mice and old TG mice. Thus, our results indicate that mitochondrial H2O2 is a key culprit of age-associated cognitive impairment, and that a reduction of mitochondrial H2O2 could improve cognition by maintaining mitochondrial health and enhancing CREB signaling.
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Liuji
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Ren
authors.initials: R
authors.lastname: Na
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Geriatrics Research Education and Clinical Center, Research and Development Service, South Texas Veterans Health Care System, San Antonio, TX, USA. Electronic address: ran@uthscsa.edu.
authors.forename: Qitao
authors.initials: Q
authors.lastname: Ran
mesh_terms: D000375:Aging / Q000523:psychology*; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D018384:Oxidative Stress; D061105:Peroxiredoxin III / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; C516116:Prdx3 protein, mouse; D006861:Hydrogen Peroxide; D061105:Peroxiredoxin III
keywords: Alzheimer's disease; Beta-amyloid; Brain aging; Mitochondria; Mitochondrial H(2)O(2); Oxidative stress; Peroxiredoxin 3