title: Age- and brain region-specific differences in mitochondrial bioenergetics in Brown Norway rats.
abstract: Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bioenergetic parameters in 5 brain regions (brain stem [BS], frontal cortex, cerebellum, striatum, hippocampus [HIP]) of 4 diverse age groups (1 month [young], 4 months [adult], 12 months [middle-aged], 24 months [old age]) to understand age-related differences in selected brain regions and their possible contribution to age-related chemical sensitivity. Mitochondrial bioenergetic parameters and enzyme activities were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5/group). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State III respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12, and 24-months age groups. Activities of mitochondrial pyruvate dehydrogenase complex and electron transport chain complexes I, II, and IV enzymes were also age and brain region specific. In general, changes associated with age were more pronounced with enzyme activities declining as the animals aged (young > adult > middle-aged > old age). These age- and brain region-specific observations may aid in evaluating brain bioenergetic impact on the age-related susceptibility to environmental chemical stressors.
authors.affiliation: Spinal Cord and Brain Injury Research Center, Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA.
authors.forename: Jignesh D
authors.initials: JD
authors.lastname: Pandya
authors.affiliation: Genetic and Cellular Toxicology Branch, Integrated Systems Toxicology Division, NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA.
authors.forename: Joyce E
authors.initials: JE
authors.lastname: Royland
authors.affiliation: Neurotoxicology Branch, Toxicity Assessment Division, NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: MacPhail
authors.affiliation: Spinal Cord and Brain Injury Research Center, Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Sullivan
authors.affiliation: Neurotoxicology Branch, Toxicity Assessment Division, NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA. Electronic address: kodavanti.prasada@epa.gov.
authors.forename: Prasada Rao S
authors.initials: PR
authors.lastname: Kodavanti
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000166:cytology*; D008928:Mitochondria / Q000201:enzymology; D001678:Organelle Biogenesis; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats
chemical_list: D011768:Pyruvate Dehydrogenase Complex
keywords: Aging; Bioenergetics; Brain regions; Enzyme activity; Mitochondria; Rats; Susceptibility