title: Age-related changes in reactive oxygen species production in rat brain homogenates.
abstract: The generation of reactive oxygen species (ROS) and resultant oxidative stress have been implicated in the mechanism of brain dysfunction due to age-related neurodegenerative diseases or exposure to environmental chemicals. We have investigated intrinsic age-related differences in the ability of the various brain regions to generate ROS in the absence and presence of Fe(2)+. ROS production in crude brain homogenates from adult rats was linear with respect to time and tissue concentration, and was stimulated to a greater extent by Fe(2)+ than was TBARS production. ROS production was then determined in homogenates from cerebral cortex, striatum, hippocampus, and cerebellum of 7-day-old, 14-day-old, 21-day-old, adult (3-6-month old), and aged (24-month-old) rats using the fluorescent probe 2',7'-dichlorodihydrofluorescin (DCFH). Basal levels of ROS production were similar in 7-, 14-, and 21-day olds, increased in adults, and highest in aged rats, and did not differ between brain regions. ROS production was stimulated by Fe(2)+ (0. 3-30 microM) in a concentration-dependent manner in all brain regions. However, the stimulation of ROS production by Fe(2)+ varied with age. ROS production was greater in 14- and 21-day-old rats compared with adult and aged animals. ROS production in 7-day-old rats was decreased at low Fe(2)+ concentrations and increased at high Fe(2)+ concentrations compared to adult and aged rats. These data show that brain homogenates from neonatal rats respond differently to Fe(2)+, and suggest that developing animals may be more sensitive to oxidative stress in the brain after exposure to toxicants. Published by Elsevier Science Inc.
authors.affiliation: Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Driver
authors.forename: P R
authors.initials: PR
authors.lastname: Kodavanti
authors.forename: W R
authors.initials: WR
authors.lastname: Mundy
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D007501:Iron