Age-related changes in reactive oxygen species production in rat brain homogenates

• Published in: Neurotoxicology and teratology Vol. 22; no. 2; pp. 175 - 181
• Main Authors: Driver, Amy S., Kodavanti, Prasada Rao S., Mundy, William R.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-03-2000; Elsevier Science
• Subjects: Aging; Aging - metabolism; Animals; Antioxidant; Biological and medical sciences; Brain; Brain - growth & development; Brain - metabolism; Cerebellum - metabolism; Corpus Striatum - metabolism; Development; Embryology: invertebrates and vertebrates. Teratology; Female; Frontal Lobe - metabolism; Fundamental and applied biological sciences. Psychology; Hippocampus - metabolism; Iron - metabolism; Lipid Peroxidation; Male; Medical sciences; Miscellaneous; Rats; Rats, Long-Evans; Reactive oxygen species; Reactive Oxygen Species - metabolism; Teratology. Teratogens; Thiobarbituric Acid Reactive Substances - analysis; Toxicology; Development; Aging; Brain; Reactive oxygen species; Antioxidant; Cerebellum; Oxidative stress; Nervous system diseases; Oxygen; Rat; Toxicity; Rodentia; Central nervous system; Corpus striatum; Iron; Frontal cortex; In vitro; Vertebrata; Mammalia; Newborn animal; Animal; Central nervous system disease; Teratogen; Age; Hippocampus; Brain (vertebrata)
• ISSN: 0892-0362; 1872-9738
• DOI: 10.1016/S0892-0362(99)00069-0

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 μM) 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.