INTRODUCTION At rest, the brain uses about 1/5 of the total oxygen consumed by man to cover energy expenditure (about 240 kcal/kg organ mass/day as compared to about 30 kcal/kg whole body mass/day (1, 2). During physical exercise of moderate intensity, global and regional cerebral blood flow increase by 40 –70% to satisfy the increased metabolic demand for oxygen. The affected brain regions include motor-related structures and central command network (3). Increased oxygen consumption results in increased production of a variety of reactive oxygen species (ROS), e.g. superoxide anion, hydroxyl radicals, nitric oxide (NO) and singlet oxygen, due to oxidative phosphorylation-related electron leakage from mitochondrial transport chain (4-8). Being considered unavoidable by products of aerobic metabolism, ROS may cause oxidative damage to the cell components by impairing cellular energetics and modulating signaling pathways ("redox signaling") that lead to diverse acute and chronic changes in cellular environment dependent on the affected tissue (9). According to the most recent studies, about 1% of total oxygen consumed by the brain will form superoxide anion radical, with mitochondria (mainly complex 1), NADPH oxidase and cytosolic xanthine oxidase being most important contributors (10-12). The superoxide radical can be readily dismutated by superoxide dismutase (SOD; E.C. 1.15.1.1) to H 2 O 2 and singlet oxygen. H 2 O 2 is next converted by either catalase (CAT; E.C. 1.11.1.6) or glutathione peroxidase (GPx; E.C. 1.11.1.9) to H 2 O and O 2 (10, 11). The antioxidant enzymes CAT, GPx and SOD, and the ratio of reduced to oxidized glutathione (GSH/GSSG) are critical for protection against oxyradicals toxicity. Glutathione consumed (oxidized) in the GPx-mediated detoxification reaction is recycled back to GSH by glutathione reductase (GR; E.C. 1.6.4.2). The levels of glutathione and these antioxidant enzymes are much lower in the CNS as compared to erythrocytes and peripheral tissues (15, 16). JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2015, 66, 4, 539-547 www.jpp.krakow.pl M. CHALIMONIUK 1 , S. JAGSZ 2 , E. SADOWSKA-KREPA 2 , S.J. CHRAPUSTA 3 , B. KLAPCINSKA 2 , J. LANGFORT 4 DIVERSITY OF ENDURANCE TRAINING EFFECTS ON ANTIOXIDANT DEFENSES AND OXIDATIVE DAMAGE IN DIFFERENT BRAIN REGIONS OF ADOLESCENT MALE RATS 1 Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland; 2 Department of Physiological and Medical Sciences, The Jerzy Kukuczka Academy of Physical Education, Katowice, Poland; 3 Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland; 4 Department of Nutrition, The Jerzy Kukuczka Academy of Physical Education, Katowice, Poland Studies on the effect of physical activity on brain oxidative stress, performed mostly in adult rats, have shown that moderate aerobic activity increases resistance to oxidative stress and reduces cellular damage. These effects can greatly differ between various brain regions. The postnatal period of the highest brain sensitivity to various stimuli is adolescence. We hypothesized that endurance training will modify brain antioxidant barrier differently in various regions, depending on their role in locomotion. Therefore, we studied the effect of moderate intensity endurance training on the activities of selected antioxidant enzymes (superoxide dismutase, gluthathione peroxidase and catalase and the contents of thiobarbituric acid-reactive substances (the key index of lipid peroxidation) and glutathione in several brain regions with dissimilar relationship to locomotion, as well as in circulating blood. Additionally, we investigated the effect of the training on nitric oxide synthase activity that may be a major player in exercise-related oxidative stress in brain regions that are directly involved in the locomotion control and execution (the striatum, midbrain and cerebellum). The training significantly enhanced nitric oxide synthase activity only in the latter three regions. Surprisingly, it elevated the activities of all studied antioxidant enzymes (excepting gluthathione peroxidase) in the neocortex, while no appreciable change in these activities was found in either the cerebellum (except for elevated catalase activity), or the striatum, or the midbrain. The training also elevated total glutathione content (a key protector of brain proteins under the conditions of enhanced nitric oxide production) in the cerebellum and striatum, but not in the other regions. The observed brain changes greatly differed from those in circulating blood and did not prevent the training-related increases in oxidative damage as evidenced by elevations in cerebellar and striatal thiobarbituric acid-reactive substances. These data suggest an increased susceptibility of adolescent brain to enhanced physical activity-related oxidative stress. Key words: brain, anti-oxidative stress barrier, oxidative stress, endurance training, locomotion control, superoxide dismutase, gluthathione peroxidase, catalase, thiobarbituric acid-reactive substances, adolescence