Impact of Treadmill Running and Sex on Hippocampal Neurogenesis in the Mouse Model of Amyotrophic Lateral Sclerosis

Hippocampal neurogenesis in the subgranular zone (SGZ) of dentate gyrus (DG) occurs throughout life and is regulated by pathological and physiological processes. The role of oxidative stress in hippocampal neurogenesis and its response to exercise or neurodegenerative diseases remains controversial. The present study was designed to investigate the impact of oxidative stress, treadmill exercise and sex on hippocampal neurogenesis in a murine model of heightened oxidative stress (G93A mice). G93A and wild type (WT) mice were randomized to a treadmill running (EX) or a sedentary (SED) group for 1 or 4 wk. Immunohistochemistry was used to detect bromodeoxyuridine (BrdU) labeled proliferating cells, surviving cells, and their phenotype, as well as for determination of oxidative stress (3-NT; 8-OHdG). BDNF and IGF1 mRNA expression was assessed by in situ hybridization. Results showed that: (1) G93A-SED mice had greater hippocampal neurogenesis, BDNF mRNA, and 3-NT, as compared to WT-SED mice. (2) Treadmill running promoted hippocampal neurogenesis and BDNF mRNA content and lowered DNA oxidative damage (8-OHdG) in WT mice. (3) Male G93A mice showed significantly higher cell proliferation but a lower level of survival vs. female G93A mice. We conclude that G93A mice show higher hippocampal neurogenesis, in association with higher BDNF expression, yet running did not further enhance these phenomena in G93A mice, probably due to a ‘ceiling effect’ of an already heightened basal levels of hippocampal neurogenesis and BDNF expression

Streptozotocin Induced Diabetic Rats

Objective: The aim of this study was to investigate the effects of N(G)-nitro-L-arginine-metyl-ester (L-NAME) on visual evoked potentials (VEPs) and oxidative stress in streptozotocin (STZ)-induced diabetic rats.Methods: Wistar rats were assigned to one of four groups: control (C), diabetic (D), control + L-NAME (CN) and diabetic + L-NAME (DN). Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). Three days after the STZ injection, diabetes was confirmed by measuring tail blood glucose concentration. L-NAME was injected intraperitoneally to the CN and DN groups at a dose of 10 mg/kg/d for eight weeks. VEPs were recorded by a photic stimulator. Thiobarbituric acid-reactive substance (TBARS) as an index of oxidative stress, and nitrite levels were measured fluorometrically in the brain and retina tissues.Results: L-NAME treatment produced a significant decrease in nitrite levels with respect to the control group, and body weight, water and food consumption and plasma glucose concentrations of the diabetic rats. TBARS concentrations were increased in diabetic rats. Although L-NAME treatment significantly increased the retina and brain TBARS levels in CN group, decreased TBARS concentrations were found in diabetic rats. All VEP components were significantly increased in diabetic rats. L-NAME caused a significant delay in all VEP components in CN group.Conclusion: Our results clearly showed that although L-NAME improved clinical manifestations of diabetes such as polyphagia, polydipsia, and also plasma glucose and TBARS concentrations in brain and retina tissues, it did not alter prolonged VEP latencies in diabetic state

Streptozotocin Induced Diabetic Rats

Objective: The aim of this study was to investigate the effects of N(G)-nitro-L-arginine-metyl-ester (L-NAME) on visual evoked potentials (VEPs) and oxidative stress in streptozotocin (STZ)-induced diabetic rats.Methods: Wistar rats were assigned to one of four groups: control (C), diabetic (D), control + L-NAME (CN) and diabetic + L-NAME (DN). Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). Three days after the STZ injection, diabetes was confirmed by measuring tail blood glucose concentration. L-NAME was injected intraperitoneally to the CN and DN groups at a dose of 10 mg/kg/d for eight weeks. VEPs were recorded by a photic stimulator. Thiobarbituric acid-reactive substance (TBARS) as an index of oxidative stress, and nitrite levels were measured fluorometrically in the brain and retina tissues.Results: L-NAME treatment produced a significant decrease in nitrite levels with respect to the control group, and body weight, water and food consumption and plasma glucose concentrations of the diabetic rats. TBARS concentrations were increased in diabetic rats. Although L-NAME treatment significantly increased the retina and brain TBARS levels in CN group, decreased TBARS concentrations were found in diabetic rats. All VEP components were significantly increased in diabetic rats. L-NAME caused a significant delay in all VEP components in CN group.Conclusion: Our results clearly showed that although L-NAME improved clinical manifestations of diabetes such as polyphagia, polydipsia, and also plasma glucose and TBARS concentrations in brain and retina tissues, it did not alter prolonged VEP latencies in diabetic state

trained humans

Intravascular hemolysis is one of the most emphasized mechanisms for destruction of erythrocytes during and after physical activity. Exercise-induced oxidative stress has been proposed among the different factors for explaining exercise-induced hemolysis. The validity of oxidative stress following exhaustive cycling exercise on erythrocyte damage was investigated in sedentary and trained subjects before and after antioxidant vitamin treatment (A, C, and E) for 2 mo. Exercise induced a significant increase in thiobarbituric acid-reactive substance and protein carbonyl content levels in sedentary subjects and resulted in an increase of osmotic fragility and decrease in deformiability of erythrocytes, accompanied by. signs for intravascular hemolysis (increase in plasma hemoglobin concentration and decrease in haptoglobulin levels). Administration of antioxidant vitamins for 2 mo prevented exercise-induced oxidative stress (thiobarbituric acid-reactive substance, protein carbonyl content) and deleterious effects of exhaustive exercise on erythrocytes in sedentary subjects. Trained subjects' erythrocyte responses to exercise were different from those of sedentary subjects before antioxidant vitamin treatment. Osmotic fragility and deformability of erythrocytes, plasma hemoglobin concentration, and haptoglobulin levels were not changed after exercise, although the increased oxidative stress was observed in trained subjects. After antioxidant vitamin treatment, functional and structural parameters of erythrocytes were not altered in the trained group, but exercise-induced oxidative stress was prevented. Increased percentage of young erythrocyte populations was determined in trained subjects by density separation of erythrocytes. These findings suggest that the exercise-induced oxidative stress may contribute to exercise-induced hemolysis in sedentary humans.C1 Akdeniz Univ, Fac Med, Dept Physiol, TR-07070 Kampus, Antalya, Turkey.Akdeniz Univ, Sch Phys Educ & Sports, TR-07070 Kampus, Antalya, Turkey.Akdeniz Univ, Fac Med, Dept Biochem, TR-07070 Kampus, Antalya, Turkey.Pamukkale Univ, Fac Med, Dept Physiol, Denizli, Turkey