Hostility, and total psychological stress, as well as stress-related mortality [14], and has been shown to improve depressive symptoms when used as an adjunct to medication [15]. In rodents, regular exercise was also shown to improve depressionlike behavior in chronically stressed mice [16]. Nevertheless, the mechanisms underlying the antidepressant effect of exercise are not understood. It is possible that exercise could contribute to rescue the lowered level of brain 5-HT in depressive patients; however, the relationship between exercise-induced improvement of depression and the level of brain 5-HT has yet to be elucidated. This study was designed to answer the following questions: (1) Is chronic tryptophan deficiency related to the onset and development of depression concomitantly with a deficit of cognitive function? (2) Are exercise-induced antidepressant effects related to brain 5-HT metabolism? To resolve these 16574785 issues, mice fed a TD diet were subjected to 4 weeks of chronic mild stress (CUS) with or without the performance of treadmill running at either moderate or high intensity. Concomitantly, the mice were subjected to behavioral tests to examine depression-like behavior and cognitive function. Our findings Fexinidazole biological activity demonstrated that the onset of depressionlike behavior is attributable not to TD but to chronic stress, whereas TD triggered the impairment of cognitive function, and that regular exercise, whether moderate or intense, prevents depression-like behavior concomitantly with an improvement of hippocampal neurogenesis and an increase of hippocampal noradrenaline, despite the recovery of brain 5-HT.subjected to a passive avoidance test (PAT) to examine learning and memory prior to CUS exposure. The protocol of PAT is described in the section on the behavior tests. After PAT, TD+CUS, TD+CUS+ME and TD+CUS+IE mice were BTZ043 cost exposed to 28 days of CUS according to a modified version of the method of Banasr et al. [18]. They were exposed to two stressors daily, as described in Table 1, in the morning and at night.3. ExerciseDuring the habituation period, all mice were subjected to 10 min of treadmill running at a treadmill speed of 10 m/min daily for five consecutive days to familiarize them with such running. During the CUS procedure, TD+CUS+ME and TD+CUS+IE mice were subjected to moderate or intense running on a treadmill three days per week at 4:00?:00 p.m. TD+CUS+ME mice were subjected to 1 h of running at a treadmill speed of 20 m/min. TD+CUS+IE mice were subjected to intense and intermittent exercise as follows: At first, mice performed running at a treadmill speed of 30 m/min for 1 min and then rested for 10 sec, which was defined as one set. After mice performed three sets of running at the same treadmill speed, the treadmill speed was increased to 35 m/min, and mice again performed three sets. In this way, the treadmill speed was increased at intervals of 5 m/min until the mice were exhausted.4. 5-bromo-2-deoxyuridine (BrdU) InjectionTwo weeks before the sacrifice of the animals, BrdU dissolved in sterilized saline was intraperitoneally injected into all mice at 50 mg/kg body weight for five consecutive days at 24-hour intervals in order to evaluate the survival of newly born cells.Materials and Methods 1. Animals and DietAll experimental procedures and animal treatments were performed in accordance with the guidelines of the laboratory animal manual of Nippon Medical School. Male C57BL/6J mice (Sankyo Lab Service, Tokyo, Japan), a.Hostility, and total psychological stress, as well as stress-related mortality [14], and has been shown to improve depressive symptoms when used as an adjunct to medication [15]. In rodents, regular exercise was also shown to improve depressionlike behavior in chronically stressed mice [16]. Nevertheless, the mechanisms underlying the antidepressant effect of exercise are not understood. It is possible that exercise could contribute to rescue the lowered level of brain 5-HT in depressive patients; however, the relationship between exercise-induced improvement of depression and the level of brain 5-HT has yet to be elucidated. This study was designed to answer the following questions: (1) Is chronic tryptophan deficiency related to the onset and development of depression concomitantly with a deficit of cognitive function? (2) Are exercise-induced antidepressant effects related to brain 5-HT metabolism? To resolve these 16574785 issues, mice fed a TD diet were subjected to 4 weeks of chronic mild stress (CUS) with or without the performance of treadmill running at either moderate or high intensity. Concomitantly, the mice were subjected to behavioral tests to examine depression-like behavior and cognitive function. Our findings demonstrated that the onset of depressionlike behavior is attributable not to TD but to chronic stress, whereas TD triggered the impairment of cognitive function, and that regular exercise, whether moderate or intense, prevents depression-like behavior concomitantly with an improvement of hippocampal neurogenesis and an increase of hippocampal noradrenaline, despite the recovery of brain 5-HT.subjected to a passive avoidance test (PAT) to examine learning and memory prior to CUS exposure. The protocol of PAT is described in the section on the behavior tests. After PAT, TD+CUS, TD+CUS+ME and TD+CUS+IE mice were exposed to 28 days of CUS according to a modified version of the method of Banasr et al. [18]. They were exposed to two stressors daily, as described in Table 1, in the morning and at night.3. ExerciseDuring the habituation period, all mice were subjected to 10 min of treadmill running at a treadmill speed of 10 m/min daily for five consecutive days to familiarize them with such running. During the CUS procedure, TD+CUS+ME and TD+CUS+IE mice were subjected to moderate or intense running on a treadmill three days per week at 4:00?:00 p.m. TD+CUS+ME mice were subjected to 1 h of running at a treadmill speed of 20 m/min. TD+CUS+IE mice were subjected to intense and intermittent exercise as follows: At first, mice performed running at a treadmill speed of 30 m/min for 1 min and then rested for 10 sec, which was defined as one set. After mice performed three sets of running at the same treadmill speed, the treadmill speed was increased to 35 m/min, and mice again performed three sets. In this way, the treadmill speed was increased at intervals of 5 m/min until the mice were exhausted.4. 5-bromo-2-deoxyuridine (BrdU) InjectionTwo weeks before the sacrifice of the animals, BrdU dissolved in sterilized saline was intraperitoneally injected into all mice at 50 mg/kg body weight for five consecutive days at 24-hour intervals in order to evaluate the survival of newly born cells.Materials and Methods 1. Animals and DietAll experimental procedures and animal treatments were performed in accordance with the guidelines of the laboratory animal manual of Nippon Medical School. Male C57BL/6J mice (Sankyo Lab Service, Tokyo, Japan), a.
