Makoto Ohno

Regular voluntary exercise cures stress-induced impairment of cognitive function and cell proliferation accompanied by increases in cerebral IGF-1 and GST activity in mice

Chronic stress impairs cognitive function and hippocampal neurogenesis. This impairment is attributed to increases in oxidative stress, which result in the accumulation of lipid peroxide. On the other hand, voluntary exercise enhances cognitive function, hippocampal neurogenesis, and antioxidant capacity in normal animals. However, the effects of voluntary exercise on cognitive function, neurogenesis, and antioxidants in stressed mice are unclear. This study was designed to investigate whether voluntary exercise cures stress-induced impairment of cognitive function accompanied by improvement of hippocampal neurogenesis and increases in antioxidant capacity. Stressed mice were exposed to chronic restraint stress (CRS), which consisted of 12h immobilization daily and feeding in a small cage, for 8 weeks. Exercised mice were allowed free access to a running wheel during their exposure to CRS. At the 6th week, cognitive function was examined using the Morris water maze (MWM) test. Daily voluntary exercise restored stress-induced impairment of cognitive function and the hippocampal cell proliferation of newborn cells but not cell survival. Voluntary exercise increased insulin-like growth factor 1 (IGF-1) protein and mRNA expression in the cerebral cortex and liver, respectively. In addition, CRS resulted in a significant increase in the number of 4-hydrosynonenal (4-HNE)-positive cells in the hippocampal dentate gyrus; whereas, voluntary exercise inhibited it and enhanced glutathione s-transferases (GST) activity in the brain. These findings suggest that voluntary exercise attenuated the stress-induced impairment of cognitive function accompanied by improvement of cell proliferation in the dentate gyrus. This exercise-induced improvement was attributed to exercise-induced enhancement of IGF-1 protein and GST activity in the brain.

Morinda citrifolia fruit reduces stress-induced impairment of cognitive function accompanied by vasculature improvement in mice

The purpose of this study was to investigate effects of Morinda citrifolia fruit juice, which is locally called Noni, on stress-induced impairment of cognitive function. Male ICR mice were divided into four groups: Control (C mice), Restraint stress (RS mice), Restraint+Noni (Noni mice), and Restraint+vitamin E (VE mice). The RS, Noni, and VE mice were subjected to 8h of chronic restraint stress (CRS) 6days a week for 6weeks. During this period, the Noni and VE mice were given a diet supplemented with either Noni or vitamin E, respectively. At Week 5, the mice were subjected to the Morris water maze (MWM) test to measure cognitive function. At Week 7, mouse brains were isolated for immunohistochemical analysis with BrdU or CD31 antibody to assess the proliferation of new cells and blood vessel density in the dentate gyrus of the hippocampus. The time taken to reach the platform in the MWM test was shorter in the Noni mice than in the RS mice on Day 16. Malondialdehyde (MDA ) level of the Noni mice was significantly higher than that of the C mice; however no difference was found in MDA levels between the VE and C mice. Blood vessel area was significantly lower in the R and VE mice than in the C mice; no difference was found between the C and Noni mice. These findings suggest that the administration of Noni fruit juice protects brains from stress-induced impairment of cognitive function and that this protective effect may be related to improvement in stress-induced decreases in blood vessel density in the hippocampal dentate gyrus.

Oral administration of inosine produces antidepressant-like effects in mice

Inosine, a breakdown product of adenosine, has recently been shown to exert immunomodulatory and neuroprotective effects. We show here that the oral administration of inosine has antidepressant-like effects in two animal models. Inosine significantly enhanced neurite outgrowth and viability of primary cultured neocortical neurons, which was suppressed by adenosine A1 and A2A receptor agonists. Oral administration of inosine to mice transiently increased its concentration in the brain and enhanced neuronal proliferation in the dentate gyrus, accompanied by phosphorylation of mitogen-activated protein kinase and increase in transcript level of brain-derived neurotrophic factor. In stress models, oral inosine prevented an increase in immobility time in forced swim test after chronically unexpected stress and mitigated a reduction in sucrose preference after chronic social defeat stress. These results indicate that oral administration of inosine has the potential to prevent depressive disorder via adenosine receptors.

Oral supplementation with melon superoxide dismutase extract promotes antioxidant defences in the brain and prevents stress-induced impairment of spatial memory

The purpose of this study was to investigate the effect of antioxidant ingestion on stress-induced impairment of cognitive memory. Male C57BL/6 mice were divided into four groups as follows: (1) control mice (C mice) fed in a normal cage without immobilization; (2) restraint-stressed (RS mice) fed in a small cage; (3) vitamin E mice (VE mice), mice were fed in a small cage with a diet supplemented with vitamin E; (4) GliSODin mice (GS mice) fed in a small cage with a diet supplemented with GliSODin. RS, VE and GS mice were exposed to 12 h of immobilization daily. Five weeks later, spatial learning was measured using the Morris Water Maze (MWM) test. After water maze testing, we performed immunohistochemical analysis using 4-hydroxy-2-noneral (4-HNE) and an anti-Ki67 antibody. 4-HNE is a marker of lipid peroxidation. RS mice showed impaired spatial learning performance and an increased number of 4-HNE-positive cells in the granule cell layer (GCL) of the hippocampal dentate gyrus when compared to C mice. Moreover, RS mice showed a decreased number of Ki67-positive cells in the subgranular zone (SGZ). GS mice showed better spatial learning memory than RS mice. The number of 4-HNE-positive cells in the GCL of GS mice was significantly less than that of RS mice. The number of Ki67-positive cells in the SGZ of GS mice was significantly greater than that of RS mice. These finding suggests that GliSODin prevents stress-induced impairment of cognitive function and maintains neurogenesis in the hippocampus through antioxidant activity.

Regular Moderate or Intense Exercise Prevents Depression-Like Behavior without Change of Hippocampal Tryptophan Content in Chronically Tryptophan-Deficient and Stressed Mice

Regular exercise has an antidepressant effect in human subjects. Studies using animals have suggested that the antidepressant effect of exercise is attributable to an increase of brain 5-hydroxytryptamine (5-HT); however, the precise mechanism underlying the antidepressant action via exercise is unclear. In contrast, the effect of 5-HT on antidepressant activity has not been clarified, in part because the therapeutic response to antidepressant drugs has a time lag in spite of the rapid increase of brain 5-HT upon administration of these drugs. This study was designed to investigate the contribution of brain 5-HT to the antidepressant effect of exercise. Mice were fed a tryptophan-deficient diet and stressed using chronic unpredictable stress (CUS) for 4 weeks with or without the performance of either moderate or intense exercise on a treadmill 3 days per week. The findings demonstrated that the onset of depression-like behavior is attributable not to chronic reduction of 5-HT but to chronic stress. Regular exercise, whether moderate or intense, prevents depression-like behavior with an improvement of adult hippocampal cell proliferation and survival and without the recovery of 5-HT. Concomitantly, the mice that exercised showed increased hippocampal noradrenaline. Regular exercise prevents the impairment of not long-term memory but short-term memory in a 5-HT-reduced state. Together, these findings suggest that: (1) chronic reduction of brain 5-HT may not contribute to the onset of depression-like behavior; (2) regular exercise, whether moderate or intense, prevents the onset of chronic stress-induced depression-like behavior independent of brain 5-HT and dependent on brain adrenaline; and (3) regular exercise prevents chronic tryptophan reduction-induced impairment of not long-term but short-term memory.

Effects of circuit low-intensity resistance exercise with slow movement on oxygen consumption during and after exercise

Abstract The purpose of this study was to examine oxygen consumption ([Vdot]O2) during and after a single bout of low-intensity resistance exercise with slow movement. Eleven healthy men performed the following three types of circuit resistance exercise on separate days: (1) low-intensity resistance exercise with slow movement: 50% of one-repetition maximum (1-RM) and 4 s each of lifting and lowering phases; (2) high-intensity resistance exercise with normal movement: 80% of 1-RM and 1 s each of lifting and lowering phases; and (3) low-intensity resistance exercise with normal movement: 50% of 1-RM and 1 s each of lifting and lowering phases. These three resistance exercise trials were performed for three sets in a circuit pattern with four exercises, and the participants performed each set until exhaustion. Oxygen consumption was monitored continuously during exercise and for 180 min after exercise. Average [Vdot]O2 throughout the exercise session was significantly higher with high- and low-intensity resistance exercise with normal movement than with low-intensity resistance exercise with slow movement (P < 0.05); however, total [Vdot]O2 was significantly greater in low-intensity resistance exercise with slow movement than in the other trials. In contrast, there were no significant differences in the total excess post-exercise oxygen consumption among the three exercise trials. The results of this study suggest that low-intensity resistance exercise with slow movement induces much greater energy expenditure than resistance exercise with normal movement of high or low intensity, and is followed by the same total excess post-exercise oxygen consumption for 180 min after exercise.

Changes in transverse relaxation time of quadriceps femoris muscles after active recovery exercises with different intensities

Abstract The purpose of this study was to examine the changes in the metabolic state of quadriceps femoris muscles using transverse relaxation time (T2), measured by muscle functional magnetic resonance (MR) imaging, after inactive or active recovery exercises with different intensities following high-intensity knee-extension exercise. Eight healthy men performed recovery sessions with four different conditions for 20 min after high-intensity knee-extension exercise on separate days. During the recovery session, the participants conducted a light cycle exercise for 20 min using a cycle (50%, 70% and 100% of the lactate threshold (LT), respectively: active recovery), and inactive recovery. The MR images of quadriceps femoris muscles were taken before the trial and after the recovery session every 30 min for 120 min. The percentage changes in T2 for the rectus femoris and vastus medialis muscles after the recovery session in 50%LT and 70%LT were significantly lower than those in either inactive recovery or 100%LT. There were no significant differences in those for vastus lateralis and vastus intermedius muscles among the four trials. The percentage changes in T2 of rectus femoris and vastus medialis muscles after the recovery session in 50%LT and 70%LT decreased to the values before the trial faster than those in either inactive recovery or 100%LT. Those of vastus lateralis and vastus intermedius muscles after the recovery session in 50%LT and 70%LT decreased to the values before the trial faster than those in 100%LT. Although the changes in T2 after active recovery exercises were not uniform in exercised muscles, the results of this study suggest that active recovery exercise with the intensities below LT are more effective to recover the metabolic state of quadriceps femoris muscles after intense exercise than with either intensity at LT or inactive recovery.

Intermittent intense exercise protects against cognitive decline in a similar manner to moderate exercise in chronically stressed mice

HighlightsRegular sessions of intermittent intense exercise prevented stress‐induced cognitive function losses in a similar manner to moderate exercise.Exercise effects on cognitive function may be closely related to survival of the newborn cell proliferation and angiogenesis in the hippocampus.Intense exercise helps maintain cognitive function in stressful situations in a similar manner to moderate exercise. ABSTRACT It is well known that regular low or mild exercise helps to improve and maintain cognition. On the other hand, ever thought many people prefer high‐intensity exercise (e.g., running, swimming, biking, soccer, basketball, etc.) to get rid of stress or improve their health, the previous studies reported that intense exercise either impairs cognition or has no effect on cognitive function. However, we previously showed that intermittent intense exercise prevents stress‐induced depressive behavior in mice in a similar manner to moderate exercise. On the basis of this finding, we investigated the effect of intermittent intense exercise on cognitive deficit in chronically stressed mice. A total of forty mice were evenly divided into control, stressed, stressed with moderate exercise, and stressed with intense exercise groups. The stressed mice were chronically exposed a restraint stress (10h/day, 6 days/week for 7 weeks). The exercised mice were subjected to intermittent intense or endurance moderate running on the treadmill three times a week. Cognition was evaluated using the Morris water maze test and the object recognition test. Chronic stress decreased cognition, and newborn cell survival and blood vessel density in the hippocampus. However, both regular intense and moderate exercise prevented decrease of cognition, improved newborn cell survival and blood vessel density. These findings suggest that intermittent intense exercise may protect against decrease of cognition in a similar manner to moderate exercise and that both exercise‐induced protection of decrease of cognition is closely related to newborn cell survival and angiogenesis in the hippocampus.