Neurogenic effect of exercise via the thioredoxin-1/ extracellular regulated kinase/ß-catenin signaling pathway mediated by ß2-adrenergic receptors in chronically stressed dentate gyrus.

PURPOSE: Chronic stress is a precipitating factor for depression, whereas exercise is beneficial for both the mood and cognitive process. The current study demonstrates the anti-depressive effects of regular exercise and the mechanisms linked to hippocampal neurogenesis. METHODS: Mice were subjected to 14 consecutive days of restraint, followed by 3 weeks of treadmill running, and were then subjected to behavioral tests that included the forced swimming and Y-maze tests. Protein levels were assessed using western blot analysis and newborn cells were detected using 5-bromo-2'-deoxyuridine (BrdU). RESULTS: Three weeks of treadmill running ameliorated the behavioral depression caused by 14 days of continuous restraint stress. The exercise regimen enhanced BrdU-labeled cells and class III ß-tubulin levels in the hippocampal dentate gyrus, as well as those of thioredoxin-1 (TRX-1) and synaptosomal ß2-adrenergic receptors (ß2-AR) under stress. In vitro experiments involving treatment with recombinant human TRX-1 (rhTRX-1) augmented the levels of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2), nuclear ß-catenin, and proliferating cell nuclear antigens, which were previously inhibited by U0216 and FH535 (inhibitors of ERK1/2 and ß-catenin/T cell factor-mediated transcription, respectively). The hippocampal neurogenesis elicited by a 7-day exercise regimen was abolished by a selective inhibitor of ß2-AR, butoxamine. CONCLUSION: These results suggest that TRX-1-mediated hippocampal neurogenesis by ß2-AR function is a potential mechanism underlying the psychotropic effect of exercise.

The effects of peripherally-subacute treatment with irisin on hippocampal dendritogenesis and astrocyte-secreted factors.

PURPOSE: Fibronectin type III domain containing 5 (FNDC5)/irisin is an exercise-induced myokine, which contributes to cognitive functions. However, the relationship between the neuroprotective effects of FNDC5/irisin and hippocampal dendritic remodeling and astrocyte-secreted factors remains unclear. Therefore, we explored whether subchronic recombinant irisin treatment affected hippocampal morphology and some astrocyte-derived molecules. METHODS: Mice were intraperitoneally injected with irisin (0.5 µg/kg/day) for seven days, followed by their sacrifice two days later. Hippocampal morphometric parameters were analyzed and pgc-1a, fndc5, bdnf, and some astrocyte-derived factors mRNA levels were measured. RESULTS: Dendritic length, arborization, and spine density were enhanced by irisin regimen in hippocampal CA1 and CA3 areas. Hippocampal pgc-1a, fndc5, and bdnf mRNA levels were significantly increased by irisin treatment. Moreover, hevin mRNA levels were significantly enhanced, whereas tgf-b1 levels downregulated by irisin treatment. CONCLUSION: FNDC5/irisin has dendritogenic activity probably through hevin induction and TGF-ß1 suppression.

The Association between 10-Year Atherosclerotic Cardiovascular Diseases Risk Score Calculated Using 2013 American College of Cardiology/American Heart Association Guidelines and Serum 25-Hydroxyvitamin D Level among Aged 40-79 Years in Korea: The Sixth Korea National Health and Nutrition Examination Surveys.

BACKGROUND: We examined the relationship between 10-year predicted atherosclerosis cardiovascular disease (ASCVD) risk score and 25-hydroxyvitamin D in Koreans aged 40-79 years. METHODS: A population-based, cross-sectional design was used from data based on the Korea National Health and Nutrition Examination Survey 2014. RESULTS: A total of 1,134 healthy Koreans aged 40-79 years were included. A positive relationship between serum 25-hydroxyvitamin D level and ASCVD score was shown in women (ß=0.015) after adjusting for central obesity, physical activity, and supplement intake. The chances of being in the moderate to high risk (risk group, ASCVD score ≥5%) with vitamin D sufficiency (serum 25-hydroxyvitamin D ≥20 ng/mL) was 1.267-fold (95% confidence interval, 1.039-1.595) greater than the chance of being included in the group with vitamin D deficiency (serum 25-hydroxyvitamin D <20 ng/mL) after adjustments in women. CONCLUSION: Our research indicated a significantly positive association between 25-hydroxyvitamin D and ASCVD score. Further detailed studies to evaluate this correlation are needed.

Chronic exercise improves repeated restraint stress-induced anxiety and depression through 5HT1A receptor and cAMP signaling in hippocampus.

PURPOSE: Mood disorders such as anxiety and depression are prevalent psychiatric illness, but the role of 5HT1A in the anti-depressive effects of exercise has been rarely known yet. We investigated whether long-term exercise affected a depressive-like behavior and a hippocampal 5HT1A receptor-mediated cAMP/PKA/CREB signaling in depression mice model. METHODS: To induce depressive behaviors, mice were subjected to 14 consecutive days of restraint stress (2 hours/day). Depression-like behaviors were measured by forced swimming test (TST), and anxiety-like behavior was assessed by elevated plus maze (EPM). Treadmill exercise was performed with 19 m/min for 60 min/day, 5 days/week from weeks 0 to 8. Restraint stress was started at week 6 week and ended at week 8. To elucidate the role of 5HT1A in depression, the immunoreactivities of 5HT1A were detected in hippocampus using immunohistochemical technique. RESULTS: Chronic/repeated restraint stress induced behavioral anxiety and depression, such as reduced time and entries in open arms in EPM and enhanced immobility time in FST. These anxiety and depressive behaviors were ameliorated by chronic exercise. Also, these behavioral changes were concurrent with the deficit of 5HT1A and cAMP/PKA/CREB cascade in hippocampus, which was coped with chronic exercise. CONCLUSION: These results suggest that chronic exercise may improve the disturbance of hippocampal 5HT1A-regulated cAMP/PKA/CREB signaling in a depressed brain, thereby exerting an antidepressive action.

Maternal exercise during pregnancy affects mitochondrial enzymatic activity and biogenesis in offspring brain.

The present study addresses whether exercise during pregnancy in mouse alters mitochondrial function in the brains of the resultant offspring. We divided pregnant mice into four groups: a control group and groups of mice that exercised for 20 (E20m), 30 (E30m) and 40 min/d (E40m). The pregnant mice ran on a treadmill at 12 m/min, 5 d/week for a duration of 3 weeks. The protein expression of cytochrome c oxidase subunit Va (CVa) was downregulated in the offspring of the E20m group, unlike that in the control animals, whereas CVa expression was reserved in the E40m neonates. The F1-ATPase catalytic core (Core) protein expression levels were the highest in the E40m group neonates. Complex I, IV and ATPase activities were significantly lower in the E20m group than that in the control group neonates and were reserved in the E30m and E40m group neonates. The activities of citrate synthase and pyruvate dehydrogenase were consistent with those of complex I, IV and ATPase. Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha, mitochondrial transcription factor A, nuclear respiratory factor-1 and mitochondrial DNA showed high levels of expression in the E40m neonates compared with the other groups. Malondialdehyde (MDA) levels in E40m neonates were higher than that in the controls but were lower than that in the E20m neonates. Finally, 40 min/d of maternal exercise improved mitochondrial function in the resultant pups and was concomitant with brain-derived trophic factor induction in the hippocampus, thereby functionally improving short-term memory.

The effect of exercise in cool, control and hot environments on cardioprotective HSP70 induction.

A number of environmental and metabolic stimuli rapidly induce the expression of several highly conserved proteins such as heat shock proteins (HSPs) or stress proteins. The purpose of this study was to investigate the effects of a single bout of submaximal exercise in varying ambient temperatures on cardiac and skeletal muscle. Adult male Sprague-Dawley rats were randomly placed in one of three ambient temperature groups; control (23 degrees C), hot (41 degrees C) and cool (11 degrees C). Each exercise bout consisted of treadmill running at 17 m/min and 0% grade. Tissue HSP70 levels for all groups were determined using analysis of variance in two factorial design (2 x 3). Baseline rectal temperature was similar for all three groups. In the control and hot temperature groups, final rectal temperatures differed from the baseline values (p<.05). The rectal temperature from the control/exercise group were 38.5+/-0.3 degrees C at rest and 39.8+/-0.3 degrees C at exhaustion, the hot/exercise group were 38.4+/-0.3 degrees C at rest and 41.2+/-0.9 degrees C at exhaustion and the cool/exercise group were 38.2+/-0.3 degrees C at rest and 38.5+/-0.2 degrees C at exhaustion. The running time was 102.0+/-39.5 min at the control/exercise group, 44.1+/-18.0 min at the hot/exercise group, and 55.4+/-11.9 min at the cool/exercise group. The level of soleus, cardiac and extensor digitorium longus (EDL) HSP70 in cool temperature does not change during a single bout of submaximal exercise. Whereas a single bout of submaximal exercise in hot and control ambient temperatures increases HSP70 accumulation in locomotor muscles, such as the soleus and cardiac, but not in the EDL tissue. This study shows that the changes of HSP70 level induced by a single bout of submaximal exercise at various ambient temperatures (control, hot and cool) depend on the rectal temperature.