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Running exercise effectively ameliorates depressive symptoms in humans and depression-like behaviors in animals, but the underlying mechanisms remain unclear. Microglia-mediated neuroinflammation plays a major role in the development of depression. The medial prefrontal cortex (mPFC) is a key brain region involved in depression and is sensitive to physical activity. Whether the antidepressant effect of running exercise involves changes in mPFC microglia is not understood. The animals were subjected to chronic unpredictable stress (CUS) intervention followed by treadmill running. The sucrose preference test and elevated plus maze test or tail suspension test were used for behavioral assessment of the animals. The number of microglia in the mPFC was quantified by immunohistochemistry and stereology. The density and morphology of microglia were analyzed via immunofluorescence staining combined with three-dimensional laser scanning techniques. The mRNA expressions of inflammatory cytokines in the mPFC were examined via quantitative real-time PCR. Running exercise effectively alleviated depressive-like behaviors in depression model animals. Running exercise reversed the increase in the number of microglia and the density of activated microglia in the mPFC of CUS animals. Running exercise effectively reversed the changes in microglia (reduced cell body area, total branch length and branch complexity) in the mPFC of CUS animals. Furthermore, running exercise regulated the gene expressions of pro−/antiinflammatory cytokines in the mPFC of CUS animals. Our results suggested that the antidepressant effects of running exercise may involve decreasing the number of activated microglia, reversing morphological changes in microglia in the mPFC, and reducing inflammatory responses. • Running exercise can alleviate depressive-like symptoms in CUS model animals. • This study provides complete evidence of microglial activation within the mPFC of CUS model animals. • Running exercise can reverse microglial activation within the mPFC of CUS model animals. • Running exercise reverses the changes in the gene expressions of inflammatory cytokines in the mPFC of CUS model animals. • The therapeutic effect of running exercise on depression may be mediated by microglia in the mPFC. [ABSTRACT FROM AUTHOR]

A review of the 5,000 m race training protocols was conducted to facilitate the search and comparison between the existing protocols. This study aimed to systematically review the literature on the physical training protocols applied to athletes and well-trained runners who have investigated the impacts on performance in 5,000 m races and/or recognised performance parameters in this distance. This review was carried out following PRISMA guidelines. The search used PubMed, Web of Science and Scopus electronic databases. The PICOS strategy was used to define eligibility criteria. A total of 35 studies were included in the systematic review; 25 were selected for qualitative analysis from the databases, and 10 articles were identified while reading the articles selected by the main search. Selected studies had their methodological quality and risk of bias assessed by the Cochrane Risk of Bias Tool. Interval running protocols are the main potentiators for performance in the 5,000 m. Among all running protocols that improved the 5,000 m time trial or any of the predicted variables studied in this review, 33.33% used both interval and continuous training, 33.33% used uphill HIIT, and 13.33% used HIIT. Neuromuscular protocols showed effects mainly on running economy. Eight of the eleven neuromuscular intervention protocols showed improvement in this variable. Among all neuromuscular protocols that improved the 5,000 m time trial or any of the predicted variables studied in this review, 50% applied complex training, 25% used plyometric as an intervention and 25% used strength resistance training. The coach must choose the combination of the studied protocols in order to guarantee performance improvement. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of running exercise on depression-like behaviors in chronic unpredictable stress (CUS)-induced depression mice and GABAergic interneurons, PV+ interneurons and ratio of GAD67+/PV+ cells in medial prefrontal cortex (mPFC). Methods After mouse model of depression was successfully established through CUS, these male C57BL/6 mice aged 4~6 weeks were randomly divided into control group, CUS control group and CUS+running group according to the results of sucrose preference test. The behaviors of the 3 groups were evaluated with sucrose preference test, forced swimming test and tail suspension test. The mRNA expression levels of GAD1, GAD2, PV and CCK in mPFC of mice were detected using qRT-PCR. The number of GABAergic interneurons and PV+ interneurons in mPFC of mice were quantified using immunohistochemical assay and unbiased stereological technique, and the ratio of PV+/GAD67+ cells was calculated. Results Compared with those in CUS control group, the mice from the CUS+running and control groups showed a significantly higher percentage of sucrose preference (P0.05). The mRNA level of PV, number of PV+ interneurons and ratio of PV+/GAD67+ cells in mPFC were remarkably lower in the CUS group than the CUS +running group and control group (P

Abstract Background The role of physical exercise in the prevention of Alzheimer’s disease (AD) has been widely studied. Microglia play an important role in AD. Triggering receptor expressed in myeloid cells 2 (TREM2) is expressed on microglia and is known to mediate microglial metabolic activity and brain glucose metabolism. However, the relationship between brain glucose metabolism and microglial metabolic activity during running exercise in APP/PS1 mice remains unclear. Methods Ten-month-old male APP/PS1 mice and wild-type mice were randomly divided into sedentary groups or running groups (AD_Sed, WT_Sed, AD_Run and WT_Run, n = 20/group). Running mice had free access to a running wheel for 3 months. Behavioral tests, [18]F-FDG-PET and hippocampal RNA-Seq were performed. The expression levels of microglial glucose transporter (GLUT5), TREM2, soluble TREM2 (sTREM2), TYRO protein tyrosine kinase binding protein (TYROBP), secreted phosphoprotein 1 (SPP1), and phosphorylated spleen tyrosine kinase (p-SYK) were estimated by western blot or ELISA. Immunohistochemistry, stereological methods and immunofluorescence were used to investigate the morphology, proliferation and activity of microglia. Results Long-term voluntary running significantly improved cognitive function in APP/PS1 mice. Although there were few differentially expressed genes (DEGs), gene set enrichment analysis (GSEA) showed enriched glycometabolic pathways in APP/PS1 running mice. Running exercise increased FDG uptake in the hippocampus of APP/PS1 mice, as well as the protein expression of GLUT5, TREM2, SPP1 and p-SYK. The level of sTREM2 decreased in the plasma of APP/PS1 running mice. The number of microglia, the length and endpoints of microglial processes, and the ratio of GLUT5+/IBA1+ microglia were increased in the dentate gyrus (DG) of APP/PS1 running mice. Running exercise did not alter the number of 5-bromo-2′-deoxyuridine (BrdU)+/IBA1+ microglia but reduced the immunoactivity of CD68 in the hippocampus of APP/PS1 mice. Conclusions Running exercise inhibited TREM2 shedding and maintained TREM2 protein levels, which were accompanied by the promotion of brain glucose metabolism, microglial glucose metabolism and morphological plasticity in the hippocampus of AD mice. Microglia might be a structural target responsible for the benefits of running exercise in AD. Promoting microglial glucose metabolism and morphological plasticity modulated by TREM2 might be a novel strategy for AD treatment.

Depression is one of the most common mental illnesses and seriously affects all aspects of life. Running exercise has been suggested to prevent or alleviate the occurrence and development of depression; however, the underlying mechanisms of these effects remain unclear. Independent studies have indicated that astrocytes play essential roles and that the medial prefrontal cortex (mPFC) is an important brain region involved in the pathology underlying depression. However, it is unknown whether running exercise achieves antidepressant effects by affecting the number of astrocytes and glutamate transport function in the mPFC. Here, animal models of depression were established using chronic unpredictable stress (CUS), and depression‐like behavior was assessed by the sucrose preference test. After successfully establishing the depression model, experimental animals performed running exercise. Glial fibrillary acidic protein‐positive (GFAP+) cell number in the mPFC was precisely quantified using immunohistochemical and stereological methods, and the densities of bromodeoxyuridine‐positive (BrdU+) and BrdU+/GFAP+ cells in the mPFC were measured using a semiquantitative immunofluorescence assay. Changes in glutamate transporter gene expression in mPFC astrocytes were detected by mRNA sequencing and qRT–PCR. We found that running exercise reversed CUS‐induced decreases in sucrose preference, increased astrocyte number and the density of newborn astrocytes, and reversed decreases in gene expression levels of GFAP, S100b, and the glutamate transporters GLT‐1 and GLAST in the mPFC of CUS animals. These results suggested that changes in astrocyte number and glutamate transporter function may be potential meditators of the effects of running exercise in the treatment of depression. [ABSTRACT FROM AUTHOR]

The current study has been designed to explore the effects of running exercise training protocols (ETPs), with different intensities, on testicular redox and antioxidant capacities. Moreover, the crosstalk between oxidative stress (OS) and mitochondria‐related apoptosis was analysed. To this end, 24 Wistar rats were subdivided into sedentary control, low‐ (LICT), moderate‐ (MICT), and high (HICT)‐intensity continuous running ETP groups. Following 8 weeks, the Johnsen score, sperm count, testicular malondialdehyde (MDA) content, total oxidant status (TOS), and redox biomarkers, including glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) levels were evaluated. Additionally, the expression levels of Bcl‐2, Bax, caspase‐3, proteins involving in the mitochondria‐related apoptosis, and the apoptotic index were analysed. The LICT and MICT running ETPs did not affect the spermatogenesis development, sperm count, and antioxidant and redox capacities. Accordingly, no significant changes were revealed in Bcl‐2, Bax, and caspase‐3 expression levels and apoptosis index compared to sedentary rats. In contrast, the HICT‐induced rats showed a significant (p < 0.05) reduction in spermatogenesis development, sperm count, antioxidant and redox capacities versus control, LICT, and MICT groups. Moreover, the expression of Bcl‐2 was decreased, while the Bax and caspase‐3 expression levels were increased in the HICT‐induced group. Finally, the apoptosis index was increased in the HICT group. In conclusion, the suppressed redox system after HICT can trigger the mitochondria‐mediated ROS overload, result in OS condition in the testicular tissue, and reversely target the mitochondrial membrane permeability. All of these molecular alterations are suspected to initiate progressive mitochondria‐related apoptosis after HICT. [ABSTRACT FROM AUTHOR]

Introduction: Exercise becomes a stress when performed at an intensity above the lactate threshold (LT) because at that point the plasma adrenocorticotropic hormone (ACTH), a marker of stress response, increases. It is possible that the exercise-induced ACTH response is regulated at least by arginine vasopressin (AVP) and possibly by corticotropin-releasing hormone (CRH), but this remains unclear. To clarify the involvement of these factors, it is useful to intervene pharmacologically in the regulatory mechanisms, with a physiologically acceptable exercise model. Methods: We used a special stress model of treadmill running (aerobic exercise) for male Wistar rats, which mimic the human physiological response, where plasma ACTH levels increase at just above the LT for 30 min. Animals were administered the AVP V1b receptor antagonist SSR149415 (SSR) and/or the CRH type 1 receptor antagonist CP154526 (CP) intraperitoneally before the exercise, which allowed the monitoring of exercise-induced ACTH response. Immunohistochemical evaluation of activated AVP and CRH neurons with exercise was performed for the animals' hypothalami. Results: A single injection of either antagonist, SSR or CP, resulted in inhibited ACTH levels after exercise stress. Moreover, the combined injection of SSR and CP strongly suppressed ACTH secretion during treadmill running to a greater extent than each alone. The running-exercise-induced activation of both AVP and CRH neurons in the hypothalamus was also confirmed. Conclusion: These results lead us to hypothesize that AVP and CRH are cooperatively involved in exercise-induced ACTH response just above the LT. This may also reflect the stress response with moderate-intensity exercise in humans. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the effect of purslane supplementation on oxidative stress, inflammation and muscle damage biomarkers after completing high-intensity interval exercise (HIIE). Methods: Nine healthy female runners completed a HIIE treadmill protocol comprising 1 min at 100% of the peak treadmill velocity attained in a preliminary exhaustive incremental treadmill test, interspersed by 1 min of passive recovery, until they had run for 2.5 km. Athletes repeated this test following 10 days of supplementation with 1000 mg per day of purslane. Results: At baseline (i.e., absence of purslane supplementation) the HIIE protocol increased 9-HODE (p < 0.001), 13-HODE (p < 0.001), IL-17 (p < 0.001), TNF-α (p < 0.001), and LDH (p < 0.001). After purslane consumption, resting 9-HODE, 13-HODE, IL-17, TNF-α, and LDH were lowered (p < 0.001) and IL-10 was increased (p < 0.001) compared to before purslane supplementation. After purslane consumption and following the HIIE protocol, the responses of these biomarkers were lower compared to baseline (p < 0.001). Conclusion: Ten days of purslane supplementation blunted the perturbation to biomarkers of oxidative stress, inflammation and muscle damage in female runners completing a HIIE protocol.

The medial prefrontal cortex (mPFC) is thought to be closely associated with emotional processes, decision making, and memory. Previous studies have identified the prefrontal cortex as one of the most vulnerable brain regions in Alzheimer's disease (AD). Running exercise has widely been recognized as a simple and effective method of physical activity that enhances brain function and slows the progression of AD. However, the effect of exercise on the mPFC of AD is unclear. To address these issues, we investigated the effects of 4 months of exercise on the numbers of spinophilin‐immunoreactive puncta and neurons in the mPFC of 12‐month‐old APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice using stereological methods. The spatial learning and memory abilities of mice were tested using the Morris water maze. Four months of running exercise delayed declines in spatial learning and memory abilities. The stereological results showed significantly lower numbers of spinophilin‐immunoreactive puncta and neurons in the mPFC of APP/PS1 mice than in the wild‐type control group. The numbers of spinophilin‐immunoreactive puncta and neurons in the mPFC of running APP/PS1 mice were significantly greater than those in the APP/PS1 control mice. In addition, running‐induced improvements in spatial learning and memory were significantly associated with running‐induced increases in spinophilin‐immunoreactive puncta and neurons numbers in the mPFC. Running exercise could delay the loss of spinophilin‐immunoreactive puncta and neurons in the mPFC of APP/PS1 mice. This finding might provide an important structural basis for exercise‐induced improvements in the spatial learning and memory abilities of individuals with AD. [ABSTRACT FROM AUTHOR]

Background: The role of physical exercise in the prevention of Alzheimer's disease (AD) has been widely studied. Microglia play an important role in AD. Triggering receptor expressed in myeloid cells 2 (TREM2) is expressed on microglia and is known to mediate microglial metabolic activity and brain glucose metabolism. However, the relationship between brain glucose metabolism and microglial metabolic activity during running exercise in APP/PS1 mice remains unclear.Methods: Ten-month-old male APP/PS1 mice and wild-type mice were randomly divided into sedentary groups or running groups (AD_Sed, WT_Sed, AD_Run and WT_Run, n = 20/group). Running mice had free access to a running wheel for 3 months. Behavioral tests, [18]F-FDG-PET and hippocampal RNA-Seq were performed. The expression levels of microglial glucose transporter (GLUT5), TREM2, soluble TREM2 (sTREM2), TYRO protein tyrosine kinase binding protein (TYROBP), secreted phosphoprotein 1 (SPP1), and phosphorylated spleen tyrosine kinase (p-SYK) were estimated by western blot or ELISA. Immunohistochemistry, stereological methods and immunofluorescence were used to investigate the morphology, proliferation and activity of microglia.Results: Long-term voluntary running significantly improved cognitive function in APP/PS1 mice. Although there were few differentially expressed genes (DEGs), gene set enrichment analysis (GSEA) showed enriched glycometabolic pathways in APP/PS1 running mice. Running exercise increased FDG uptake in the hippocampus of APP/PS1 mice, as well as the protein expression of GLUT5, TREM2, SPP1 and p-SYK. The level of sTREM2 decreased in the plasma of APP/PS1 running mice. The number of microglia, the length and endpoints of microglial processes, and the ratio of GLUT5+/IBA1+ microglia were increased in the dentate gyrus (DG) of APP/PS1 running mice. Running exercise did not alter the number of 5-bromo-2'-deoxyuridine (BrdU)+/IBA1+ microglia but reduced the immunoactivity of CD68 in the hippocampus of APP/PS1 mice.Conclusions: Running exercise inhibited TREM2 shedding and maintained TREM2 protein levels, which were accompanied by the promotion of brain glucose metabolism, microglial glucose metabolism and morphological plasticity in the hippocampus of AD mice. Microglia might be a structural target responsible for the benefits of running exercise in AD. Promoting microglial glucose metabolism and morphological plasticity modulated by TREM2 might be a novel strategy for AD treatment. [ABSTRACT FROM AUTHOR]

Background. A game of chess represents a legitimate physical and psychological stress due to its strategic and cognitively demanding nature over a long period of time. This very challenging situation has not been thoroughly explored and, to the best of our knowledge, there is no research report that has concentrated on both heart rate variability and energy expenditure for deeper understanding of chess players' performance. The main aim of the present study was to examine the HRV and EE of chess players before, during and after a competition, as well as the moderate level of running exercise. Methods. The sample comprised 24 (19 men, 5 women; Mage=24.8) volunteer chess players who have been playing chess regularly for at least 5 years. The average National Chess Rating (NCR) of participants was determined as 1526. In addition, a total of ten participants have International Chess Rating (ELO) rating (mean = 1588). We obtained participants' body mass indexes before the experiment took place. Participants' HR and HRV were taken through the chess competition, and running exercises took place in 3 different time periods; before (15 min), during (30 min) and after (15 min). Results. Our results indicated that there was a significant difference on HRV between chess competition and running exercises HRV (RMSSD, SDNN, NN50 and RR) (p=.001). Besides, there was a significant difference on participants' EE between a chess competition and a moderate level of running (p=.001). Conclusions. HRV values determined in chess competition and running exercise are different from each other. Contradictory to our speculative hypothesis, the current results provide that a moderate level of running exercises requires more energy expenditure than a chess game. [ABSTRACT FROM AUTHOR]

• Moderate, intermittent voluntary exercise improved cognitive function in a model of GWI. • Moderate, intermittent voluntary exercise improved mood function in a model of GWI. • Intermittent voluntary exercise transformed activated microglia into noninflammatory microglia. • Intermittent voluntary exercise reduced astrocyte hypertrophy. • Intermittent voluntary exercise enhanced hippocampal neurogenesis. Persistent cognitive and mood impairments in Gulf War Illness (GWI) are associated with chronic neuroinflammation, typified by hypertrophied astrocytes, activated microglia, and increased proinflammatory mediators in the brain. Using a rat model, we investigated whether a simple lifestyle change such as moderate voluntary physical exercise would improve cognitive and mood function in GWI. Because veterans with GWI exhibit fatigue and post-exertional malaise, we employed an intermittent voluntary running exercise (RE) regimen, which prevented exercise-induced stress. The GWI rats were provided access to running wheels three days per week for 13 weeks, commencing ten weeks after the exposure to GWI-related chemicals and stress (GWI-RE group). Groups of age-matched sedentary GWI rats (GWI-SED group) and naïve rats were maintained parallelly. Interrogation of rats with behavioral tests after the 13-week RE regimen revealed improved hippocampus-dependent object location memory and pattern separation function and reduced anxiety-like behavior in the GWI-RE group compared to the GWI-SED group. Moreover, 13 weeks of RE in GWI rats significantly reversed activated microglia with short and less ramified processes into non-inflammatory/antiinflammatory microglia with highly ramified processes and reduced the hypertrophy of astrocytes. Moreover, the production of new neurons in the hippocampus was enhanced when examined eight weeks after the commencement of RE. Notably, increased neurogenesis continued even after the cessation of RE. Collectively, the results suggest that even a moderate, intermittent physical exercise has the promise to improve brain function in veterans with GWI in association with suppression of neuroinflammation and enhancement of hippocampal neurogenesis. [ABSTRACT FROM AUTHOR]

The intersection of asymptotes method is used to describe the changes in skin temperature of the human body during running exercise. Skin temperature variations are induced by thermoregulatory mechanisms, which are influenced by both physiological and environmental factors. The aim of this study is to succinctly and comprehensively connect these factors to create an easily interpretable tool for understanding this process. Based on simplified energy balance equations under dynamic conditions for both the early and late stages of exercise, two asymptotic solutions for skin temperature are derived. The point of intersection between these solutions determines the moment at which the transition from skin vasoconstriction to vasodilation occurs. The shapes and the intersection of the two asymptotes enable the inference and interpretation of actual skin temperature variations throughout the course of exercise. [ABSTRACT FROM AUTHOR]

In this research, mice were gavaged with different doses of lemon seed flavonoids (LSF) for 4 weeks, and vitamin C was used as a positive control to investigate its effects on anti-fatigue and antioxidant capacity in exhaustively exercised mice. The results obtained from the study indicated that both vitamin C and LSF could significantly increase the running exhaustion time of mice, and the exhaustion time of mice was prolonged with increasing LSF concentration. LSF can increase hepatic glycogen and the free fatty acid content and reduce the lactate and urea nitrogen contents in a dose-dependent manner in mice. Serum CK, AST, and ALT levels in mice decreased gradually with increasing LSF concentration. LSF increased SOD and CAT levels and decreased MDA levels in mice in a dose-dependent manner. LSF could also enhance nNOS, eNOS, and ASCT1 mRNA expression and decrease syncytin-1, iNOS and TNF-α expression in the skeletal muscle of mice. By HPLC analysis, LSF was found to contain epigallocatechin, caffeic acid, epicatechin, vitexin, quercetin, and hesperidin, which are common flavonoids of this species. Thus, it was observed that LSF has good anti-fatigue and antioxidant capacities, and its anti-fatigue effect is related to improving the hepatic glycogen reserve capacity, increasing fat mobilization, and reducing lactate accumulation and protein decomposition. The antioxidant capacity of LSF is related to scavenging free radicals and reducing lipid peroxidation, and its antioxidant effect comes from its five antioxidant flavonoids. In conclusion, LSF has high development and application prospects in nutritional supplements. Practical applications: Lemon seed is the waste of lemon processing, which contains abundant flavonoids. The flavonoids in lemon seed can be used to exert its antioxidant effect and recover from exhausted exercise. Therefore, it can be concluded that lemon seed flavonoids are functional components that can be used as exercise recovery substances. [ABSTRACT FROM AUTHOR]

Physical activity has been correlated with a reduced risk of cognitive decline, including that associated with vascular dementia, mild cognitive impairment (MCI) and Alzheimer's disease (AD); recent literature suggests this may in part result from benefits to the cerebrovascular network. Using a transgenic (Tg) mouse model of AD, we evaluated the effect of running on cortical and hippocampal vascular morphology, cerebral amyloid angiopathy, amyloid plaque load, and spatial memory. TgCRND8 mice present with progressive amyloid pathology, advancing from the cortex to the hippocampus in a time-dependent manner. We postulated that the characteristic progression of pathology could lead to differential, time-dependent effects of physical activity on vascular morphology in these brain regions at 6 months of age. We used two-photon fluorescent microscopy and 3D vessel tracking to characterize vascular and amyloid pathology in sedentary TgCRND8 mice compared those who have a history of physical activity (unlimited access to a running wheel, from 3 to 6 months of age). In sedentary TgCRND8 mice, capillary density was found to be lower in the cortex and higher in the hippocampus compared to non-transgenic (nonTg) littermates. Capillary length, vessel branching, and non-capillary vessel tortuosity were also higher in the hippocampus of sedentary TgCRND8 compared to nonTg mice. Three months of voluntary running resulted in normalizing cortical and hippocampal microvascular morphology, with no significant difference between TgCRND8 and nonTg mice. The benefits of physical activity on cortical and hippocampal vasculature in 6-month old TgCRND8 mice were not paralleled by significant changes on parenchymal and cerebral amyloid pathology. Short-term spatial memory— as evaluated by performance in the Y-maze— was significantly improved in running compared to sedentary TgCRND8 mice. These results suggest that long-term voluntary running contributes to the maintenance of vascular morphology and spatial memory in TgCRND8 mice, even in the absence of an effect on amyloid pathology.

Background: The aim of this study was to determine the effect of purslane supplementation on oxidative stress, inflammation and muscle damage biomarkers after completing high-intensity interval exercise (HIIE). Material and methods: Nine healthy female runners completed a HIIE treadmill protocol comprising 1 min at 100% of the peak treadmill velocity attained in a preliminary exhaustive incremental treadmill test, interspersed by 1 min of passive recovery, until they had run for 2.5 km. Athletes repeated this test following 10 days of supplementation with 1000 mg per day of purslane. Results: At baseline (i.e., absence of purslane supplementation) the HIIE protocol increased 9-HODE (p < 0.001), 13-HODE (p < 0.001), IL-17 (p < 0.001), TNF-α (p < 0.001), and LDH (p < 0.001). After purslane consumption, resting 9-HODE, 13-HODE, IL-17, TNF-α, and LDH were lowered (p < 0.001) and IL-10 was increased (p < 0.001) compared to before purslane supplementation. After purslane consumption and following the HIIE protocol, the responses of these biomarkers were lower compared to baseline (p < 0.001). Conclusions: Ten days of purslane supplementation blunted the perturbation to biomarkers of oxidative stress, inflammation and muscle damage in female runners completing a HIIE protocol. [ABSTRACT FROM AUTHOR]

Exercise has been argued to improve cognitive function in both humans and rodents. Angiogenesis significantly contributes to brain health, including cognition. The hippocampus is a crucial brain region for cognitive function. However, studies quantifying the capillary changes in the hippocampus after running exercise are lacking. Moreover, the molecular details underlying the effects of running exercise remain poorly understood. We show that endogenous nitric oxide contributes to the beneficial effects of running exercise on cognition and hippocampal capillaries. Four weeks of running exercise significantly improved spatial memory ability and increased the number of capillaries in the cornu ammonis 1 subfield and dentate gyrus of Sprague-Dawley rats. Running exercise also significantly increased nitric oxide synthase activity and nitric oxide content in the rat hippocampus. After blocking the synthesis of endogenous nitric oxide by lateral ventricular injection of NG-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase inhibitor, the protective effect of running exercise on spatial memory was eliminated. The protective effect of running exercise on angiogenesis in the cornu ammonis 1 subfield and dentate gyrus of rats was also absent after nitric oxide synthase inhibition. Therefore, during running excise, endogenous nitric oxide may contribute to regulating spatial memory ability and angiogenesis in cornu ammonis 1 subfield and dentate gyrus of the hippocampus. [ABSTRACT FROM AUTHOR]

Running speed affects theta (6–10 Hz) oscillations, the most prominent rhythm in the rat hippocampus. Many reports have found a strong positive correlation between locomotion speed and the amplitude and frequency of theta oscillations. However, less is known about how other rhythms such as delta (0.5–4 Hz) and gamma (25–100 Hz) are affected, and how consecutive runs impact oscillatory activity in hippocampal networks. Here, we investigated whether the successive execution of short-term runs modulates local field potentials (LFPs) in the rat hippocampus. To do this, we trained Long-Evans rats to perform voluntary 15-s runs at 30 cm/s on a treadmill placed on the central stem of an eight-shape maze, in which they subsequently performed a spatial alternation task. We bilaterally recorded CA1 LFPs while rats executed at least 35 runs on the treadmill-maze apparatus. Within running periods, we observed progressive increases in delta band power along with decreases in the power of the theta and gamma bands across runs. Concurrently, the inter-hemispheric phase coherence in the delta band significantly increased, while in the theta and gamma bands exhibited no changes. Delta power and inter-hemispheric coherence correlated better with the trial number than with the actual running speed. We observed no significant differences in running speed, head direction, nor in spatial occupancy across runs. Our results thus show that consecutive treadmill runs at the same speed positively modulates the power and coherence of delta oscillations in the rat hippocampus. [ABSTRACT FROM AUTHOR]

Although the antidepressant effects of running exercise have been widely reported, further research is still needed to determine the structural bases for these effects. Astrocyte processes physically contact many synapses and directly regulate the numbers of synapses, but it remains unclear whether running exercise can modulate astrocyte morphological complexity and astrocyte-contacted synapses in the hippocampus of the mice with depressive-like behavior. Male C57BL/6 J mice underwent four weeks of running exercise after four weeks of chronic unpredictable stress (CUS). The sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were used to assess anhedonia in mice. Western blotting was used to measure the expression of astrocyte- and synapse-related proteins. Immunofluorescence and 3D reconstruction were used to quantify the density and morphology of astrocytes, and astrocyte-contacted synapses in each hippocampal subregion. Four weeks of running exercise alleviated depressive-like symptoms in mice. The expression of astrocyte- and synapse-related proteins in the hippocampus; astrocyte process lengths, process numbers, and dendritic arborization; and the number of astrocyte-contacted PSD95 positive synapses in the CA2–3 and DG regions were significantly decreased in the mice with depressive-like behavior, and running exercise successfully reserved these changes. Running exercise improved the decreases in astrocyte morphological complexity and astrocyte-contacted PSD95 positive synapses in the CA2–3 and DG regions of the mice with depressive-like behavior, suggesting that the physical interactions between astrocytes and synapses can be increased by running exercise, which might be an important structural basis for the antidepressant effects of running exercise. • Running exercise increased the expression of astrocyte- and synapse-related proteins in the hippocampus of depressed mice. • Running exercise improved astrocyte morphological complexity in the CA2–3 and DG regions of depressed mice. • Running exercise increased the number of astrocyte-contacted synapses in the CA2–3 and DG regions of depressed mice. [ABSTRACT FROM AUTHOR]

The understanding that fluid ingestion attenuates thermoregulatory and circulatory stress during exercise in the heat was based on studies conducted in relatively dry (∼50% RH) environments. It remains undetermined whether similar effects occur during exercise in a warm and more humid environment, where evaporative capacity is reduced. Nine well-trained, unacclimatised male runners were randomly assigned to perform four experimental trials where they ran for 60 min at an intensity of 70% VO2max followed by an incremental exercise test until volitional exhaustion. The four trials consisted of non-fluid ingestion (NF) and fluid ingestion (FI) in a warm-dry (WD) and warm-humid condition (WH). Time to exhaustion (TTE), body temperature (Tb), whole body sweat rate, partitional calorimetry measures, heart rate and plasma volume were recorded during exercise. There was no significant difference in Tb following 60 min of exercise in FI and NF trial within both WD (37.3°C ± 0.4 vs. 37.4°C ± 0.3; p > 0.05) and WH conditions (38.0°C ± 0.4 vs. 38.1°C ± 0.4; p > 0.05). The TTE was similar between FI and NF trials in both WH and WD, whereas exercise capacity was significantly shorter in WH than WD (9.1 ± 2.8 min vs. 12.7 ± 2.4 min, respectively; p = 0.01). Fluid ingestion failed to provide any ergogenic benefit in attenuating thermoregulatory and circulatory stress during exercise in the WH and WD conditions. Consequently, exercise performance was not enhanced with fluid ingestion in the warm-humid condition, although the humid environment detrimentally affected exercise endurance.

Introduction: Any stimulus that causes a biological response is called stress. Regular exercise has positive effects on the brain. Exercise improves anxiety in people by affecting the hypothalamic-pituitary-adrenal axis and reducing glucocorticoids. Enriched environment (EE) as a non-drug solution has positive effects on cognitive behaviors and also increases the ability to cope with anxiety, fear, and stress. In this research, we decided to investigate the simultaneous effect of exercise and environmental enrichment on anxiety-like behaviors of healthy male rats. Methods and Materials: A total of 32 male Wistar rats were divided into four treatment groups: control, enriched environment (EE), exercise (EX), and EE+EX. Animals in EE groups housed in large cages (50×50×50 cm) were exposed to objects of different toys and objects for 3 weeks. EX animals were forced to run on a treadmill once a day for 3 consecutive weeks. Open field and elevated plus maze tests were used to evaluate anxiety. Results: EX and EE animals separately did not show significant performance in reducing anxiety compared to the control group. When animals were treated with EE and EX simultaneously, they showed significant performance in reducing anxiety compared to control, EX, or EE groups separately. The reduction of anxiety in the EE+EX group was significantly higher than in the control group, EX, and EE alone. Conclusions: Exercise and environmental enrichment individually did not have a significant effect on reducing the animals' anxiety, but the combination of the two significantly reduced the animals' anxiety. These results may have clinical implications for behavioral interventions in conditions with anxiety symptoms. [ABSTRACT FROM AUTHOR]

Purpose: Blood rheology is a key determinant of blood flow and tissue perfusion. There are still large discrepancies regarding the effects of an acute running exercise on blood rheological properties and red blood cell (RBC) physiology. We investigated the effect of a 10 km running trial on markers of blood rheology and RBC physiology in endurance trained athletes.Methods: Blood was sampled before and after the exercise to measure lactate and glucose, hematological and hemorheological parameters (blood viscosity, RBC deformability, and aggregation), eryptosis markers (phosphatidylserine and CD47 exposure, RBC reactive oxygen species), RBC-derived microparticles (RBC-MPs), and RBC electrophysiological activity. Weight was measured before and after exercise. Peripheral oxygen saturation and heart rate were monitored before and during the trial.Results: Blood lactate and glucose levels increased after exercise and subjects significantly lost weight. All athletes experienced a significant fall in oxygen saturation. Mean corpuscular volume (MCV) was increased from 95.1 ± 3.2 to 96.0 ± 3.3 and mean corpuscular hemoglobin concentration (MCHC) decreased after exercise suggesting a slight RBC rehydration. Exercise increased RBC deformability from 0.344 ± 0.04 to 0.378 ± 0.07, decreased RBC aggregates strength and blood viscosity, while hematocrit (Hct) remained unaffected. While RBC electrophysiological recording suggested a modulation in RBC calcium content and/or chloride conductance, eryptosis markers and RBC-MPs were not modified by the exercise.Conclusion: A 10 km acute running exercise had no effect on RBC senescence and membrane blebbing. In contrast, this exercise increased RBC deformability, probably through rehydration process which resulted in a decrease in blood viscosity. [ABSTRACT FROM AUTHOR]

Exercise is important to maintain skeletal muscle mass through stimulation of protein synthesis, which is a major ATP-consuming process for cells. However, muscle cells have to face high energy demand during contraction. The present study aimed to investigate protein synthesis regulation during aerobic exercise in mouse hindlimb muscles. Male C57Bl/6J mice ran at 12 m/min for 45 min or at 12 m/min for the first 25 min followed by a progressive increase in velocity up to 20 m/min for the last 20 min. Animals were injected intraperitoneally with 40 nmol/g of body weight of puromycin and euthanized by cervical dislocation immediately after exercise cessation. Analysis of gastrocnemius, plantaris, quadriceps, soleus, and tibialis anterior muscles revealed a decrease in protein translation assessed by puromycin incorporation, without significant differences among muscles or running intensities. The reduction of protein synthesis was associated with a marked inhibition of mammalian target of rapamycin complex 1 (mTORC1)-dependent phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1, a mechanism consistent with reduced translation initiation. A slight activation of AMP-activated protein kinase consecutive to the running session was measured but did not correlate with mTORC1 inhibition. More importantly, exercise resulted in a strong upregulation of regulated in development and DNA damage 1 (REDD1) protein and gene expressions, whereas transcriptional regulation of other recognized exercise-induced genes (IL-6, kruppel-like factor 15, and regulator of calcineurin 1) did not change. Consistently with the recently discovered role of REDD1 on mitochondria-associated membranes, we observed a decrease in mitochondria-endoplasmic reticulum interaction following exercise. Collectively, these data raise questions concerning the role of mitochondria-associated endoplasmic reticulum membrane disruption in the regulation of muscle proteostasis during exercise and, more generally, in cell adaptation to metabolic stress. NEW & NOTEWORTHY How muscles regulate protein synthesis to cope with the energy demand during contraction is poorly documented. Moreover, it is unknown whether protein translation is differentially affected among mouse hindlimb muscles under different physiological exercise modalities. We showed here that 45 min of running decreases puromycin incorporation similarly in 5 different mouse muscles. This decrease was associated with a strong increase in regulated in development and DNA damage 1 protein expression and a significant disruption of the mitochondria and sarcoplasmic reticulum interaction. [ABSTRACT FROM AUTHOR]

The understanding that fluid ingestion attenuates thermoregulatory and circulatory stress during exercise in the heat was based on studies conducted in relatively dry (∼50% RH) environments. It remains undetermined whether similar effects occur during exercise in a warm and more humid environment, where evaporative capacity is reduced. Nine well-trained, unacclimatised male runners were randomly assigned to perform four experimental trials where they ran for 60 min at an intensity of 70% VO2max followed by an incremental exercise test until volitional exhaustion. The four trials consisted of non-fluid ingestion (NF) and fluid ingestion (FI) in a warm-dry (WD) and warm-humid condition (WH). Time to exhaustion (TTE), body temperature (Tb), whole body sweat rate, partitional calorimetry measures, heart rate and plasma volume were recorded during exercise. There was no significant difference in Tb following 60 min of exercise in FI and NF trial within both WD (37.3°C ± 0.4 vs. 37.4°C ± 0.3; p > 0.05) and WH conditions (38.0°C ± 0.4 vs. 38.1°C ± 0.4; p > 0.05). The TTE was similar between FI and NF trials in both WH and WD, whereas exercise capacity was significantly shorter in WH than WD (9.1 ± 2.8 min vs. 12.7 ± 2.4 min, respectively; p = 0.01). Fluid ingestion failed to provide any ergogenic benefit in attenuating thermoregulatory and circulatory stress during exercise in the WH and WD conditions. Consequently, exercise performance was not enhanced with fluid ingestion in the warm-humid condition, although the humid environment detrimentally affected exercise endurance. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the impact of running exercise training protocols (ETPs) with varying intensities on inflammatory responses, with a specific focus on the interactions between inflammatory mediators, cytokines, and Leydig cell steroidogenic activity, as well as testosterone secretion. To this end, 24 Wistar rats were subdivided into sedentary control, low (LICT), moderate (MICT), and high (HICT) intensity continuous running ETP groups. After 8 weeks, the expression levels of Toll-like receptor-4 (TLR-4), nuclear factor-kappa-B (NF-KB), interleukin-6 (IL-6), interleukin-10 (IL-10), Tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and the testicular nitric oxide (NO) content were assessed and compared between groups. Moreover, the mean distributions of Leydig cells/mm2 of interstitial connective tissue, their steroidogenic activity, and serum level of testosterone were assessed. The LICT did not show any significant (p > 0.05) change in the expression levels of all aforementioned biomarkers. In contrast, both the MICT and HICT groups demonstrated a significant (p < 0.05) increase in the expression levels of TLR-4, NFK-B, IL-6, TNF-α, iNOS, and COX-2 at both the mRNA and protein levels. The testicular NO has increased in HICT and MICT groups. Despite a decrease in the distribution of Leydig cells in both the MICT and HICT groups, the HICT group exhibited a significant (p < 0.05) reduction in Leydig cell steroidogenic activity and serum testosterone levels. In conclusion, our findings revealed that ETPs can influence Leydig cell steroidogenic activity and testosterone secretion, contingent on their intensity. These effects are attributed to alterations in the expression levels of pro-inflammatory mediators and cytokines. • MICT and HICT led to a significant increase in testicular TLR-4 and NFK-B expression at the mRNA level. • MICT and HICT resulted in an upregulation of testicular IL-6, IL-10, and TNF-α expression. • LICT, MICT, and HICT significantly increased the testicular mRNA level of TNF-α. • MICT and HICT groups displayed a remarkable increase in testicular NO level. • MICT and HICT groups exhibited a remarkable increase in testicular NO level. • MICT and HICT increased TLR-4 expression. • MICT group exhibited compensatory steroidogenic activity • HICT reduced the proportion of Leydig cells with positive steroidogenic activity. • HICT decreased serum testosterone level. [ABSTRACT FROM AUTHOR]

Abstrak Ketahanan berolahraga menunjang latihan fisik yang optimal untuk meningkatkan derajat kesehatan dan kebugaran jasmani. Penurunan kapasitas ketahanan olahraga disebabkan oleh dehidrasi dan penurunan karbohidrat dalam otot selama melakukan latihan. Air kelapa berpotensi sebagai minuman olahraga karena memiliki derajat keasaman yang rendah, gula seimbang, kandungan mineral, dan bersifat isotonis. Penelitian ini bertujuan mengetahui efek konsumsi air kelapa terhadap ketahanan dan kebugaran berolahraga diukur dari jarak tempuh dan VO2max selama latihan lari. Penelitian dilakukan di Lapangan FPOK UPI Bandung periode Juli 2015–Februari 2016. Bahan penelitian yang digunakan adalah air kelapa dalam kemasan. Air mineral, air gula 5%, dan minuman olahraga isotonik yang digunakan sebagai pembanding. Subjek penelitian adalah 120 orang laki-laki, berusia 18–23 tahun yang dibagi menjadi 4 kelompok untuk tiap-tiap bahan uji. Setelah pemanasan, subjek berlari secepatnya selama 30 menit. Bahan uji diberikan sebelum dan setiap 10 menit selama lari. Jarak yang ditempuh dicatat dalam satuan meter. Analisis dengan one-way ANOVA yang dilanjutkan dengan uji least significant difference (LSD) dengan α

The purpose of this study was to investigate the effects of β-alanine supplementation on a 10 km running time trial and lactate concentration in physically active adults. Sixteen healthy subjects were divided randomly into two groups: β-alanine (n = 8) and placebo group (n = 8). The experimental group ingested 5 g/day of β-alanine plus 1 g of resistant starch, and control group ingested 6 g of resistant starch, both for 23 days. Time to complete a 10-km running time trial and lactate concentration following the test were assessed at baseline and post 23 days. The running training program was performed three times per week on non-consecutive days (day 1: running 7 km; day 2: six sprints of 500 m at maximum speed with 2 min of recovery; day 3: running 12 km). The time to complete a 10-km running time trial decreased significantly only for the β-alanine group (Pre = 3441 ± 326.7, Post = 3209 ± 270.5 s, p < 0.05). When analyzing the delta (Time post minus Time at baseline value) there was a statistically significant difference between the β-alanine vs placebo group (-168.8 ± 156.6 vs. -53.60 ± 78.81 s, p = 0.007), respectively. In addition, the β-alanine group presented lower blood lactate concentration after the 10-km test (β-alanine: Pre = 8.45 ± 1.94 vs. Post = 6.95 ± 2.44 mmol/L; Placebo: Pre = 8.7 ± 3.0 vs. Post = 10.8 ± 2.5 mmol/L, p = 0.03). In conclusion, β-alanine supplementation improved the 10-km running time trial and reduced lactate concentration in physically active adults.

Previous studies have suggested that changes in the white matter might play an important role in the pathogenic processes of Alzheimer's disease (AD). However, no study has investigated sex differences in these changes. Previous studies found that running exercise could delay both the decline in spatial learning and memory abilities as well as the changes in the white matter during early AD in male mice. However, whether exercise also has an effect on the changes in the white matter in female AD mice remains unknown. To address these questions, 6- and 10-month-old male and female APP/PS1 double transgenic AD mice were used. The 6-month-old male and female APP/PS1 double transgenic AD mice underwent a 4-month running exercise regime. The white matter volume and parameters of the myelinated fibers in the white matter of the 10-month-old exercised and non-exercised male and female AD mice were investigated using electron microscopy and stereological methods. There were no significant differences in the mean escape latencies between the male and female AD mice in the non-exercised groups, but after 4 months of treadmill exercise, the mean escape latencies of the female exercised AD mice had significantly shortened compared with those of the male exercised AD mice. The total white matter volume and most of the parameters of the myelinated fibers of the white matter in the female AD mice were significantly lower than those of the male AD mice. The total length of the myelinated fibers with diameters ranging from 0.6 to 0.7 μm, the axonal diameter of the myelinated fibers and the g-ratio of the myelinated fibers in the white matter of the exercised female AD mice were significantly increased compared with those of the non-exercised female AD mice. There were sex-specific differences in the white matter and myelinated fibers of white matter in the AD mice. Running exercise more effectively delayed the decline in spatial learning and memory abilities and delayed the changes in the myelinated fibers of the white matter in female transgenic mice with early AD than in male transgenic mice.

Previous studies have suggested that changes in the white matter might play an important role in the pathogenic processes of Alzheimer's disease (AD). However, no study has investigated sex differences in these changes. Previous studies found that running exercise could delay both the decline in spatial learning and memory abilities as well as the changes in the white matter during early AD in male mice. However, whether exercise also has an effect on the changes in the white matter in female AD mice remains unknown. To address these questions, 6- and 10-month-old male and female APP/PS1 double transgenic AD mice were used. The 6-month-old male and female APP/PS1 double transgenic AD mice underwent a 4-month running exercise regime. The white matter volume and parameters of the myelinated fibers in the white matter of the 10-month-old exercised and non-exercised male and female AD mice were investigated using electron microscopy and stereological methods. There were no significant differences in the mean escape latencies between the male and female AD mice in the non-exercised groups, but after 4 months of treadmill exercise, the mean escape latencies of the female exercised AD mice had significantly shortened compared with those of the male exercised AD mice. The total white matter volume and most of the parameters of the myelinated fibers of the white matter in the female AD mice were significantly lower than those of the male AD mice. The total length of the myelinated fibers with diameters ranging from 0.6 to 0.7 μm, the axonal diameter of the myelinated fibers and the g-ratio of the myelinated fibers in the white matter of the exercised female AD mice were significantly increased compared with those of the non-exercised female AD mice. There were sex-specific differences in the white matter and myelinated fibers of white matter in the AD mice. Running exercise more effectively delayed the decline in spatial learning and memory abilities and delayed the changes in the myelinated fibers of the white matter in female transgenic mice with early AD than in male transgenic mice. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effects of β-alanine supplementation on a 10 km running time trial and lactate concentration in physically active adults. Sixteen healthy subjects were divided randomly into two groups: β-alanine (n = 8) and placebo group (n = 8). The experimental group ingested 5 g/day of β-alanine plus 1 g of resistant starch, and control group ingested 6 g of resistant starch, both for 23 days. Time to complete a 10-km running time trial and lactate concentration following the test were assessed at baseline and post 23 days. The running training program was performed three times per week on non-consecutive days (day 1: running 7 km; day 2: six sprints of 500 m at maximum speed with 2 min of recovery; day 3: running 12 km). The time to complete a 10-km running time trial decreased significantly only for the β-alanine group (Pre = 3441 ± 326.7, Post = 3209 ± 270.5 s, p < 0.05). When analyzing the delta (Time post minus Time at baseline value) there was a statistically significant difference between the β-alanine vs placebo group (-168.8 ± 156.6 vs. -53.60 ± 78.81 s, p = 0.007), respectively. In addition, the β-alanine group presented lower blood lactate concentration after the 10-km test (β-alanine: Pre = 8.45 ± 1.94 vs. Post = 6.95 ± 2.44 mmol/L; Placebo: Pre = 8.7 ± 3.0 vs. Post = 10.8 ± 2.5 mmol/L, p = 0.03). In conclusion, β-alanine supplementation improved the 10-km running time trial and reduced lactate concentration in physically active adults. [ABSTRACT FROM AUTHOR]

To investigate the effect of running exercise on the number of the neurons in the hippocampus of young APP/PS1 mice, twenty 6-month-old male APP/ PS1 transgenic mice were randomly divided into the APP/PS1 control (AD control) group and the APP/PS1 running (AD running) group (10 mice per group), and ten wild-type mice of the littermate were regarded as the wild-type (WT) group. The AD running mice ran on motorized treadmill machiene for 4 months, while the WT mice and AD control mice were housed in standard condition without running. Then, Morris water maze tests (MWM) were used to assess the special learning and memory abilities of mice in three groups. The stereological methods were used to quantitatively evaluate the volume of the hippocampus, CA1/2, CA3 and the dentate gyrus (DG) and count the number of the neurons in CA1/2, CA3 and DG. We found that 4-month running effectively shortened the escape latency of young APP/PS1 control mice in MWM. More importantly, 4-month running effectively increased the volumes of the hippocampus, CA1/2, CA3 and DG and increased the number of neurons in CA1/2, CA3 and DG in young APP/PS1 mice. The present results suggested that 4-month running has significant beneficial effects on the spatial learning and memory capacities of young APP/PS1 mice and could delay the progress of atrophy of hippocampus and the neuron death in CA1/2, CA3 and DG in young APP/PS1 mice. [ABSTRACT FROM AUTHOR]

Reloading of atrophied muscles after hindlimb suspension unloading (HSU) can induce injury and prolong recovery. Low-impact exercise, such as voluntary wheel running, has been identified as a nondamaging rehabilitation therapy in rodents, but its effects on muscle function, morphology, and satellite cell activity after HSU are unclear. This study tested the hypothesis that low-impact wheel running would increase satellite cell proliferation and improve recovery of muscle structure and function after HSU in mice. Young adult male and female C57BL/6 mice ( n = 6/group) were randomly placed into five groups. These included HSU without recovery (HSU), normal ambulatory recovery for 14 days after HSU (HSU+NoWR), and voluntary wheel running recovery for 14 days after HSU (HSU+WR). Two control groups were used: nonsuspended mouse cage controls (Control) and voluntary wheel running controls (ControlWR). Satellite cell activation was evaluated by providing mice 5-bromo-2'-deoxyuridine (BrdU) in their drinking water. As expected, HSU significantly reduced in vivo maximal force, decreased in vivo fatigability, and decreased type I and IIa myosin heavy chain (MHC) abundance in plantarflexor muscles. HSU+WR mice significantly improved plantarflexor fatigue resistance, increased type I and IIa MHC abundance, increased fiber cross-sectional area, and increased the percentage of type I and IIA muscle fibers in the gastrocnemius muscle. HSU+WR mice also had a significantly greater percentage of BrdU-positive and Pax 7-positive nuclei inside muscle fibers and a greater MyoD-to-Pax 7 protein ratio compared with HSU+NoWR mice. The mechanotransduction protein Yes-associated protein (YAP) was elevated with reloading after HSU, but HSU+WR mice had lower levels of the inactive phosphorylated YAPserine127, which may have contributed to increased satellite cell activation with reloading after HSU. These results indicate that voluntary wheel running increased YAP signaling and satellite cell activity after HSU and this was associated with improved recovery. NEW & NOTEWORTHY Although satellite cell involvement in muscle remodeling has been challenged, the data in this study suggest that voluntary wheel running increased satellite cell activity and suppressed Yes-associated protein (YAP) protein relative to no wheel running and this was associated with improved muscle recovery of force, fatigue resistance, expression of type I myosin heavy chain, and greater fiber cross-sectional area after disuse. [ABSTRACT FROM AUTHOR]

The risk of cognitive decline during Alzheimer's disease (AD) can be reduced if physical activity is maintained; however, the specific neural events underlying this beneficial effect are still uncertain. To quantitatively investigate the neural events underlying the effect of running exercise on middle-aged AD subjects, 12-month-old male APP/PS1 mice were randomly assigned to a control group or running group, and age-matched non-transgenic littermates were used as a wild-type group. AD running group mice were subjected to a treadmill running protocol (regular and moderate intensity) for four months. Spatial learning and memory abilities were assessed using the Morris water maze. Hippocampal amyloid plaques were observed using Thioflavin S staining and immunohistochemistry. Hippocampal volume, number of neurons, and number of newborn cells (BrdU+ cells) in the hippocampus were estimated using stereological techniques, and newborn neurons were observed using double-labelling immunofluorescence. Marked neuronal loss in both the CA1 field and dentate gyrus (DG) and deficits in both the neurogenesis and survival of new neurons in the DG of middle-aged APP/PS1 mice were observed. Running exercise could improve the spatial learning and memory abilities, reduce amyloid plaques in the hippocampi, delay neuronal loss, induce neurogenesis, and promote the survival of newborn neurons in the DG of middle-aged APP/PS1 mice. Exercise-induced protection of neurons and adult neurogenesis within the DG might be part of the important structural basis of the improved spatial learning and memory abilities observed in AD mice. [ABSTRACT FROM AUTHOR]

Neurogenesis might influence oligodendrogenesis and selectively instruct myelination in the mammalian brain. Running exercise could induce neurogenesis and protect the myelin sheaths in the dentate gyrus of AD mice. It is unclear whether running exercise can protect myelin sheaths in the absence of neurogenesis in the hippocampus of AD mice. Six-month-old male APP/PS1 transgenic mice were randomly assigned to a control group (Tg control) or a running group (Tg runner), and age-matched non-transgenic littermates were used as a wild-type group (WT control). The Tg runner mice were subjected to a running protocol for four months. The behaviors of the mice in the three groups were then assessed using the Morris water maze, and related quantitative parameters of the myelin sheaths within the CA1 field were investigated using unbiased stereological and electron microscopy techniques. Learning and spatial memory performance, CA1 volume, the volumes of the myelinated fibers, and myelin sheaths in the CA1 field were all significantly worse in the Tg control mice than in the WT control mice. Learning and spatial memory performance, CA1 volume and the volume of the myelin sheaths in the CA1 field were all significantly greater in the Tg runner mice than in the Tg control mice. These results reveal demyelinating lesions in the CA1 field of Alzheimer’s disease (AD) mice and indicate that running exercise could protect against myelin sheath degeneration in the absence of neurogenesis, thereby reducing CA1 atrophy and delaying the onset and progression of AD. [ABSTRACT FROM AUTHOR]

The antidepressive effects of exercise have been a focus of research and are hypothesized to remodel the brain networks constructed by myelinated fibers. However, whether the antidepressant effects of exercise are dependent on changes in white matter myelination are unknown. Therefore, we chose chronic unpredictable stress (CUS) as a model of depression and designed an experiment. After a 4-week CUS period, 40 animals were tested using the sucrose preference test (SPT) and the open field test (OFT). The depressed rats then underwent 4-week running exercise. Next, electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. After the 4-week CUS stimulation, body weight, sucrose preference and scores on the OFT were significantly lower in the depression rats than in the unstressed rats ( p < .05). After undergoing a 4-week running exercise, the depression rats showed a significantly greater sucrose preference than the depression control rats without running exercise ( p < .05). Furthermore, the white matter parameters of the depression rats (including the white matter volumes, the length and volumes of myelinated fibers, and the volumes and thickness of the myelin sheaths) were significantly reduced after the CUS period ( p < .05). However, these white matter parameters were significantly increased after running exercise ( p < .05). The present study is the first to provide evidence that running exercise has positive effects on white matter and the myelinated fibers of white matter in depressed rats, and this evidence might provide an important theoretical basis for the exercise-mediated treatment of depression. [ABSTRACT FROM AUTHOR]

To investigate clothing-induced differences in human thermal response and running performance, eight male athletes participated in a repeated-measure study by wearing three sets of clothing (CloA, CloB, and CloC). CloA and CloB were body-mapping-designed with 11% and 7% increased capacity of heat dissipation respectively than CloC, the commonly used running clothing. The experiments were conducted by using steady-state running followed by an all-out performance running in a controlled hot environment. Participants’ thermal responses such as core temperature (Tc), mean skin temperature (), heat storage (S), and the performance running time were measured. CloA resulted in shorter performance time than CloC (323.1 ± 10.4 s vs. 353.6 ± 13.2 s,p = 0.01), and induced the lowest, smallest ΔTc, and smallestSin the resting and running phases. This study indicated that clothing made with different heat dissipation capacities affects athlete thermal responses and running performance in a hot environment. Practitioner Summary:A protocol that simulated the real situation in running competitions was used to investigate the effects of body-mapping-designed clothing on athletes’ thermal responses and running performance. The findings confirmed the effects of optimised clothing with body-mapping design and advanced fabrics, and ensured the practical advantage of developed clothing on exercise performance. [ABSTRACT FROM AUTHOR]

Responsiveness to physiological stimuli, such as exercise and muscular inactivation, differs in individuals. However, the mechanisms responsible for these individual differences remain poorly understood. We tested whether a prior experience of exercise training affects the responses of skeletal muscles to unloading. Young rats were assigned to perform daily running training with a treadmill for 8 wk. After an additional 8 wk of normal habitation, the rats were hindlimb unloaded by tail suspension for 1 wk. Fast-twitch plantaris, gastrocnemius, and tibialis anterior muscles did not atrophy after unloading in rats with training experience, although soleus muscle lost weight similar to sedentary rats. We also analyzed the transcriptome in plantaris muscle with RNA sequencing followed by hierarchical clustering analysis and found that a subset of genes that were generally upregulated in sedentary rats after unloading were less responsive in rats with training experience. The distribution of histone 3 was diminished at the loci of these genes during the training period. Although the deposition of histone 3 was restored after an additional period of normal habitation, the incorporation of H3.3 variant was promoted in rats with training experience. This remodeling of nucleosomes closely correlated to the conformational changes of chromatin and suppressed gene expression in response to unloading. These results suggest that exercise training stimulated the early turnover of histone components, which may alter the responsiveness of gene transcription to physiological stimuli. NEW & NOTEWORTHY The present study demonstrates that disuse atrophy was suppressed in fast-twitch skeletal muscles of rats with training experience in early life. We also found a subset of genes that were less responsive to unloading in the muscle of rats with training experience. It was further determined that exercise training caused an early turnover of nucleosome components, which may alter the responsiveness of genes to stimulus in later life. [ABSTRACT FROM AUTHOR]

Background: Gestational infections induced inflammation (GIII) is a cause of various postnatal neurological deficits in developing countries. Such intra uterine insults could result in persistent learning-memory disabilities. There are no studies elucidating the efficacy of adolescence exercise on spatial learning- memory abilities of young adult rats pre-exposed to inflammatory insult during fetal life. Aims and Objectives: The present study addresses the efficacy of physical (running) exercise during adolescent period in attenuating spatial memory deficits induced by exposure to GIII in rats. Materials and Methods: Pregnant Wistar dams were randomly divided into control and lipopolysaccharide (LPS) groups, injected intra peritoneally (i.p) with saline (0.5ml) or lipopolysaccharide (LPS) (0.5mg/kg) on alternate days from gestation day 14 (GD 14) till delivery. After parturition, pups were divided into 3 groups (n=6/group) a) Sham control and LPS group divided into 2 subgroups- b) LPS and c) LPS exercise group. Running exercise was given only to LPS exercise group during postnatal days (PNDs) 30 to 60 (15min/day). Spatial learning and memory performance was assessed by Morris water maze test (MWM), on postnatal day 61 to 67 in all groups. Results: Young rats pre-exposed to GIII and subjected to running exercise through juvenile period displayed significant decrease in latency to reach escape platform and spent significant duration in target quadrant in MWM test, compared to age matched LPS group. Results of the current study demonstrated that exercise through juvenile/adolescent period effectively mitigates gestational inflammation-induced cognitive deficits in young adult rats. Conclusion: Inflammation during gestation impairs offspring’s spatial memory and learning abilities. Whereas, early postnatal physical exercise attenuates, to higher extent, cognitive impairment resulted from exposure to LPS induced inflammation during intrauterine growth period.

Introduction: The present study was conducted to directly compare the efficacy of running exercise and telmisartan treatment on angiotensin (Ang) II-mediated atherosclerosis and plaque vulnerability.Materials and Methods: Apolipoprotein E-deficient (ApoE-/-) mice with Ang II-mediated atherosclerosis (2-kidney, 1-clip [2K1C] renovascular hypertension model) were randomized into 3 groups: treadmill running exercise (RUN), telmisartan treatment (TEL), and sedentary untreated controls (SED) for 5 weeks. Atherosclerosis was assessed using histological and immunohistochemical analyses. Gene expression was determined by real-time reverse transcription polymerase chain reaction.Results: TEL but not RUN mice significantly decreased (50%) atherosclerotic lesion size compared to SED. RUN and TEL promoted plaque stabilization to a similar degree in ApoE-/- 2K1C mice. However, plaque composition and vascular inflammatory markers were differently affected: RUN decreased plaque macrophage infiltration (35%), whereas TEL reduced lipid core size (88%); RUN significantly increased aortic peroxisome proliferator-activated receptor (PPAR)-α, -δ, and -γ expression, whereas TEL significantly modulated T-helper 1/T-helper 2 (Th1/Th2) aortic response toward an anti-inflammatory state (decreased aortic interleukin [IL] 2 to IL-10 and IL-2 to IL-13 expression ratios). Plaque smooth muscle cell content was similarly increased (128% and 141%, respectively). Aortic AT1 and AT2 receptor expression as well as aortic CD11c/CD206 and IL-1β/IL-1ra expression ratios were not significantly modulated by either RUN or TEL.Conclusion: Running exercise and telmisartan treatment are equally effective in preventing Ang II-mediated plaque vulnerability but through distinct cellular and molecular mechanisms. Our findings further support the use of exercise training and selective AT1 receptor blocker therapies for atherosclerotic cardiovascular disease prevention. [ABSTRACT FROM AUTHOR]

Running has been shown to improve depressive symptoms when used as an adjunct to medication. However, the mechanisms underlying the antidepressant effects of running are not fully understood. Changes of capillaries in white matter have been discovered in clinical patients and depression model rats. Considering the important part of white matter in depression, running may cause capillary structural changes in white matter. Chronic unpredictable stress (CUS) rats were provided with a 4-week running exercise (from the fifth week to the eighth week) for 20 minutes each day for 5 consecutive days each week. Anhedonia was measured by a behavior test. Furthermore, capillary changes were investigated in the control group, the CUS/Standard group, and the CUS/Running group using stereological methods. The 4-week running increased sucrose consumption significantly in the CUS/Running group and had significant effects on the total volume, total length, and total surface area of the capillaries in the white matter of depression rats. These results demonstrated that exercise-induced protection of the capillaries in white matter might be one of the structural bases for the exercise-induced treatment of depression. It might provide important parameters for further study of the vascular mechanisms of depression and a new research direction for the development of clinical antidepressant means. J. Comp. Neurol. 524:3577-3586, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Running exercise (RE) improves cognition, formation of anterograde memories, and mood, alongside enhancing hippocampal neurogenesis. Aprevious investigation in a mouse model showed that RE-induced increased neurogenesis erases retrograde memory (Akers et al., 2014). However, it is unknown whether RE-induced forgetting is common to all species. We ascertained whether voluntary REinduced enhanced neurogenesis interferes with the recall of spatial memory in rats. Young rats assigned to either sedentary (SED) or running exercise (RE) groups were first subjected to eight learning sessions in a water maze. A probe test (PT) conducted 24 h after the final training session confirmed that animals in either group had a similar ability for the recall of short-term memory. Following this, rats in the RE group were housed in larger cages fitted with running wheels, whereas rats in the SED group remained in standard cages. Animals in the RE group ran an average of 78kmin 4 weeks. A second PT performed 4 weeks after the first PT revealed comparable ability for memory recall between animals in the RE and SED groups, which was evidenced through multiple measures of memory retrieval function. The RE group displayed a 1.5- to 2.1-fold higher hippocampal neurogenesis than SED rats. Additionally, both moderate and brisk RE did not interfere with the recall of memory, although increasing amounts of RE proportionally enhanced neurogenesis. In conclusion, RE does not impair memory recall ability in a rat model despite substantially increasing neurogenesis. [ABSTRACT FROM AUTHOR]

The molecular mechanisms by which exercise improves brain function and capillaries in the cerebral cortex are unclear. Exercise can increase the expression of nitric oxide (NO) in the brain, and endogenous NO is thought to exert beneficial effects on proangiogenic factors, antiangiogenic factors and brain function. Therefore, we hypothesized that running exercise might improve brain function and enhance angiogenesis through endogenous NO. The following three groups of rats were administered intracerebroventricular (i.c.v.) injections before running exercise each day for 4 weeks: exercise+ L -NAME group (i.c.v. L -NAME, an NO synthase blocker, dose: 1 μmol/μl and 5 μl/day; treadmill exercise, 20 min/day), exercise group (i.c.v. normal saline, 5 μl/day; treadmill exercise, 20 min/day), and sham group (i.c.v. normal saline, 5 μl/day; no treadmill exercise). Subsequently, the spatial learning and memory abilities were tested using a Morris water maze, and the nitric oxide synthase (NOS) activity in the cerebral cortex in each group of rats was measured using a method involving nitric acid reductase and metabolic chemistry. The parameters of the cortical capillaries were quantitatively investigated using an immunohistochemistry technique and stereological methods. The expression levels of proangiogenic factors (VEGF and FGF-2) and an antiangiogenic inhibitor (endostatin) in the cerebral cortex were tested using a Western blot analysis. Running exercise significantly improved the rats' spatial learning and memory abilities and increased NOS activity in the cortex. Running exercise also subsequently improved the expression of proangiogenic factors (VEGF and FGF-2) and the length, volume and surface area of capillaries and reduced the expression of antiangiogenic factors (endostatin) in the cortex. In contrast, the L -NAME treatment attenuated the effects of running exercise. Running exercise regulates proangiogenic factors, antiangiogenic factors and angiogenesis in the cerebral cortex via a partially NO-dependent mechanism, and influencing endogenous NO might potentially affect the exercise-related beneficial effects on cognitive ability and cortical capillaries. [ABSTRACT FROM AUTHOR]

[Display omitted] • 3D-kinematic analysis determined fine gait and joint movements of hindlimbs in mice. • Unilateral brain damage (BD) affected the gait and trajectory of ankles in both limbs. • BD with exercise mice improved movements without compensatory operation. Motor dysfunction, such as gait impairment, is a major disability induced by traumatic brain injury or stroke. Treadmill running is often used as a physical exercise (Ex) clinically and experimentally for the recovery of patients. In animal experiments, although dynamic behavioral deficits can be evaluated using scoring systems, local and minor behaviors are difficult to determine. This study aims to evaluate motor dysfunction and recovery after brain damage (BD) with/without mild-intensity running Ex in mice using three-dimensional (3D) kinematic analysis. To determine exercise intensity, C57/BL6-strain male young adult mice were examined in an incremental running test while the pulmonary gas exchange of O 2 and CO 2 were measured. The animals were then subjected to left hemidecortication as BD, and some mice performed Ex (10 m/min for 30 min 5 times/wk) for 4 weeks. The BD with Ex and BD or sham-operated mice (sham) without (w/o) Ex had their gait recorded by four synchronized cameras, and gait was evaluated via 3D-kinematic analysis. The BD w/o Ex mice significantly differed in stride, step, and stride width for both limbs compared to the sham w/o Ex mice. The BD with Ex mice showed improvement. The BD w/o Ex mice had restricted ankle movements and impairment in dorsal/planter flexing using trajectory analysis. Consistent with these impairments, the nonaffected side also exhibited a different trajectory, suggesting compensatory movements. These results suggest that the appropriate Ex after BD recovered motor function. Furthermore, the present study suggested that 3D-kinematic analysis is a powerful tool for detecting minor behavioral alterations owing to the impairment of the affected side and the compensation of the unaffected side. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of a combination of running and food restriction on the chemical properties of the bone in young female rats using Raman spectroscopy. Furthermore, we investigated whether the chemical property parameters correlated with the bone-breaking strength., Methods: Female Sprague-Dawley rats (7 weeks old) were randomly divided into four groups: sedentary and ad libitum feeding (SED, n = 8), voluntary running exercise and ad libitum feeding (EX, n = 8), sedentary and 30% food-restricted (SED-FR, n = 8), and voluntary running exercise and 30% food-restricted (EXFR, n = 8). The experiment was conducted for a period of 12 weeks. Four parameters measured by Raman spectroscopy were used to evaluate the bone chemical quality., Results: Exercise and restriction had significant interactions on the mineral to matrix ratio. The mineral- to-matrix ratio in the SED-FR group was significantly higher than that in the SED group and significantly lower in the EX-FR group than that in the SED-FR group. Running exercise had significant effects on increasing the crystallinity and carbonate-to-phosphate ratio. In the ad libitum intake condition, there were significant positive correlations between breaking energy and crystallinity (r = 0.593) and between breaking energy and carbonate-to-phosphate ratio (r = 0.854)., Conclusion: Our findings show that running exercise and food restriction, alone or in combination, affect the chemical properties of bone. Furthermore, under ad libitum intake conditions, positive correlations were found between the breaking energy and crystallinity, or carbonate-to-phosphate ratio.

Rehabilitative approaches benefit motor functional recovery after stroke and relate to neuronal plasticity. We investigated the effects of a treadmill running exercise on the motor functional recovery and neuronal plasticity after collagenase-induced striatal intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with type IV collagenase into the left striatum to induce ICH. Sham-operated animals were injected with saline instead of collagenase. The animals were randomly assigned to the sham control (SC), the sham exercise (SE), the ICH control (IC), or the ICH exercise (IE) group. The exercise groups were forced to run on a treadmill at a speed of 9 m/min for 30 min/day between days 4 and 14 after surgery. Behavioral tests were performed using a motor deficit score, a beam-walking test and a cylinder test. At fifteen days after surgery, the animals were sacrificed, and their brains were removed. The motor function of the IE group significantly improved compared with the motor function of the IC group. No significant differences in cortical thickness were found between the groups. The IC group had fewer branches and shorter dendrite lengths compared with the sham groups. However, dendritic branches and lengths were not significantly different between the IE and the other groups. Tropomyosin-related kinase B (TrkB) expression levels increased in the IE compared with IC group, but no significant differences in other protein (brain-derived neurotrophic factor, BDNF; Nogo-A; Rho-A/Rho-associated protein kinase 2, ROCK2) expression levels were found between the groups. These results suggest that improved motor function after a treadmill running exercise after ICH may be related to the prevention of dendritic regression due to TrkB upregulation. [ABSTRACT FROM AUTHOR]