The potential role of creatine supplementation in neurodegenerative diseases.

PURPOSE: The maintenance of energy balance in the body, especially in energy-demanding tissues like the muscles and the central nervous system, depends on creatine (Cr). In addition to improving muscle function, Cr is necessary for the bioenergetics of the central nervous system because it replenishes adenosine triphosphate without needing oxygen. Furthermore, Cr possesses anti-oxidant, anti-apoptotic, and anti-excitotoxic properties. Clinical research on neurodegenerative illnesses has shown that Cr supplementation results in less effective outcomes. With a brief update on the possible role of Cr in human, animal, and in vitro experiments, this review seeks to offer insights into the ideal dosage regimen. METHODS: Using specified search phrases, such as "creatine and neurological disorder," "creatine supplementation and neurodegenerative disorders," and "creatine and brain," we searched articles in the PubMed database and Google Scholar. We investigated the association between creatine supplementation and neurodegenerative illnesses by examining references. RESULTS: The neuroprotective effects of Cr were observed in in vitro and animal models of certain neurodegenerative diseases, while clinical trials failed to reproduce favorable outcomes. CONCLUSION: Determining the optimal creatinine regime for increasing brain creatinine levels is essential for maintaining brain health and treating neurodegeneration.

Lactate consumption mediates repeated high-intensity interval exercise-enhanced executive function in adult males.

PURPOSE: Lactate is a principal energy substrate for the brain during exercise. A single bout of high-intensity interval exercise (HIIE) can increase the blood lactate level, brain lactate uptake, and executive function (EF). However, repeated HIIE can attenuate exercise-induced increases in lactate level and EF. The lactate levels in the brain and blood are reported to be correlated with exercise-enhanced EF. However, research is yet to explain the cause-and-effect relationship between lactate and EF. This study examined whether lactate consumption improves the attenuated exerciseenhanced EF caused by repeated HIIE. METHODS: Eleven healthy men performed two sets of HIIE, and after each set, 30 min were given for rest and examination. In the 2nd set, the subjects consumed experimental beverages containing (n = 6) and not containing (n = 5) lactate. Blood, cardiovascular, and psychological variables were measured, and EF was evaluated by the computerized color-word Stroop test. RESULTS: The lactate group had a higher EF (P < 0.05) and tended to have a higher blood lactate level (P = 0.082) than the control group in the 2nd set of HIIE. Moreover, blood lactate concentration was correlated with the interference score (i.e., reverse score of EF) (r = -0.394; P < 0.05). CONCLUSION: Our results suggest that the attenuated exercise-enhanced EF after repeated HIIE can be improved through lactate consumption. However, the role of lactate needs to be elucidated in future studies, as it can be used for improving athletes' performance and also in cognitive decline-related clinical studies.

Effects of Different Light Sources on Neural Activity of the Paraventricular Nucleus in the Hypothalamus.

Background and Objectives: Physical function is influenced by light irradiation, and interest in the influence of light irradiation on health is high. Light signals are transmitted from the retina to the suprachiasmatic nucleus (SCN) via the retinal hypothalamic tract as non-image vision. Additionally, the SCN projects a nerve to the paraventricular nucleus (PVN) which acts as a stress center. This study examined the influences of three different light sources on neural activity in the PVN region using two different color temperatures. Materials and Methods: Experiments were conducted using twenty-eight Institute of Cancer Research (ICR) mice (10 week old males). Three light sources were used: (1) organic light-emitting diode (OLED) lighting, (2) LED lighting, and (3) fluorescent lighting. We examined the effects of light irradiation from the three light sources using two different color temperatures (2800 K and 4000 K). Perfusion was done 60 min after light irradiation, and then the brain was removed from the mouse for an immunohistochemistry analysis. c-Fos was immunohistochemically visualized as a marker of neural activity in the PVN region. Results: The number of c-Fos-positive cells was found to be significantly lower under OLED lighting and LED lighting conditions than under fluorescent lighting at a color temperature of 2800 K, and significantly lower under OLED lighting than LED lighting conditions at a color temperature of 4000 K. Conclusions: This study reveals that different light sources and color temperatures alter the neural activity of the PVN region. These results suggest that differences in the light source or color temperature may affect the stress response.

Exercise Prevents Memory Consolidation Defects Via Enhancing Prolactin Responsiveness of CA1 Neurons in Mice Under Chronic Stress.

We investigated the effects of regular exercise on chronic stress-induced memory consolidation impairment and its underlying mechanism. We focused on prolactin (PRL)-modulated calcium-permeable (CP)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) in neurons in the CA1 stratum lacunosum-moleculare (SLM) area of the dorsal hippocampus. Regular exercise protected against memory retention defects and prevented dendritic retraction in apical distal segments of hippocampal CA1 neurons, as indicated by enhanced dendritic ramification, dendritic length, spine density, and synaptic protein levels following chronic stress. Regular exercise normalized synaptic CP-AMPAR assembly in the hippocampal CA1 SLM area, as evidenced by an enhanced ratio of GluR1 to GluR2 during chronic stress. This alteration in AMPARs was critical to memory retention, whereby memory retention was blunted by local blockage of CP-AMPARs in the SLM of naïve and exercised mice. Regular exercise improved PRL responsiveness in the hippocampal CA1 region during chronic stress, which led to increased binding of PRL to its receptor (PRLR) and PRL-dependent enhancement in phosphorylated signal transducer and activator of transcription 5 levels. The improvement in PRL responsiveness contributed to memory retention during chronic stress, as the protective action of exercise on memory persistence during stress was abolished by PRLR knockdown in the hippocampal CA1 area. Finally, in primary hippocampal cultures, repeated treatment with corticosterone led to decreased AMPAR-mediated Ca2+ influx, which was restored by PRL treatment. The above findings suggest a protective role for exercise against chronic stress-evoked defects in memory consolidation via PRL-modulated incorporation of CP-AMPARs into hippocampal CA1 synapses.

The ameliorating effect of exercise on long-term memory impairment and dendritic retraction via the mild activation of AMP-activated protein kinase in chronically stressed hippocampal CA1 neurons.

PURPOSE: Chronic stress affects the neuronal architecture of hippocampal subfields including the Cornu Ammonis 1 (CA1) region, which governs long-term memory. Exercise exerts a beneficial effect on memory improvement via hippocampal AMP-activated protein kinase (AMPK) activation. However, the relationship between the two phenomena is poorly understood. This study used animal and cell culture experimental systems to investigate whether chronic stress-induced impairment of memory consolidation and maladaptation of the neuronal architecture in the hippocampal CA1 area is prevented by regular exercise through AMPK activation. METHODS: Mice underwent four weeks of treadmill running with or without a 6h/21d-restraint stress regimen, along with treatment with Compound C. Memory consolidation was assessed using the Morris Water Maze (MWM). Dendritic rearrangement of hippocampal CA1 neurons was evaluated using the Golgi-Cox stain and Sholl analysis. Additionally, the primary hippocampal culture system was adopted for in vitro experiments. RESULTS: Chronic stress-induced failure of memory retention and reduction in AMPK activation were ameliorated by the exercise regimen. Chronic stress- or repeated corticosterone (CORT)- provoked malformation of the neuronal architecture was also suppressed by both exercise and treatment with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). CONCLUSION: Chronic stress causes dendritic retraction among dorsal hippocampal CA1 neurons via the downregulation of AMPK activation, thereby leading to failure of memory retention. In contrast, regular exercise protects against chronic stress-evoked defects in memory consolidation and changes in neuronal morphology in the dorsal hippocampal CA1 area via mild activation of AMPK.

Regular exercise and creatine supplementation prevent chronic mild stress-induced decrease in hippocampal neurogenesis via Wnt/GSK3ß/ß-catenin pathway.

PURPOSE: Chronic stress can lead to mood-related psychomotor behaviors such as despair. Decreased hippocampal neurogenesis has been observed in patients with depression and in animal models of depression. Exercise enhances the population of the new born cells in the dentate gyrus (DG). A few studies have demonstrated that creatine has antidepressant effects in humans. However, the mechanism underpinning these effects is poorly understood. Therefore, we examined whether regular exercise and/or creatine was closely associated with the activity of the Wnt/GSK3ß/ß-catenin pathway in the hippocampal DG. METHODS: Mice were subjected to 4 weeks of chronic mild stress starting a week prior to the start of a 4-week protocol of treadmill running and creatine supplementation. Tail suspension (TST) and forced swimming tests (FST) were carried out 2 days after the final treadmill running session. Immunohistochemical and western blot analyses were conducted to evaluate hippocampal neurogenesis, GSK3ß activity, and nuclear ß-catenin protein levels in the DG. Furthermore, Wnt signaling antagonism in the DG using stereotaxic injection was performed. RESULTS: Chronic mild stress-induced increase in immobility in the TST and FST were restored by treadmill running and/or creatine supplementation. The number of Ki-67+ and doublecortin (DCX)+ cells were decreased by chronic stress, and this decline was reversed by the exercise and supplement regimen, along with the changes in GSK3ß activity and nuclear ß-catenin protein levels in the DG. Local antagonism of DG Wnt signaling caused an increase in immobility even 5 days after injection with C59. CONCLUSION: Regular exercise combined with creatine supplementation had a greater effect on hippocampal neurogenesis via the Wnt/GSK3ß/ß-catenin pathway activation compared with each treatment in chronic mild stress-induced behavioral depression.

Role of Angptl4/Fiaf in exercise-induced skeletal muscle AMPK activation.

Angiopoietin-like protein 4 (Angptl4)/fasting-induced adipose factor (Fiaf) expression levels are increased by exercise in skeletal muscle. We have previously shown that Angptl4 regulates food intake and energy expenditure via modulation of hypothalamic AMP-activated protein kinase (AMPK) activity. AMPK is an important signaling molecule that integrates skeletal muscle metabolism during exercise. Therefore, we investigated the involvement of Angptl4 in exercise-induced AMPK activation in skeletal muscle. Angptl4 protein and mRNA expression levels were significantly increased in the gastrocnemius and soleus muscles of mice following a 50-min running bout. Treatment of C2C12 myotubes with Angptl4 increased phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), which were markers of AMPK activation, and the mitochondrial maximum respiratory capacity. Treadmill exercise increased AMPK and ACC phosphorylation in the gastrocnemius of normal mice; this phosphorylation increase was attenuated in mice lacking Angptl4. Endurance to swimming and hanging was also reduced in Angptl4 knockout mice. Taken together, our current data demonstrate that exercise-induced upregulation of skeletal muscle Angptl4 is critical for AMPK activation and exercise tolerance. These findings unveil a new role for skeletal muscle Angptl4 in exercise physiology. NEW & NOTEWORTHY 1) Angiopoietin-like protein 4 (Angptl4) treatment activates AMP-activated protein kinase (AMPK) signaling in skeletal muscle cells. 2) Angptl4 increases the maximum mitochondrial oxidative capacity through AMPK activation in skeletal muscle cells. 3) Lack of Angptl4 mitigates exercise-induced skeletal muscle AMPK activation. 4) Angptl4-deficient mice show a lower endurance to exercise.

Effects of acute high-Intensity resistance exercise on cognitive function and oxygenation in prefrontal cortex.

PURPOSE: Moderate-intensity exercise is known to be the best effective intensity to enhance cognitive function, including memory and learning. However, the effects of high-intensity exercise in comparison with moderate- intensity exercise on cognitive function remain controversial. The aim of this study was to investigate the effect of high-intensity resistance exercise on cognitive function. METHODS: Thirty-six healthy female college students volunteered to participate in this study. The participants were divided into four groups: (i) control group (CON); (ii) high-intensity resistance exercise group (HIR); (iii) high-intensity aerobic exercise group (HIA); and (iv) combined moderate-intensity exercise group (MIC). Immediately prior to and after exercise, the solved number (SN) and reaction times (RT) in the Stroop test (neutral task, NT and incongruent task, IT), as well as the tissue oxygen index (TOI) in the left and right prefrontal cortex (PFC) were measured in all groups. RESULTS: In the NT, both HIR and MIC groups showed significant improvements in SN and RT compared with the CON group. Meanwhile, performance in the HIA group was significantly attenuated compared with that in the MIC group. In the IT, only the MIC group showed a significant increase in SN and RT compared with the CON group. Furthermore, the TOI in the PFC (left PFC in the NT, and bilaterally in the IT) was significantly lower in the HIR group compared with that in the CON group. CONCLUSION: The results of this study show worse cognitive performance and decreased PFC oxygenation in high-intensity exercise compared with moderate-intensity exercise and controls. These results suggest that high-intensity exercise may not improve cognition as effectively as moderate-intensity exercise.

Arc/Arg3.1 protein expression in dorsal hippocampal CA1, a candidate event as a biomarker for the effects of exercise on chronic stress-evoked behavioral abnormalities.

PURPOSE: Chronic stress is a risk factor for behavioral deficits, including impaired memory processing and depression. Exercise is well known to have beneficial impacts on brain health. METHODS: Mice were forced to treadmill running (4-week) during chronic restraint stress (6h/21d), and then behavioral tests were conducted by Novel object recognition, forced swimming test: FST, sociality test: SI. Dissected brain was stained with anti-calbindin-d28k and anti-Arc antibodies. Also, mice were treated with CX546 intraperitoneally during chronic restraint stress, and behavioral tests were assessed using Morris water maze, FST, and SI. Dissected brain was stained with anti-Arc antibody. RESULTS: The current study demonstrated that chronic stress-induced impairment of memory consolidation and depression-like behaviors, along with the changes in calbindin-d28k and Arc protein levels in the hippocampal CA1 area, were attenuated by regular treadmill running. Further, prolonged ampakine treatment prevented chronic stress-evoked behavioral abnormalities and nuclear Arc levels in hippocampal CA1 neurons. Nuclear localization of Arc protein in hippocampal CA1 neurons, but not total levels, was correlated with behavioral outcome in chronically stressed mice in response to a regular exercise regimen. CONCLUSION: These results suggest that nuclear levels of Arc are strongly associated with behavioral changes, and highlight the role of exercise acting through an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR)-mediated mechanisms in a chronic stress-induced maladaptive condition.

l-Carnitine supplement reduces skeletal muscle atrophy induced by prolonged hindlimb suspension in rats.

l-Carnitine was recently found to downregulate the ubiquitin proteasome pathway (UPP) and increase insulin-like growth factor 1 concentrations in animal models. However, the effect of l-carnitine administration on disuse muscle atrophy induced by hindlimb suspension has not yet been studied. Thus, we hypothesized that l-carnitine may have a protective effect on muscle atrophy induced by hindlimb suspension via the Akt1/mTOR and/or UPP. Male Wistar rats were assigned to 3 groups: hindlimb suspension group, hindlimb suspension with l-carnitine administration (1250 mg·kg-1·day-1) group, and pair-fed group adjusted hindlimb suspension. l-Carnitine administration for 2 weeks of hindlimb suspension alleviated the decrease in weight and fiber size in the soleus muscle. In addition, l-carnitine suppressed atrogin-1 mRNA expression, which has been reported to play a pivotal role in muscle atrophy. The present study shows that l-carnitine has a protective effect against soleus muscle atrophy caused by hindlimb suspension and decreased E3 ligase messenger RNA expression, suggesting the possibility that l-carnitine protects against muscle atrophy, at least in part, through the inhibition of the UPP. These observations suggest that l-carnitine could serve as an effective supplement in the decrease of muscle atrophy caused by weightlessness in the fields of clinical and rehabilitative research.

Effects of creatine monohydrate supplementation and exercise on depression-like behaviors and raphe 5-HT neurons in mice.

PURPOSE: The effects of creatine and exercise on chronic stress-induced depression are unclear. In the present study, we identified the effects of 4-week supplementation of creatine monohydrate and/or exercise on antidepressant behavior and raphe 5-HT expression in a chronic mild stress-induced depressed mouse model. METHODS: Seven-week-old male C57BL/6 mice (n=48) were divided randomly into 5 groups: (1) non-stress control (CON, n=10), (2) stress control (ST-CON, n=10), (3) stress and creatine intake (ST-Cr, n=10), (4) stress and exercise (ST-Ex, n=9), and (5) combined stress, exercise, and creatine intake (ST-Cr+Ex, n=9). After five weeks' treatment, we investigated using both anti-behavior tests (the Tail Suspension Test (TST) and the Forced Swimming Test (FST)), and 5-HT expression in the raphe nuclei (the dorsal raphe (DR) and median raphe (MnR)). RESULTS: Stress for 4 weeks significantly increased depressive behaviors in the mice. Treatment with creatine supplementation combined with exercise significantly decreased depressive behaviors as compared with the CON-ST group in both the TST and FST tests. With stress, 5-HT expression in the raphe nuclei decreased significantly. With combined creatine and exercise, 5-HT positive cells increased significantly and had a synergic effect on both DR and MnR. CONCLUSION: The present study found that even a single treatment of creatine or exercise has partial effects as an antidepressant in mice with chronic mild stress-induced depression. Furthermore, combined creatine and exercise has synergic effects and is a more effective prescription than a single treatment.

Astaxanthin supplementation enhances adult hippocampal neurogenesis and spatial memory in mice.

SCOPE: There is a growing necessity for efficacious natural supplements with antioxidant effects on the brain, in particular, hippocampal function. One such compound, which also has a neuroprotective effect, is the carotenoid astaxanthin (ASX). Despite ASX's potential benefit to the brain, very little is known about its effect on hippocampal plasticity and cognition. Thus, we investigated the effect of ASX on adult hippocampal neurogenesis (AHN) and spatial memory using a mouse model. METHODS AND RESULTS: Dose-response was examined in mice fed ASX-supplemented diets (0, 0.02, 0.1, and 0.5%) to define the effect of ASX on AHN. In conjunction with AHN results, hippocampus-dependent cognitive function was assessed. We delineated molecular mechanisms associated with ASX-enhanced AHN using DNA microarray analysis. Results revealed that ASX enhanced cell proliferation and survival at 0.1% and 0.5% doses. Newborn mature neurons were higher only with 0.5% ASX, which also enhanced spatial memory. Transcriptomic profiling revealed potential AHN-associated molecules (Prl, Itga4, and Il4) that were ASX induced. Their downstream factors, identified through Ingenuity Pathway Analysis, were positively correlated with ASX-induced increases in spatial memory. CONCLUSION: ASX supplementation enhanced AHN and spatial memory, and a DNA microarray approach provided, for the first time, novel molecular insights into ASX action.

DNA microarray-based analysis of voluntary resistance wheel running reveals novel transcriptome leading robust hippocampal plasticity.

In two separate experiments, voluntary resistance wheel running with 30% of body weight (RWR), rather than wheel running (WR), led to greater enhancements, including adult hippocampal neurogenesis and cognitive functions, in conjunction with hippocampal brain-derived neurotrophic factor (BDNF) signaling (Lee et al., J Appl Physiol, 2012; Neurosci Lett., 2013). Here we aimed to unravel novel molecular factors and gain insight into underlying molecular mechanisms for RWR-enhanced hippocampal functions; a high-throughput whole-genome DNA microarray approach was applied to rats performing voluntary running for 4 weeks. RWR rats showed a significant decrease in average running distances although average work levels increased immensely, by about 11-fold compared to WR, resulting in muscular adaptation for the fast-twitch plantaris muscle. Global transcriptome profiling analysis identified 128 (sedentary × WR) and 169 (sedentary × RWR) up-regulated (>1.5-fold change), and 97 (sedentary × WR) and 468 (sedentary × RWR) down-regulated (<0.75-fold change) genes. Functional categorization using both pathway- or specific-disease-state-focused gene classifications and Ingenuity Pathway Analysis (IPA) revealed expression pattern changes in the major categories of disease and disorders, molecular functions, and physiological system development and function. Genes specifically regulated with RWR include the newly identified factors of NFATc1, AVPR1A, and FGFR4, as well as previously known factors, BDNF and CREB mRNA. Interestingly, RWR down-regulated multiple inflammatory cytokines (IL1B, IL2RA, and TNF) and chemokines (CXCL1, CXCL10, CCL2, and CCR4) with the SYCP3, PRL genes, which are potentially involved in regulating hippocampal neuroplastic changes. These results provide understanding of the voluntary-RWR-related hippocampal transcriptome, which will open a window to the underlying mechanisms of the positive effects of exercise, with therapeutic value for enhancing hippocampal functions.

The blood lactate increase in high intensity exercise is depressed by Acanthopanax sieboldianus.

This study investigates the anti-fatigue effects of Acanthopanax sieboldianus (A. sieboldianus) at various exercise intensities. Two experiments were conducted in 18 Sprague-Dawley rats. In Experiment 1, a three-stage increment test (15 m/min for 5 min, and 20 m/min for 5 min and 25 m/min for 10 min) was performed using a treadmill. In Experiment 2, a 10-min swimming test was conducted. Blood samples were extracted from each rat before, during and after the exercises and the blood concentrations of lactate and glucose measured. In both experiments, water (control) or A. sieboldianus solution (ASS) was administered orally using a zonde 30 min before the exercise. In the swimming test, ASS administration significantly decreased the blood lactate level measured at the end of the exercise and 5 min post-exercise relative to the water group, although the two groups did not differ significantly in the treadmill test. Our study demonstrates that a single oral administration of A. sieboldianus prior to high-intensity exercise significantly decreases the blood lactate concentration suggesting that A. sieboldianus has an intrinsic anti-fatigue effect.

Hypothalamic and pituitary clusterin modulates neurohormonal responses to stress.

Clusterin is a sulfated glycoprotein abundantly expressed in the pituitary gland and hypothalamus of mammals. However, its physiological role in neuroendocrine function is largely unknown. In the present study, we investigated the effects of intracerebroventricular (ICV) administration of clusterin on plasma pituitary hormone levels in normal rats. Single ICV injection of clusterin provoked neurohormonal changes seen under acute stress condition: increased plasma adrenocorticotropic hormone (ACTH), corticosterone, GH and prolactin levels and decreased LH and FSH levels. Consistently, hypothalamic and pituitary clusterin expression levels were upregulated following a restraint stress, suggesting an involvement of endogenous clusterin in stress-induced neurohormonal changes. In the pituitary intermediate lobe, clusterin was coexpressed with proopiomelanocortin (POMC), a precursor of ACTH. Treatment of clusterin in POMC expressing AtT-20 pituitary cells increased basal and corticotropin-releasing hormone (CRH)-stimulated POMC promoter activities and intracellular cAMP levels. Furthermore, clusterin treatment triggered ACTH secretion from AtT-20 cells in a CRH-dependent manner, indicating that increased clusterin under stressful conditions may augment CRH-stimulated ACTH production and release. In summary, hypothalamic and pituitary clusterin may function as a modulator of neurohormonal responses under stressful conditions.

Effect of HX108-CS supplementation on exercise capacity and lactate accumulation after high-intensity exercise.

BACKGROUND: In the present study, we determined the effects of HX108-CS (mixed extract of Schisandra chinensis and Chaenomeles sinensis) supplementation on lactate accumulation and endurance capacity. Furthermore, we examined CK (creatine kinase), LDH (lactate dehydrogenase) activity to determine whether the HX108-CS affected markers of skeletal muscle injury in vivo and in vitro. METHODS: Exercise capacity was measured by an exhaustive swimming test using ICR mice divided into four groups; one group received distilled water (DW) (Control group, n = 10), and the other groups received three different dosages of HX108-CS (10, 50 and 100 mg/kg, n = 10 per group) solution in water orally. Then, for the time-dependent measurements of blood lactate, CK, and LDH, Sprague-Dawley rats were divided into two groups; one received DW (Control group, n = 10), and the other group received HX108-CS (100 mg/kg, n = 10) solution in the same way as mice. Before the exercise test, the animals were given either DW or HX108-CS for 2 weeks. High-intensity treadmill exercise was performed for 30 minutes. Blood samples were collected and analyzed during and after exercise. For the in vitro experiment, C2C12 cells were treated with HX108-CS to examine its effect on lactate production, CK, and LDH activity. RESULTS: Blood lactate concentration was significantly lowered immediately after treadmill exercise in HX108-CS group; however, there were no significant differences in activities of CK and LDH between HX108-CS and control during treadmill exercise and recovery phase. Furthermore, treatment with 100 mg/kg of HX108-CS led to a significant increase in the time to exhaustion in swimming test, and concurrently blood lactate concentration was significantly decreased in 50 and 100 mg/kg treated group. Moreover, our results of in vitro experiment showed that HX108-CS suppressed lactate production, CK, and LDH activity in a dose-dependent manner. CONCLUSIONS: These results suggest that supplementation with HX108-CS may enhance exercise capacity by lowering lactate accumulation. This may in part be related to an amelioration of skeletal muscle injury.

Exercise ameliorates cognition impairment due to restraint stress-induced oxidative insult and reduced BDNF level.

We assessed whether chronic treadmill exercise attenuated restraint stress-induced cognition impairment. Although serum corticosterone was not significantly altered by exercise, the restraint-induced increases in hippocampal malondialdehyde (MDA) and 4-hydroxynonenal (HNE) were reduced by chronic exercise. The exercise paradigm also reversed stress-induced reductions in brain-derived neurotrophic factor (BDNF), which increased cAMP response element-binding protein (CREB) and AKT activation. We verified the relationship between oxidative stress and BDNF signaling by treating primary hippocampal cultures with hydrogen peroxide (H2O2), which reduced BDNF and phosphorylated CREB and AKT (p-CREB, p-AKT) in a dose-dependent manner. Notably, pretreatment with N-acetylcysteine (NAC) reversed these decreases in a dose-dependent manner. These findings suggest that chronic exercise can ameliorate repeated stress-induced cognitive impairment by detoxifying reactive oxygen species (ROS) in the hippocampus and activating BDNF signaling.

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.

Effects of blood flow to the prefrontal cortex on high-intensity exercise combined with high-decibel music.

We studied the effects of high-intensity exercise (70-75% of VO2 max) combined with high-decibel music (100 dB) on cognitive function (measured by the Stroop test) and related blood flow changes to the prefrontal cortex (measured by Oxy-hemoglobin (Hb), Deoxy-Hb, tissue oxygen index (TOI), and normalized tissue hemoglobin index (nTHI)). The subjects of the study were 28 healthy female university students in their early 20s. Subjects were categorized into control group (CG), music group (MG), exercise group (Ex), and music and exercise group (MnEx). A crossover design was implemented so that all subjects participated in all test groups. We found no significant difference in reaction time between CG and MG for the neutral and incongruent tasks of Stroop test. However, there were significant improvements in the neutral and incongruent tasks for both the Ex (p < 0.01) and MnEx (p < 0.01) groups. Oxy-Hb measurements in the prefrontal cortex of the brain supported the Stroop test data. We found no difference between Ex and MnEx in the TOI; however, there was a significant decrease (p < 0.05) in MnEx compared to Ex. In addition, Ex resulted in a significant increase (p < 0.05) in nTHI as compared to CG. These results indicate that high decibel music could negatively affect prefrontal cortex activation of the brain during exercise.

Ultra-weak photon emission during wrist curl and cycling exercises in trained healthy men.

Human ultra-weak photon emission (UPE) is related to the activity of respiratory chain and oxygen consumption. Investigations on UPE and its response to exercise are almost non existent. Since human UPE is an indicator of reactive oxygen species (ROS) levels, we used exercises as a model to study UPE. To continue the research on the relationship between human UPE and exercise, it was decided to carry out measurements of UPE in response to different exercise modes with 20 healthy male subjects. The performed exercises were wrist curls with a dumbbell and indoor cycling. Regarding wrist curl exercises, 70% of the subjects for the first exercise and 65% for the second exercise did not show any significant changes in UPE. Also, the statistical analysis did not show significant changes of the UPE levels. In terms of cycling exercise, 85% of subjects did not show any significant increase of UPE. The gathered data showed that a majority of the subjects didn't show an increase of the UPE during both types of exercises. Our results imply that the UPE is not only affected by oxygen consumption, but also by the intensity, the type of exercise, and the physiology of the subject.