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 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.

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.

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

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

The 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.

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.

Exercise training improves basal blood glucose metabolism with no changes of cytosolic inhibitor B kinase or c-Jun N-terminal kinase activation in skeletal muscle of Otsuka Long-Evans Tokushima fatty rats.

Redox-sensitive stress kinases and heat shock protein 72 (Hsp72) have been considered to be associated with the development of type 2 diabetes in skeletal muscle. However, the effect of exercise training on skeletal muscle of type 2 diabetic models is largely unknown. The purpose of this study was to investigate the effect of 12 weeks of exercise training on gastrocnemius of type 2 diabetic rats, by examining the activation of c-Jun N-terminal kinase (JNK), the nuclear factor B (NF-B) pathway and Hsp72. Total hydroperoxide and 4-hydroxynoneal, as oxidative stress markers, were also examined. Otsuka Long-Evans Tokushima fatty (OLEFT) rats were randomly divided into an exercise training group (Ex-OLETF, n = 8) and a sedentary group (Sed-OLETF, n = 8), while Long-Evans Tokushima Otsuka (LETO) rats were used as a control group (Con-LETO, n = 5). The Ex-OLETF rats were trained on a treadmill five times a week for 12 weeks. The levels of hydroperoxide and 4-hydroxynoneal in both Ex-OLETF and Sed-OLETF were significantly higher compared with Con-LETO, but there was no difference between Ex-OLETF and Sed-OLETF. Levels of inhibitor B kinase, JNK activation and p65 nuclear translocation followed a similar pattern to that observed in oxidative stress markers. The level of Hsp72 in Ex-OLETF was increased by exercise training, but it did not reach the level observed in Con-LETO. The NF-B DNA binding activity in Sed-OLETF was significantly higher compared with Con-LETO. Although it was not statistically significant, exercise training in Ex-OLETF showed a trend to reduce the activation of NF-B DNA binding activity compared with Sed-OLETF (P = 0.104). Our findings indicate that exercise training improves basal glucose metabolism without a change in stress kinases, and that nuclear regulation of NF-B activity in diabetic muscle could be regulated independently of the cytosolic pathway. Our study also suggests a possibility that exercise-induced Hsp72 serves as a protective mechanism in skeletal muscle of OLETF rats.

Characteristics of maximum performance of pedaling exercise in recumbent and supine positions.

To determine the characteristics of maximum pedaling performance in the recumbent and supine positions, maximum isokinetic leg muscle strength was measured in eight healthy male subjects during pedaling at three velocities (300°/s, 480°/s, and 660°/s), and maximum incremental tests were performed for each position. The maximum isokinetic muscle strength in the recumbent position was 210.0 ± 29.2 Nm at 300°/s, 158.4 ± 19.8 Nm at 480°/s, and 110.6 ± 13.2 at 660°/s. In contrast, the muscle strength in the supine position was 229.3 ± 36.7 Nm at 300°/s, 180. 7 ± 20.3 Nm at 480°/s, and 129.6 ± 14.0 Nm at 660°/s. Thus, the maximum isokinetic muscle strength showed significantly higher values in the supine position than in the recumbent position at all angular velocities. The knee and hip joint angles were measured at peak torque using a goniometer; the knee joint angle was not significantly different between both positions, whereas the hip joint angle was greater in the supine position than in the recumbent position (Supine position: 137.3 ± 9. 33 degree at 300°/s, 140.0 ± 11.13 degrees at 480°/s, and 141.0 ± 9.61 degrees at 660°/s. Recumbent position: 99.5 ± 12.21 degrees at 300°/s, 101.6 ± 12.29 degrees at 480°/s, and 105.8 ± 14.28 degrees at 660°/s). Peak oxygen uptake was higher in the recumbent position (50.3 ± 4.43 ml·kg(-1)·min(-1)) than in the supine position (48.7 ± 5.10 ml·kg(-1)·min(-1)). At maximum exertion, the heart rate and whole-body rate of perceived exertion (RPE) were unaffected by position, but leg muscle RPE was higher in the supine position (19.5 ± 0.53 than in the recumbent position (18.8 ± 0.71). These results suggest that the supine position is more suitable for muscle strength exertion than the recumbent position, and this may be due to different hip joint angles between the positions. On the contrary, the endurance capacity was higher in the recumbent position than in the supine position. Since leg muscle RPE was higher in the supine position than in the recumbent position, it was suggested that different burdens imposed on active muscles in both positions exerted an impact on the result of the endurance capacity. Key pointsIsokinetic maximal peak torque measured in this study during pedaling showed higher values in the supine position than in the recumbent position at all angular velocities.Maximum oxygen uptake as evaluated by maximum incremental testing showed higher values in the recumbent position than in the supine position.No significant changes in the angle of peak torque for the knee joint or hip joint were observed in either the recumbent or supine position even at an increased angular velocity. These observations indicate the effectiveness of a cycle-type muscle strength assessment device for evaluating leg muscle strength.

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.

Comparison of Lactate Threshold, Glucose, and Insulin Levels Between OLETF and LETO Rats After All-Out Exercise.

Otsuka Long-Evans Tokushima Fatty (OLETF) rats are an animal model for obesity and Non Insulin Dependent Diabetes Mellitus by hyperphagia. The lactate threshold (LT) is used to determinate aerobic capacity and exercise intensity in individuals. The purpose of this study was to determine whether velocity at the LT (VLT), glucose, and insulin levels of OLETF differs from Long-Evans Tokushima (LETO) rats after all-out exercise on treadmill running. In the results, we found that VLT level of OLETF rats (17.8 ± 1.39 m·min(-1)) was significantly lower than that of the LETO rats (20.5 ± 1.33 m·min(-1)). The blood glucose levels immediately after all-out exercise increased in OLETF (from 7.23 ± 0.36 to 9.38 ± 1.77 mmol·L(-1)) and decreased in LETO rats (from 6.36 ± 0.27 to 4.42 ± 0.71 mmol·L(-1)), and the insulin level was decreased in both the OLETF (from 34.4 ± 7.7 to 20.13 ± 8.63 µU·mL(-1)) and LETO (from 15.29 ± 2.6 to 5.72 ± 1.49 µU·mL(-1)) rats immediately after the all-out exercise, but the difference was not significant. Our results suggest that the different VLT, blood glucose and insulin levels should be considered to compensate for the differences between the OLETF and LETO rats. Moreover, the VLT will be a useful reference for the future studies on exercise training of OLETF rats. Key pointsThe VLT of OLETF was significantly lower than that of LETO rats.The changes of the blood lactate levels from rest to all-out exercise showed significant difference between OLETF and LETO rats.The result of low VLT in the OLETF compared to LETO rats implies that the application of relatively low exercise intensity is suitable for OLETF rats.The different VLT should be recognized to compensate for the differences between the OLETF and LETO rats.

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.

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.

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.

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.

Inhibitory effects of an orexin-2 receptor antagonist on orexin A- and stress-induced ACTH responses in conscious rats.

Orexins, recognized for their diverse functions in sleep/wakefulness/arousal and appetite regulation, may play provocative roles in stress response. Although the PVN of the hypothalamus expresses an abundance of orexin-2 receptor (OX-2R), the involvement of OX-2R in regulating ACTH response to stress remains unclear. To address this, we examined effects of a selective antagonist to OX-2R (N-{(1S)-1-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]carbonyl}-2,2-dimethylpropyl)-N-{4-pyridinylmethyl}amine upon plasma ACTH concentrations after administration of orexin A and swimming stress. Increases in ACTH levels with orexin A or swimming stress were attenuated with prior administration of an OX-2R antagonist. These results suggest that swimming stress facilitates ACTH release, at least in part via activation of OX-2R.

Threshold-like pattern of neuronal activation in the hypothalamus during treadmill running: establishment of a minimum running stress (MRS) rat model.

Despite the indication that the hypothalamo-pituitary-adrenal (HPA) axis is activated during treadmill running, there have not been any studies focusing on the relationship between exercise intensity and region-specific neural activities in hypothalamus. To address this, rats were subjected to 30 min of running, either at middle (supra-LT, 25 m min(-1)) or low speeds (sub-LT, 15 m min(-1)), and c-Fos-(+) cells were counted and compared with control rats. Significant increases in blood glucose and lactate levels, and plasma ACTH and osmolality levels were observed during supra-LT running. Only supra-LT running significantly increased c-Fos induction in various hypothalamic regions, namely, the medial preoptic area (MPO), periventricular nucleus (Pe), suprachiasmatic nucleus (SCN), supraoptic nucleus (SON), parvocellular division of the paraventricular nucleus (pPVN), anterior hypothalamic area (AH), arcuate nucleus (ARC) and posterior hypothalamic nucleus (PH). However, sub-LT caused no effect on c-Fos accumulation. This indicates that the hypothalamus responds uniquely to running in a threshold-like pattern distinct from the speed-dependent pattern previously reported for the medulla oblongata [Ohiwa et al., 2006a,b]. In addition, these results showed a physiologic basis for mild exercise useful for establishing our minimum running stress (MRS) rat model, or the running conditions that minimize the activation of the HPA axis.

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.

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.

Differential responsiveness of c-Fos expression in the rat medulla oblongata to different treadmill running speeds.

Expression of the inducible transcription factor c-Fos was mapped in the rat medulla oblongata to identify the brain areas respond to different running speeds. Rats were subjected to 30 min of running, either at high speed, low speed or just sitting on a treadmill (control). Blood lactate levels were measured to confirm the physiological impact of different exercise intensities. The number of c-Fos-ir cells was counted and their spatial distributions were mapped through the rostral to the caudal level in the medulla. A statistically significant exercise intensity-dependent induction of c-Fos was observed in the nucleus of the solitary tract (NTS) and caudal ventrolateral medulla (CVL) in the medulla. Further, c-Fos induction was more predominant in the caudal part of each nucleus. The present data clearly show that different running speeds cause differential activation of each nucleus in the medulla, and in particular, the caudal parts of the NTS and the CVL are the most responsive to speed changes. The present study identifies brain areas newly found to be responsive to changes in running speed. These findings are likely to be particularly helpful in studies of specific neural circuits and their functions in response to different running speeds.

Activation of A1 and A2 noradrenergic neurons in response to running in the rat.

Since running accompanied with blood lactate accumulation stimulates the release of adrenocorticotropic hormone (ACTH), running above the lactate threshold (LT) acts as stress (running stress). To examine whether A1/A2 noradrenergic neurons that project to the hypothalamus activate under running stress, c-Fos immunohistochemistry was used to compare the effects of running with or without stress response on A1/A2 noradrenergic neurons. Blood lactate and plasma ACTH concentrations significantly increased in the running stress group, but not in the running without stress response and control groups, confirming different physiological impacts between different intensity of running with or without stress. Running stress markedly increased c-Fos accumulation in the A1/A2 noradrenergic neurons. Running without stress response also induced a significant increase in c-Fos expression in the A1/A2 noradrenergic neurons, and the percentage of the increase was smaller than that of running stress. The extent of c-Fos expression in the A1/A2 noradrenergic neurons correlates with exercise intensity, signifying that this neuronal activation is running speed-dependent. We thus suggest that A1/A2 noradrenergic neurons are activated in response to not only running stress, but also to other physiological running, enhanced by non-stressful running. These findings will be helpful in studies of specific neurocircuits and in identifying their functions in response to running at different intensities.