Naloxone potentiates treadmill running-induced increase in c-Fos expression in rat hippocampus

The expression of c-Fos is induced by a variety of stimuli and is sometimes used as a marker for increased neuronal activity. In the present study, the effect of treadmill running on c-Fos expression in the hippocampus and the involvement of opioid receptors were investigated via c-Fos immunohistochemistry. It was shown that c-Fos expression in the CA1 region, the CA2 and CA3 regions, and the dentate gyrus of the hippocampus was significantly increased by treadmill running and naloxone, a nonselective opioid receptors antagonist, treatment enhanced treadmill exercise-induced increase of hippocampal c-Fos expression. Base on the present results, it can be suggested that treadmill running increases hippocampal neuronal activity and that endogenous opioids curtail the exercise-induced increase.     

Neurobiology of Mice Selected for High Voluntary Wheel-running Activity

Selective breeding of house mice has been used to study theevolution of locomotor behavior. Our model consists of 4 replicatelines selectively bred for high voluntary wheel running (High-Runner)and 4 bred randomly (Control). The major changes in High-Runnerlines appear to have taken place in the brain rather than incapacities for exercise. Their neurobiological profile resemblesfeatures of human Attention Deficit Hyperactivity Disorder (ADHD)and is also consistent with high motivation for exercise asa natural reward. Both ADHD and motivation for natural rewards(such as food and sex), as well as drugs of abuse, have beenassociated with alterations in function of the neuromodulatordopamine, and High-Runner mice respond differently to dopaminedrugs. In particular, drugs that block the dopamine transporterprotein (such as Ritalin and cocaine) reduce the high-intensityrunning of High-Runner mice but have little effect on Controlmice. In preliminary studies of mice exercised on a treadmill,brain dopamine concentrations did not differ, suggesting thatchanges in the dopamine system may have occurred downstreamof dopamine production (e.g., receptor expression or transduction).Brain imaging by immunohistochemical detection of c-Fos identifiedseveral key regions (prefrontal cortex, nucleus accumbens, caudate-putamen,lateral hypothalamus) that appear to play a role in the differentialresponse to Ritalin and in the increased motivation for runningin High-Runner mice. The activation of other brain regions,such as the hippocampus, was closely associated with wheel runningitself. Chronic wheel running (several weeks) also increasedthe production of new neurons to apparently maximal levels inthe hippocampus, but impaired learning in High-Runner mice.We discuss the biomedical implications of these findings.     

Effect of Treadmill Exercise on Blood Glucose,Serum Corticosterone Levels and Glucocorticoid Receptor Immunoreactivity in the Hippocampus in Chronic Diabetic Rats

Abnormal excess of glucocorticoid is one of feature characteristics in type 2 diabetes. In the present study, we investigated the effect of treadmill exercise at chronic diabetic stages on glucocorticoid receptor (GR) immunoreactivity in the hippocampal CA1 region and dentate gyrus, which are very vulnerable to diabetes. For this study, we used Zucker diabetic fatty (ZDF) rats and Zucker lean control (ZLC) rats. Twenty-three-week-old ZLC and ZDF rats were put on the treadmill with or without running for 7 weeks and sacrificed at 30 weeks of age. Treadmill exercise significantly decreased diabetes-induced blood glucose and serum corticosteroid levels although they did not drop to control levels. In sedentary ZLC rats, GR immunoreactivity was detected in pyramidal cells of the CA1 region as well as in granule cells of the dentate gyrus. In the sedentary ZDF rats, GR immunoreactivity was significantly increased in these regions. However, treadmill exercise significantly decreased GR immunoreactivity in these regions. These results indicate that treadmill exercise in chronic diabetic rats significantly decreased GR immunoreactivity in the hippocampal CA1 region and dentate gyrus, although blood glucose and serum corticosteroid levels did not fully recover to normal state.     

跑台运动改善海马线粒体功能提高APP/PS1小鼠学习记忆能力

为研究跑台运动对APP/PS1小鼠海马线粒体融合、分裂作用的影响,将遗传背景为C57BL/6的3月龄APP/PS1小鼠和野生小鼠各42只分别随机分为APP/PS1安静对照组（ADC,n=21）和运动组（ADE,n=21）,野生安静对照组（WTC,n=21）和运动组（WTE,n=21）。ADE、WTE组进行12周跑台运动,同时ADC、WTC组置于安静跑台环境。水迷宫实验检测小鼠的空间学习记忆能力,RT-PCR法检测线粒体功能关键酶的mRNA水平,Western印迹检测海马融合、分裂及线粒体关键酶的蛋白质表达情况,透射电镜观察海马线粒体融合、分裂状态。结果发现,6月龄APP/PS1小鼠学习记忆能力降低（P<0.05）;海马线粒体融合蛋白质Mfn1、Mfn2、Opa1表达降低（P<0.05）,线粒体分裂蛋白质Drp1、Mff表达增高（P<0.05）;线粒体膜结构模糊,嵴不明显,线粒体碎片增多,空泡化线粒体增多;线粒体呼吸关键酶COX IV及ATP合酶表达均下调（P<0.05）。12周跑台运动可逆转APP/PS1小鼠的上述变化,改善海马线粒体结构和功能,提高学习记忆能力。综上提示：12周跑台运动改善APP/PS1小鼠学习记忆能力的机制可能与其对线粒体结构与功能的改善有关。     

Estradiol treatment increases CCK-induced c-Fos expression in the brains of ovariectomized rats

The ovarian hormone estradiol reduces meal size and food intake in female rats, at least in part by increasing the satiating potency of CCK. Here we used c-Fos immunohistochemistry to determine whether estradiol increases CCK-induced neuronal activation in several brain regions implicated in the control of feeding. Because the adiposity signals leptin and insulin appear to control feeding in part by increasing the satiating potency of CCK, we also examined whether increased adiposity after ovariectomy influences estradiol's effects on CCK-induced c-Fos expression. Ovariectomized rats were injected subcutaneously with 10 microg 17beta-estradiol benzoate (estradiol) or vehicle once each on Monday and Tuesday for 1 wk (experiment 1) or for 5 wk (experiment 2). Two days after the final injection of estradiol or vehicle, rats were injected intraperitoneally with 4 microg/kg CCK in 1 ml/kg 0.9 M NaCl or with vehicle alone. Rats were perfused 60 min later, and brain tissue was collected and processed for c-Fos immunoreactivity. CCK induced c-Fos expression in the nucleus of the solitary tract (NTS), area postrema (AP), paraventricular nucleus of the hypothalamus (PVN), and central nucleus of the amygdala (CeA) in vehicle- and estradiol-treated ovariectomized rats. Estradiol treatment further increased this response in the caudal, subpostremal, and intermediate NTS, the PVN, and the CeA, but not in the rostral NTS or AP. This action of estradiol was very similar in rats tested before (experiment 1) and after (experiment 2) significant body weight gain, suggesting that adiposity does not modulate CCK-induced c-Fos expression or interact with estradiol's ability to modulate CCK-induced c-Fos expression. These findings suggest that estradiol inhibits meal size and food intake by increasing the central processing of the vagal CCK satiation signal.     

The Dose-Dependent Antioxidant Effects of Physical Exercise in the Hippocampus of Mice

Exercise increases both the consumption of oxygen and the production of reactive species in biological tissues, and this is counterbalanced by antioxidant adaptations to regular physical training. When the intensity of exercise fluctuates between mild and moderate, it improves the status of reduction–oxidation balance in the brain and induces neuroplasticity. However, intense exercise can oxidize the brain and impair neurological function. The effect of the frequency of exercise, which is an important factor in physical training, is still unknown. The effect of periodic exercise on biomarkers of oxidative stress in the hippocampus of mice was evaluated in this study. Mice were made to run on a treadmill for 8 weeks, two, three, or five times per week, and their hippocampi and quadriceps femoris muscles were then dissected. Biomarkers of oxidative damage were negatively correlated with the frequency of exercise and mitochondrial muscular activity, while the sulfhydryl contents were positively correlated with exercise frequency. A logistic analysis revealed a dose-dependent effect of exercise on these biomarkers. In summary, these results suggested that manipulating the frequency of physical exercise could induce antioxidant-related adaptations in the hippocampi of adult mice.     

Cardiorespiratory response to low-intensity walking in water and on land in elderly women.

The purpose of the present study was to determine whether or not the exercise intensity of water-walking for elderly women could be accurately prescribed by heart rate data obtained during treadmill exercise on land. Six healthy female volunteers, with a mean age of 62.2 +/- 4.2 years, took part in this study. Walking on land was performed on a treadmill. Each subject completed three consecutive 4-minute walks at a progressively increasing velocity (40, 60 and 80 m.min-1), with a 1-minute rest after both the first and second walks. The room temperature and relative humidity were 24.5 +/- 0.2 degrees C and 54.8 +/- 4.0%, respectively. Walking in water was performed in a Flowmill, which is a treadmill positioned at the base of a water flume. Each subject completed three consecutive 4-minute walks at a progressively increasing belt and water-flow velocity (20, 30 and 40 m.min-1), with a 1-minute rest after both the first and second walks. The water depth was at the level of the xiphoid process of each subject. The water temperature was 30.7 +/- 0.1 degrees C. The exercise intensity at the highest workrate was equivalent to 44.2 +/- 10.3% of the heart rate reserve (HRR) during water-walking and 38.4 +/- 4.7% of the HRR during land-walking. There was a highly significant linear relationship between heart rate (HR) and oxygen uptake (VO2) during both water-walking and land-walking. The relationship between HR and VO2 in both exercise modes was similar. Thus, the relationship of HR to VO2 derived from a treadmill-graded walking test on land may be used to prescribe exercise intensity for water-walking in thermoneutral water.     

60 Hz magnetic fields and central cholinergic activity: effects of exposure intensity and duration.

In previous research, we have found that acute exposure to a 60 Hz magnetic field caused a decrease in cholinergic activity in the frontal cortex and hippocampus of the rat. In the present study, the effects of exposure to different intensities of the magnetic field and durations of exposure were investigated. Rats were exposed to a 60 Hz magnetic field for 60 min at a flux density of either 0.5, 1.0, 1.5, or 2.0 mT. A significant decrease in cholinergic activity was observed in the frontal cortex and hippocampus immediately after exposure to the 2.0 mT field. No significant effect was observed at lower intensities. In another experiment, effect of exposure to a 1.0 mT magnetic field for 30, 45, 60, and 90 min was investigated. A decrease in cholinergic activity was found in both brain areas after 90 min of exposure. No significant effect was observed after shorter durations of exposure. In a further experiment, the exposure duration was extended to 3 h at flux densities of 0.5, 0.1, and 0.05 mT. A significant decrease in cholinergic activity was observed in the frontal cortex and hippocampus of the rat immediately after exposure to all the intensities. It is concluded that the intensity and duration of exposure interact. By increasing the duration of exposure, effects can be observed at lower intensities.     

Effect of exercise and suspensory on scrotal surface temperature in the stallion

In this study, the effect of exercise (treadmill, riding) on scrotal surface temperature (SST) in the stallion with and without suspensory was evaluated. Experiments were carried out between September and November 2004 using 12 Franches-Montagnes stallions from the National Stud in Avenches (Switzerland). Each stallion performed a standardized incremental treadmill and a ridden test with and without suspensory. The intensity of exercise was monitored by heart rate and blood lactate concentration. For SST measurements, special thermistors were developed and affixed to the most ventral part of the scrotum over each testis. SST was recorded telemetrically at 1min intervals. Our results show that type of exercise (treadmill/ridden) and suspensory (with/without) significantly influenced SST. The mean SST level was higher during treadmill (32.2+/-0.02 degrees C) than during ridden exercise (30.4+/-0.03 degrees C) and mean SST differences between stallions with and without suspensory were smaller in treadmill (0.4 degrees C) than in ridden (2 degrees C) exercise. These findings clearly demonstrate that ambient airflow, which was higher during ridden exercise, is important and effective in SST regulation. In order to prevent possible thermal damage to spermatogenic cells we recommend removing the suspensory immediately after exercise.     

Fibrinolytic activity is not dependent upon exercise mode in post-myocardial infarction patients

In this study we investigated possible differences in fibrinolytic activity in cardiac patients while they performed treadmill and cycle ergometry. Thirteen post-myocardial infarction patients completed two maximal exercise tests on treadmill and cycle ergometers. Blood was collected before and after each exercise test and was analyzed for the fibrinolytic variables, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activity, and lactate. Maximal oxygen uptake, heart rate, and ventilation were greater (P < 0.05) on the treadmill than during cycle ergometry, however, blood lactate was similar between modes. t-PA activity significantly increased with exercise (P < 0.05) and there was a trend toward a reduction in PAI-1 activity with exercise, but this did not reach statistical significance. The fibrinolytic responses to maximal exercise did not differ between the two modes of exercise studied. Therefore, exercise intensity, but not the mode of exercise, appeared to be the primary determinant of the fibrinolytic response to acute exercise in these patients. Accepted: 29 January 1998     

负重爬梯与有氧跑台运动对糖尿病大鼠学习记忆能力的影响及其机制探讨

目的：研究负重爬梯与有氧跑台运动对糖尿病大鼠学习记忆能力的改善效果并探索其可能分子机制。方法：40只雄性大鼠,随机分为正常对照组（NC）、糖尿病对照组（DC）、糖尿病负重爬梯组（DL）和糖尿病有氧跑台组（DA）,以单次腹腔注射链脲佐菌素构建糖尿病大鼠模型。DL组在晚上进行负重爬梯训练,10次/组×3组/天,每次间歇2 min,6天/周×6周;DA组在同一时间进行20 m/min的跑台训练,30 min/d。于造模成功和运动干预结束后采用Morris水迷宫检测大鼠的学习记忆能力;第2次水迷宫测试结束后断颈处死大鼠,采用RT-QPCR法检测大鼠海马内脑源性神经营养因子（BDNF）、TRKB、CREB mRNA表达水平。结果：与NC组相比,DC组大鼠海马BDNF、CREB基因表达显著下降,学习记忆能力显著降低。与DC组相比,DL和DA组大鼠海马BDNF、CREB基因表达显著上调,学习能力显著提高;DL大鼠海马TrkB基因显著上调,大鼠空间记忆能力显著改善,而DA组大鼠海马TrkB基因无显著变化,大鼠空间记忆能力无改善,与DA组相比,DL组大鼠海马TRKB、CREB基因显著上调。结论：有氧跑台运动与负重爬梯运动介导BDNF/TrkB/CREB信号通路对糖尿病大鼠的学习能力均有促进作用,而负重爬梯运动对糖尿病大鼠记忆能力的改善优于有氧运动方式。     

Hyper-response to Novelty Increases c-Fos Expression in the Hippocampus and Prefrontal Cortex in a Rat Model of Schizophrenia

Schizophrenia is a debilitating disorder that may have a neurodevelopmental origin. For this reason, animal models based on neonatal insults or manipulations have been extensively used to demonstrate schizophrenia-related behaviors. Among those, the neonatal ventral hippocampus lesion (nVHL) is largely used as a model of schizophrenia-related behavior as it mimics behavioral and neurochemical abnormalities often seen in schizophrenic patients including hyperlocomotion in a novel environment. To investigate the neuroanatomical basis of coding novelty in the nVHL rat, we assessed the behavioral locomotor activity paradigm in a novel environment and measured expression of c-Fos, a marker of neural activation, in brain regions involved in the process of coding novelty or locomotion. Upon reaching adulthood, nVHL rats showed hyperlocomotion in the novel environment paradigm. Moreover, in nVHL rats the expression of c-Fos was greater in the prefrontal cortex (PFC) and CA1 region of the dorsal hippocampus compared to sham rats. Whereas similar expression of c-Fos was observed in the basolateral amygdala, nucleus accumbens and dentate gyrus region of  hippocampus of nVHL and sham rats. These results suggest that the nVHL disrupts the neural activity in the PFC and CA1 region of hippocampus in the process of coding novelty in the rat.     

Long-term treadmill exercise improves spatial memory of male APPswe/PS1dE9 mice by regulation of BDNF expression and microglia activation

Increasing evidence suggests that physical activity could delay or attenuate the symptoms of Alzheimer''s disease (AD). But the underlying mechanisms are still not fully understood. To investigate the effect of long-term treadmill exercise on the spatial memory of AD mice and the possible role of β-amyloid, brain-derived neurotrophic factor (BDNF) and microglia in the effect, male APPswe/PS1dE9 AD mice aged 4 months were subjected to treadmill exercise for 5 months with 6 sessions per week and gradually increased load. A Morris water maze was used to evaluate the spatial memory. Expression levels of β-amyloid, BDNF and Iba-1 (a microglia marker) in brain tissue were detected by immunohistochemistry. Sedentary AD mice and wildtype C57BL/6J mice served as controls. The results showed that 5-month treadmill exercise significantly decreased the escape latencies (P < 0.01 on the 4th day) and improved the spatial memory of the AD mice in the water maze test. Meanwhile, treadmill exercise significantly increased the number of BDNF-positive cells and decreased the ratios of activated microglia in both the cerebral cortex and the hippocampus. However, treadmill exercise did not significantly alleviate the accumulation of β-amyloid in either the cerebral cortex or the hippocampus of the AD mice (P > 0.05). The study suggested that long-term treadmill exercise could improve the spatial memory of the male APPswe/PS1dE9 AD mice. The increase in BDNF-positive cells and decrease in activated microglia might underpin the beneficial effect.     

Electromyography of selected lower-limb muscles fatigued by exercise at the intensity of soccer match-play.

Surface electromyography has been useful in comparing muscular activity among different sports movements and it is a valuable technique for evaluating muscle activation, co-ordination and fatigue. Since these important variables have not been investigated during the full game in soccer, the present study aimed to investigate the activity of major muscles of the lower extremity during a soccer-simulation fatiguing protocol. Ten amateur soccer players (age 21.40+/-3.13 years; height 1.77+/-0.06 m; mass 74.55+/-8.5 kg) were tested. The exercise protocol, performed on a programmable motorised treadmill, consisted of the different intensities observed during soccer match-play (walking, jogging, running, sprinting). Electromyographic activity was recorded from the rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA) and gastrocnemius (GC) muscles before exercise, at half-time and immediately after the 90-min exercise protocol. The EMG data were analysed using custom-written software to compute the root mean square (RMS) value over ten gait cycles. With regard to RF, BF and TA, a significant main effect (P< 0.05) was found for condition (pre-game, half-time and post-game), speed (6, 12, 15 and 21 km h(-1)) (P<0.05) and interaction between condition and speed (P< 0.05). For GC, a significant effect was not found for condition or interaction between condition and speed, but a significant main effect (P< 0.001) was found for speed, with the RMS value increasing continually with increasing speed from 6 to 2 1km h(-1). The results indicated that after a simulation of the exercise intensity of soccer-play the EMG activity in major lower-limb muscles was less than before. This decrease indicated that prolonged intermittent exercise had an effect on muscle activity even when work-rate was sustained.     

Brain Activation Patterns at Exhaustion in Rats That Differ in Inherent Exercise Capacity

In order to further understand the genetic basis for variation in inherent (untrained) exercise capacity, we examined the brains of 32 male rats selectively bred for high or low running capacity (HCR and LCR, respectively). The aim was to characterize the activation patterns of brain regions potentially involved in differences in inherent running capacity between HCR and LCR. Using quantitative in situ hybridization techniques, we measured messenger ribonuclease (mRNA) levels of c-Fos, a marker of neuronal activation, in the brains of HCR and LCR rats after a single bout of acute treadmill running (7.5–15 minutes, 15° slope, 10 m/min) or after treadmill running to exhaustion (15–51 minutes, 15° slope, initial velocity 10 m/min). During verification of trait differences, HCR rats ran six times farther and three times longer prior to exhaustion than LCR rats. Running to exhaustion significantly increased c-Fos mRNA activation of several brain areas in HCR, but LCR failed to show significant elevations of c-Fos mRNA at exhaustion in the majority of areas examined compared to acutely run controls. Results from these studies suggest that there are differences in central c-Fos mRNA expression, and potential brain activation patterns, between HCR and LCR rats during treadmill running to exhaustion and these differences could be involved in the variation in inherent running capacity between lines.     

Autophagic response to a single bout of moderate exercise in murine skeletal muscle

The effect of a single bout of exercise on autopahgy in murine gastrocnemius muscle was investigated. Autophagy is a process for the degradation system of cytoplasmic components, which may help maintain intracellular quality control of cell survival and turnover under normal conditions. The present study investigated the changes of autophagy-related proteins including microtubule-associated protein 1b light chain 3 (LC3), Beclin-1, Atg7 (autophagy-related gene 7), conjugation form of Atg12 to Atg5, lysosome-associated membrane protein (LAMP2a), and muscle-specific RING finger protein-1 (MURF-1) protein level in gastrocnemius muscle after a single bout of treadmill exercise. Mice exercised on a treadmill for 50 min at a speed of 12.3 m/min with a slope of 5°. The animals were sacrificed by cervical dislocation 0, 3, 6, or 12 h after exercise, and muscle samples were collected immediately. Western blot analysis demonstrated that the autophagy marker LC3-II was significantly decreased during the recovery period (3, 6, and 12 h) whereas there was no decrease immediately after exercise (0 h). To identify factors related to this decrease, autophagosome component proteins were examined in murine gastrocnemius muscle. A decrease in Beclin-1, Atg7, and LAMP2a during recovery period was concomitant with the decreased level of LC3-II. Additionally, MuRF-1 expression was significantly increased after a single bout of exercise. This study is the first to demonstrate autophasic related protein expression after a single bout of treadmill exercise and our results suggest that a single bout of treadmill exercise attenuates the autophagic response in murine skeletal muscle.     

Effects of aquaporin 4 deficiency on the expression of spinal PKCα, PKCγ and c-Fos in naloxone-precipitated morphine withdrawal mice

The previous study indicated that aquaporin 4 (AQP4) deficiency attenuated opioid physical dependence. However, the underlying mechanism remains unknown. In the present study, the effects of AQP4 deficiency on the expression of three factors, protein kinase C (PKC) α, PKCγ and c-Fos in the spinal cord, which are known to be concerned with spinal neuronal sensitization and opiate dependence, were investigated in AQP4 knockout mice using Western blotting analysis. It was observed that AQP4 deficiency reduced the score of naloxone-precipitated abstinent jumping after repeated morphine administration compared with wild-type (P < 0.001). Meanwhile, the protein levels of PKCα and c-Fos in the spinal cord of AQP4 knockout mice were significantly higher than those in the wild-type mice; while the expression of PKCγ was decreased remarkably by AQP4 knockout during the withdrawal (P < 0.01). These data suggest that AQP4 deficiency-attenuated morphine withdrawal responses may be partially attributed to the changes in the spinal expression of PKCα, PKCγ or c-Fos.     

Treadmill exercise increases cell proliferation without altering of apoptosis in dentate gyrus of Sprague-Dawley rats

The effects of forced treadmill exercise on cell proliferation and apoptosis in the hippocampal dentate gyrus in Sprague-Dawley rats were investigated. The animals were classified into three groups: the control group, the easy exercise group, and the moderate exercise group. In the control group, rats were left on the treadmill without running for 30 min per day, while rats in the exercise groups were made to run on the treadmill for the same duration. All rats were injected intraperitoneally with 5-bromo-2'-deoxyuridine (BrdU) one-hour prior to exercise once a day for 7 consecutive days beginning at the start of the exercise regimens. Each of the rats was sacrificed 2 h after the last exercise. Both the easy and moderate exercise groups revealed increased number of BrdU-positive cells in the dentate gyrus compared to the control group. The terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay revealed very few apoptotic cells, with no statistically significant differences among the groups. These results showed that treadmill exercise increases cell proliferation without altering of apoptosis in the dentate gyrus of the hippocampus.