Exercise improves behavioral dysfunction and inhibits the spontaneous excitatory postsynaptic current of D2-medium spiny neurons.

The abnormal function of striatal medium spiny neurons (MSNs) leads to the excitation-inhibition imbalance of the basal ganglia, which is an important pathogenic factor of Parkinson's disease (PD). Exercise improves the dysfunction of basal ganglia through neuroprotective and neuroreparative effects, which may be related to the functional changes of expresses D2 receptors MSNs (D2-MSNs). In this study, D2-Cre mice were selected as the research objects, the PD model was induced by unilateral injection of 6-hydroxydopamine (6-OHDA) in the striatum, and the 4-week treadmill training method was used for exercise intervention. Using optogenetics and behavioral tests, we determined that the average total movement distance of PD and PD + Ex groups was significantly lower than that of the Control group, while that of the PD + Ex and PD + Laser groups was significantly higher than that of the PD group, and the two intervention methods of exercise and optogenetic-stimulation of the D2-MSNs had basically similar effects on improving the autonomic behavior of PD mice. To further investigate the cellular mechanisms, whole-cell patch clamp recordings were carried out on D2-MSNs. We found that exercise decreased the frequency and amplitude of spontaneous excitatory postsynaptic current (sEPSC) and increased the paired-pulse radio of D2-MSNs while leaving basic electrophysiological properties of MSNs unaffected. Combined with behavioral improvement and enhanced D2R protein expression, our findings suggest the inhibited sEPSC of D2-MSNs may contribute to the behavioral improvement after exercise.

Effects of exercise on the cardiovascular function of rats in a sulfur dioxide polluted environment.

The purpose of the study is to further explore the combined effects of exercise and sulfur dioxide (SO2) exposure on the cardiovascular function as well as the underlying mechanisms. Rats were randomly divided into 4 groups: rest group (RG), exercise group (EG), SO2 pollution group (SG) and SO2 pollution + exercise group (SEG). Changes of aortic pressure and left ventricular pressure, Ang II concentration, ACE concentration and ACE activity in rats' myocardial tissue were observed. Compared with RG, the systolic blood pressure, pulse pressure, LVSP, +dp/dtmax and -dp/dtmax of EG increased significantly, diastolic blood pressure, resting heart rate and ACE activity decreased significantly; For rats of SG, 4 weeks SO2 exposure increased LVEDP, Ang II concentration, ACE concentration and ACE activity, decreased the +dp/dtmax and -dp/dtmax; For rats of SEG, the systolic blood pressure, pulse pressure, LVSP, +dp/dtmax and -dp/dtmax decreased significantly, HR, LVEDP, Ang II concentration, ACE concentration and ACE activity increased significantly. Results indicate that, the combination of aerobic exercise and SO2 exposure can aggravate the negative effects of SO2 inhalation on cardiovascular function. Renin-angiotensin system plays an important role in mediating the negative effect of SO2 inhalation.

Exercise Improves Movement by Regulating the Plasticity of Cortical Function in Hemiparkinsonian Rats.

Aberrant cortical spike-local field potential (LFP) coupling leads to abnormal basal ganglia activity, disruption of cortical function, and impaired movement in Parkinson's disease (PD). Here, the primary motor cortex mediated plasticity mechanism underlying behavioral improvement by exercise intervention was investigated. Exercise alleviates motor dysfunction and induces neuroplasticity in PD. In this study, Sprague-Dawley (SD) rats were injected with 6-hydroxydopamine (6-OHDA) to induce unilateral nigrostriatal dopamine depletion. Two weeks later, a 4-week exercise intervention was initiated in the PD + exercise (Ex) group. Multichannel recording technology recorded spikes and LFPs in rat motor cortices, and balanced ability tests evaluated behavioral performance. The balanced ability test showed that the total crossing time/front leg error/input latency time was significantly lower in PD + Ex rats than in PD rats (P < 0.05). Scalograms and LFP power spectra indicated increased beta-range LFP power in lesioned hemispheres, with exercise reducing LFP power spectral density. Spike-triggered LFP waveform averages showed strong phase-locking in PD motor cortex cells, and exercise reduced spike-LFP synchronization. Our results suggest that exercise can suppress overexcitability of LFPs and minimize spike-LFP synchronization in the motor cortex, leading to motor-improving effects in PD.

Evaluation of a rat model of exercise-induced fatigue using treadmill running with progressively increasing load.

The mechanism behind exercise-induced fatigue is a significant topic in the field of sports physiology. Therefore, establishing and evaluating an acute exercise-induced fatigue animal model that explores the limits of the motor system may provide greater insight into these mechanisms. Heart rate is an important quantitative parameter that accurately reflects the immediate change in physical function due to exercise load. And there is likely to be an important correlation between heart rate and behavioral performance. In this study, changes in heart rate and behavioral indexes during exercise-induced fatigue were quantitatively analyzed in rats using heart rate telemetry and video methods respectively. The behavioral indexes were used as independent variables and the degree of fatigue was used as the forecast value. Ternary quadratic function curve fitting was used to deduce a formula to calculate a fatigue score: Y = 15.2548+0.4346∙xa-0.1154∙xb+0.6826∙xc+0.0044∙xa∙xb-0.0021∙xb∙xc-0.0013∙xc∙xa-0.0023∙xa2-0.0016∙xb2 (r2=0.906). It identified a linear relationship between heart rate and exercise intensity, with a plateau in heart rate occurring during difference periods. It will serve as an effective reference for the modeling of exercise-induced fatigue. In addition, it also provides a theoretical method for analyzing the correlation between peripheral and central parameters.

[Dopamine D2 receptor may be involved in the regulation of cortical-striatum synaptic transmission and autonomic activity in PD mice by exercise].

The aim of the present study was to reveal the role of cortical-striatum postsynaptic dopamine D2 receptor (D2R) in improving motor behavioral dysfunction in Parkinson's disease (PD) mice by exercise. C57/BL6 male adult mice were randomly divided into control, PD and PD plus exercise groups. The mice were injected with 6-OHDA in striatum to establish a unilateral injury PD model. The exercise intervention program was uniform speed running (16 m/min, 40 min/d, 5 d per week for 4 weeks). Autonomic activity of mice was tested by open field test. Cortical-striatum synaptic transmission efficiency was assessed by peak amplitude of field excitatory postsynaptic potential (fEPSP) recorded from in vitro brain slides. Meanwhile, the effects of D2R agonist on autonomic activity and cortical-striatal synaptic transmission were observed. The results showed that, compared with PD group, PD plus exercise group exhibited significantly increased autonomic motor distance and proportion of fast-moving (P < 0.05), as well as decreased maximum amplitude of fEPSP under increasing stimulation intensity (0.75-3.00 pA) (P < 0.05) and slope of stimulus-response curve. Compared with PD mice without D2R agonist, the movement distance and rapid movement ratio of PD mice treated with D2R agonist were increased significantly (P < 0.05), whereas fEPSP peak amplitude (P < 0.05) and the slope of stimulus-response curve were decreased. These results indicate that either early exercise intervention or D2R agonist treatment can inhibit the abnormal increase of cortical-striatum synaptic transmission and improve the autonomic motor ability in PD mice, suggesting that the cortical-striatum synaptic D2R may be an important molecular target for exercise to improve the autonomic motor ability of PD mice.

Effects of exercise on mGluR-mediated glutamatergic transmission in the striatum of hemiparkinsonian rats.

Hyperexcitability in the corticostriatal glutamatergic pathway may have a pivotal role in the pathogenesis of Parkinson's disease (PD). Metabotropic glutamate receptors (mGluRs) modulate glutamate transmission by both pre- and postsynaptic mechanisms, making them attractive targets for modifying pathological changes in the corticostriatal pathway. Exercise reportedly alleviates motor dysfunction and induced neuroplasticity in glutamatergic transmission. Here, the mGluR-mediated plasticity mechanism underlying behavioral improvement by exercise intervention was investigated. The experimental models were prepared by 6-hydroxydopamine injection into the right medial forebrain bundle. The models were evaluated with the apomorphine-induced rotation test. Starting 2 weeks postoperatively, exercise intervention was applied to the PD + Ex group for 4 weeks. The exercise-intervention effects on locomotor behavior, glutamate levels, and mGluR (mGluR2/3 and mGluR5) expression in hemiparkinsonian rats were investigated. The results showed that hemiparkinsonian rats have a significant increase in extracellular glutamate levels in the lesioned-lateral striatum. MGluR2/3 protein expression was reduced while mGluR5 protein expression was increased in the striatum. Notably, treadmill exercise markedly reversed these abnormal changes in the corticostriatal glutamate system and promoted motor performance in PD rats. These findings suggest that mGluR-mediated glutamatergic transmission in the corticostriatal pathway may serve as an attractive target for exercise-induced neuroplasticity in hemiparkinsonian rats.

Effects and Mechanism of SO2 Inhalation on Rat Myocardial Collagen Fibers.

BACKGROUND This study investigates the effects and mechanism of sulfur dioxide (SO2) inhalation and exercise on rat myocardial collagen fiber. MATERIAL AND METHODS The rats were randomly divided into 4 groups: a control group (RG), an exercise group (EG), an SO2 pollution group (SRG), and an SO2 pollution and exercise group (SEG). Body weight, cardiac index, and left ventricular index in each group were compared. The myocardial hydroxyproline (Hyp) concentration was determined by pepsin acid hydrolysis. The interstitial myocardial collagen expression was measured by Sirius Red F3B in saturated carbazotic acid. The local myocardial angiotensin II type 1 receptor (AT1R) and connective tissue growth factor (CTGF) expression was tested by immunohistochemistry SABC method. RESULTS Compared with RG, the weight growth rate of EG, SRG, and SEG decreased significantly (P<0.01). Compared with EG, the body weight growth rate of SEG significantly decreased (P<0.01) and cardiac index and left ventricular index decreased but without a significant difference. Compared with EG, myocardial Hyp and collagen concentration, myocardial collagen volume fraction (CVF), perivascular collagen area (PVCA), and the expression of AT1R and CTGF in myocardium of SEG increased significantly (P<0.01). CONCLUSIONS SO2 inhalation and exercise will not only offset beneficial health effects of movement on the cardiovascular system, but also produce more unfavorable influences. People should pay attention to their environment when exercising, and try to avoid exercising in environments with SO2 pollution.

Exercise-Induced Fatigue Impairs Bidirectional Corticostriatal Synaptic Plasticity.

Exercise-induced fatigue (EF) is a ubiquitous phenomenon in sports competition and training. It can impair athletes' motor skill execution and cognition. Corticostriatal synaptic plasticity is considered to be the cellular mechanism of movement control and motor learning. However, the effect of EF on corticostriatal synaptic plasticity remains elusive. In the present study, using field excitatory postsynaptic potential recording, we found that the corticostriatal long-term potentiation (LTP) and long-term depression (LTD) were both impaired in EF mice. To further investigate the cellular mechanisms underlying the impaired synaptic plasticity in corticostriatal pathway, whole-cell patch clamp recordings were carried out on striatal medium spiny neurons (MSNs). MSNs in EF mice exhibited increased spontaneous excitatory postsynaptic current (sEPSC) frequency and decreased paired-pulse ratio (PPR), while with normal basic electrophysiological properties and normal sEPSC amplitude. Furthermore, the N-methyl-D-aspartate (NMDA)/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) ratio of MSNs was reduced in EF mice. These results suggest that the enhanced presynaptic glutamate (Glu) release and downregulated postsynaptic NMDA receptor function lead to the impaired corticostriatal plasticity in EF mice. Taken together, our findings for the first time show that the bidirectional corticostriatal synaptic plasticity is impaired after EF, and suggest that the aberrant corticostriatal synaptic plasticity may be involved in the production and/or maintenance of EF.

Treadmill Exercise Improves Motor Dysfunction and Hyperactivity of the Corticostriatal Glutamatergic Pathway in Rats with 6-OHDA-Induced Parkinson's Disease.

Hyperactivity in the corticostriatal glutamatergic pathway (CGP) induces basal ganglia dysfunction, contributing to parkinsonian syndrome (PS). Physical exercise can improve PS. However, the effect of exercise on the CGP, and whether this pathway is involved in the improvement of PS, remains unclear. Parkinson's disease (PD) was induced in rats by 6-hydroxydopamine injection into the right medial forebrain bundle. Motor function was assessed using the cylinder test. Striatal neuron (SN) spontaneous and evoked firing activity was recorded, and the expression levels of Cav1.3 and CaMKII in the striatum were measured after 4 weeks of treadmill exercise. The motor function in PD rats was improved by treadmill exercise. SN showed significantly enhanced excitability, and treadmill exercise reduced SN excitability in PD rats. In addition, firing activity was evoked in SNs by stimulation of the primary motor cortex, and SNs exhibited significantly decreased stimulus threshold, increased firing rates, and reduced latency. The expression of Cav1.3 and p-CaMKII (Thr286) in the striatum were enhanced in PD rats. However, these effects were reversed by treadmill exercise. These findings suggest that treadmill exercise inhibits CGP hyperactivity in PD rats, which may be related to improvement of PS.

Exercise-Induced Neuroprotection of the Nigrostriatal Dopamine System in Parkinson's Disease.

Epidemiological studies indicate that physical activity and exercise may reduce the risk of developing Parkinson's disease (PD), and clinical observations suggest that physical exercise can reduce the motor symptoms in PD patients. In experimental animals, a profound observation is that exercise of appropriate timing, duration, and intensity can reduce toxin-induced lesion of the nigrostriatal dopamine (DA) system in animal PD models, although negative results have also been reported, potentially due to inappropriate timing and intensity of the exercise regimen. Exercise may also minimize DA denervation-induced medium spiny neuron (MSN) dendritic atrophy and other abnormalities such as enlarged corticostriatal synapse and abnormal MSN excitability and spiking activity. Taken together, epidemiological studies, clinical observations, and animal research indicate that appropriately dosed physical activity and exercise may not only reduce the risk of developing PD in vulnerable populations but also benefit PD patients by potentially protecting the residual DA neurons or directly restoring the dysfunctional cortico-basal ganglia motor control circuit, and these benefits may be mediated by exercise-triggered production of endogenous neuroprotective molecules such as neurotrophic factors. Thus, exercise is a universally available, side effect-free medicine that should be prescribed to vulnerable populations as a preventive measure and to PD patients as a component of treatment. Future research needs to establish standardized exercise protocols that can reliably induce DA neuron protection, enabling the delineation of the underlying cellular and molecular mechanisms that in turn can maximize exercise-induced neuroprotection and neurorestoration in animal PD models and eventually in PD patients.

[Dynamic changes of 'substantianigra-ventralislateralis-cortex' pathway neural activity coherence and neurotransmitters in rat during exhausting exercise].

OBJECTIVE: To reveal the possible mechanism of changes of 'substantianigra-ventralislateralis-cortex' pathway neural activity during one bout of exhausting exercise through observing the neural activity coherence between different nucleus and the concentration of extra-cellular glutamate (Glu) and gamma-aminobutyric acid (GABA). METHODS: Male Wistar rats were randomly divided into neural activity real-time observation group, substantianigra (SNr) extracellular neurotransmitters observation group, ventralislateralis (VL) extracellular neuro-transmitters observation group and supplementary motor area (SMA) extracellular neurotransmitters observation group, 10 rats in each group. For rats of neural activity real-time observation group, by using LFPs and ECoG recording technique, and self-comparison, we simultaneously recorded the dynamic changes of neural activity of rat SNr, VL and SMA during one bout of exhausting exercise. The dynamic changes of ex-tracellular Glu and GABA in rat SNr, VL and SMA were also observed through microdialysis combined high performance liquid chromatography (HPLC) technique and self-comparison method. RESULTS: Based on the behavioral performance, the exhausting exercise process could be di-vided into 5 different stages, the rest condition, auto exercise period, early fatigue period, exhaustion condition and recovery period. The elec-trophysiological study results showed that, the coherence between neural activity in rat SNr, VL and SMA was significant between 0~30 Hz during all the procedure of exhausting exercise. Compared with the rest condition, the microdialysis study showed that the Glu concentrations and Glu/GABA ratio in SNr were decreased significantly during automatic exercise period (P < 0.05, P < 0.01), the GABA concentrations were increased significantly (P < 0.05, P < 0.01), while, in VL and cortex, the Glu concentrations and Glu/GABA ratio were increased significantly (P < 0.05, P < 0.01), the GABA concentrations were decreased significantly (P < 0.05, P < 0.01). Under early fatigue and ex-haustion conditions, compared with the rest condition,the Glu concentrations and Glu/GABA ratio in SNr were increased significantly (P < 0.05, P < 0.01), the GABA concentrations were decreased significantly (P < 0.05, P < 0.01), while the Glu concentrations and Glu/GABA ratio in VL and cortex were decreased significantly (P < 0.05, P < 0.01), the GABA concentrations were increased significantly (P < 0.05, P < 0.01). CONCLUSIONS: The neural net work communication between 'substantianigra-ventralislateralis-cortex' pathway exists, changes of Glu and GABA in the nucelus of the pathway are one of the factors resulting in the changes of neural activity.

Effects of Treadmill Exercise on Spontaneous Firing Activities of Striatal Neurons in a Rat Model of Parkinson's Disease.

Exercise improves motor deficits in Parkinson's disease (PD) patients but the underlying neuronal mechanism is poorly understood. Since the striatum is critical to motor function, we have investigated the potential effects of exercise on the spiking activity of the striatal neurons in a rat model of Parkinson's disease. Twenty-four hours after injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, rats in exercise groups were trained to exercise on a treadmill. Twenty-eight days after 6-OHDA lesion, apomorphine induced fewer rotations in the PD rats with exercise than in PD + Ex rats. Anatomical examination indicates that compared with the PD rats, PD + Ex rats had an attenuated loss of dopamine axonal fibers in the striatum and dopamine neurons in the substantia nigra pars. Equally important, the abnormal burst firing and firing rates in striatal neurons were lower in the PD + Ex rats than in the PD rats. Taken together, our results suggest that exercise has neuroprotective effects that can reduce the degeneration of the nigrostriatal dopamine system and minimize the abnormal neuronal spike firing in parkinsonian striatum, potentially contributing to exercise's motor-improving effects in PD.

Applying (1)H NMR Spectroscopy to Detect Changes in the Urinary Metabolite Levels of Chinese Half-Pipe Snowboarders after Different Exercises.

Monitoring physical training is important for the health and performance of athletes, and real-time assessment of fatigue is crucial to improve training efficiency. The relationship between key biomarkers and exercise has been reported. The aim of this study was to determine the effects of different levels of training exercises on the urine metabolome. (1)H NMR-based metabolomics analysis was performed on urine samples from half-pipe snowboarders, and spectral profiles were subjected to PCA and PLS-DA. Our results show that metabolic profiles varied during different stages of exercises. Lactate, alanine, trimethylamine, malonate, taurine, and glycine levels decreased while TMAO and phenylalanine levels increased in the stage with higher amount and intensity of exercise. Although the amount of exercise was reduced in subsequent stage, no significant variations of metabolic profile were found. Metabolic changes induced by training level were analyzed with related metabolic pathway. Studying metabolome changes can provide a better understanding of the physiology of athletes and could aid in adjusting training.

Modulatory effect of subthalamic nucleus on the development of fatigue during exhausting exercise: an in vivo electrophysiological and microdialysis study in rats.

The purpose of the study was to investigate the modulatory effect of changes of subthalamic nucleus (STN) activity on the development of central fatigue during exhausting exercise, and reveal the possible mechanism that might affect STN activity from the perspective of neurotransmitters. Rats were randomly divided into electrophysiology and microdialysis study groups. For electrophysiological study, electrical activity in sensorimotor cortex and STN were simultaneously recorded before, during and 90min after the exhausting exercise. For microdialysis study, extracellular fluid of STN was continuously collected with a microdialysis probe and glutamate (Glu), gamma-aminobutyric acid (GABA) levels were subsequently detected with high performance liquid chromatography (HPLC). The behavioral studies showed that rats ran well initiatively with the treadmill exercise in the beginning, 45 ± 11.5min later, movement capacity reduced obviously (which was termed as 'early fatigue'). Correspondingly, STN activity increased significantly compared with rest condition (p < 0.05), while, cortex activity decreased significantly (p < 0.05). Subsequently, rats continued their exercise with minor external stimulation till exhaustion. Cortex activity reached the minimum value under exhaustion condition, while STN activity changed insignificantly (p > 0.05). For microdialysis study, the dynamic change of Glu/GABA ratio was consistent with the change of STN activity during the development of 'early fatigue' rather than the development of exhaustion. In conclusion, the present study shows that, the development of the cortex fatigue during exhausting exercise consists of two phases, 'early fatigue' and exhaustion. Our results suggest that, dynamic changes of STN activity are closely relevant to the development of 'early fatigue' rather than exhaustion, and the changes of STN activity during the development of 'early fatigue' might be partly related to the variance of Glu and GABA levels in STN extracellular fluid. Key pointsThe development of the cortex fatigue during exhausting exercise consists of two phases, 'early fatigue' and exhaustion.Dynamic changes of STN activity are closely relevant to the development of 'early fatigue' rather than exhaustion.The changes of STN activity during the development of 'early fatigue' might be partly related to the variance of Glu and GABA levels in STN extracellular fluid.

[Changes of subthalamic nucleus and cortex activity in rat during exhausting exercise].

OBJECTIVE: To observe the modulatory effect of subthalamic nucleus (STN) on activity of motor cortex during exhausting exercise. METHODS: Electrocorticogram (ECoG) and local field potentials (LFPs) recording techniques were applied simultaneously to observe the dynamic changes of oscillations in sensorimotor area and STN of rat during exhausting exercise. RESULTS: Rats ran well initiatively with treadmill at the beginning of the exercise, about 45 min (45 +/- 11.5) later, movement capacity reduced. Corresponding electrical property showed that STN activity increased significantly while activity of cortex decreased significantly. Subsequently rats continued exercise with minor external stimulation utill exhaustion. Activity of ECoG reached the minimum under exhausting stations (P < 0.01), while the activity of LFPs changed insignificantly (P > 0.05). CONCLUSION: During the exhausting exercise, the cortex activity was extensively depressed with the development of fatigue, while the activity of STN increased significantly at the early stage of fatigue, STN took part in the modulation of central fatigue through negative induction. And the increase of STN activity may be one of the key measures accounting for protective inhibition.

[Dynamic changes of 5-HT, DA and their metabolin in rat striatum during exhaustive exercise and recovery].

OBJECTIVE: To study the dynamic characteristics of serotonin (5-HT), dopamine (DA) and their metabolin changes in brain during the development of exercise-induced central fatigue. METHODS: Coupling of microdialysis and capillary electrophoresis-laser induced fluorescence detection method were used to continuously monitored the changes of DA, tryptophan (Trp), tyrosine (Tyr), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in striatum extracellular fluid during the exhaustive exercise and recovery time. RESULTS: The concentrations of Trp, 5-HT, 5-HIAA in striatum extracellular fluid had no remarkable changes in the early time of exercise (P < 0.05), while they significantly increased during the later time of exercise and whole recovery time (P < 0.05, P < 0.01). The concentrations of DA and Tyr significantly increased over basal level in the later exercise time, exhaust and recovery time (P < 0.05, P < 0.01). DA/5-HT significantly increased in the initial time of exercise (P < 0.05, P < 0.01), while decreased during the later exercise time, the nadir occurred at 15 minutes before rats exhausted. DA/5-HT slightly recovered back to basal level during the recovery time, and there was no significant difference during later exercise, exhausted and recovery time compared with basal level (P < 0.05). CONCLUSION: The changes of DA and 5-HT in striatum have phase characteristics. Both of them significantly increase during the development of exercise-induced fatigue. However, the 5-HT plays the dominant role in the dynamic changes of them.