Thyroid hormone deficiency affects anxiety-related behaviors and expression of hippocampal glutamate transporters in male congenital hypothyroid rat offspring.

Thyroid hormones are crucial for brain development and their deficiency during fetal and postnatal periods can lead to mood and cognitive disorders. We aimed to examine the consequences of thyroid hormone deficiency on anxiety-related behaviors and protein expression of hippocampal glutamate transporters in congenital hypothyroid male offspring rats. Possible beneficial effects of treadmill exercise have also been examined. Congenital hypothyroidism was induced by adding propylthiouracil (PTU) to drinking water of pregnant Wistar rats from gestational day 6 until the end of the weaning period (postnatal day 28). Next, following 4 weeks of treadmill exercise (5 days per week), anxiety-related behaviors were examined using elevated plus maze (EPM) and light/dark box tests. Thereafter, protein expression of astrocytic (GLAST and GLT-1) and neuronal (EAAC1) glutamate transporters were measured in the hippocampus by immunoblotting. Hypothyroid rats showed decreased anxiety-like behavior, as measured by longer time spent in the open arms of the EPM and in the light area of the light/dark box, compared to control rats. Hypothyroid rats had significantly higher GLAST and GLT-1 and lower EAAC1 protein levels in the hippocampus than did the euthyroid rats. Following exercise, anxiety levels decreased in the euthyroid group while protein expression of EAAC1 increased and returned to normal levels in the hypothyroid group. Our findings indicate that thyroid hormone deficiency was associated with alterations in protein expression of glutamate transporters in the hippocampus. Up-regulation of hippocampal GLAST and GLT-1 could be at least one of the mechanisms associated with the anxiolytic effects of congenital hypothyroidism.

Treadmill exercise promotes bone tissue recovery in rats subjected to high + Gz loads.

INTRODUCTION: High + Gz loads, the gravitational forces experienced by the body in hypergravity environments, can lead to bone loss in pilots and astronauts, posing significant health risks. MATERIALS AND METHODS: To explore the effect of treadmill exercise on bone tissue recovery, a study was conducted on 72 male Wistar rats. These rats were subjected to four weeks of varying levels of periodic high + Gz loads (1G, 8G, 20G) experiments, and were subsequently divided into the treadmill group and the control group. The treadmill group underwent a continuous two-week treadmill experiment, while the control group rested during this period. The mechanical properties, microstructure, and molecular markers of their tibial bone tissue were measured using three-point bending, micro-CT, and PCR. RESULTS: The results showed that treadmill exercise improved the elastic modulus, ultimate deflection, and ultimate load of rat bone tissue. It also increased the number, density, and volume fraction of bone trabeculae, and decreased their separation. Moreover, treadmill exercise enhanced osteogenesis and inhibited osteoclastogenesis. CONCLUSION: This study demonstrates that treadmill exercise can promote the recovery of bone tissue in rats subjected to high + Gz loads, providing a potential countermeasure for bone loss in pilots and astronauts.

Effects of different combinations of mechanical loading intensity, duration, and frequency on the articular cartilage in mice.

BACKGROUND: Understanding how healthy articular cartilage responds to mechanical loading is critical. Moderate mechanical loading has positive effects on the cartilage, such as maintaining cartilage homeostasis. The degree of mechanical loading is determined by a combination of intensity, frequency, and duration; however, the best combination of these parameters for knee cartilage remains unclear. This study aimed to determine which combination of intensity, frequency, and duration provides the best mechanical loading on healthy knee articular cartilage in vitro and in vivo. METHODS AND RESULTS: In this study, 33 male mice were used. Chondrocytes isolated from mouse knee joints were subjected to different cyclic tensile strains (CTSs) and assessed by measuring the expression of cartilage matrix-related genes. Furthermore, the histological characteristics of mouse tibial cartilages were quantified using different treadmill exercises. Chondrocytes and mice were divided into the control group and eight intervention groups: high-intensity, high-frequency, and long-duration; high-intensity, high-frequency, and short-duration; high-intensity, low-frequency, and long-duration; high-intensity, low-frequency, and short-duration; low-intensity, high-frequency, and long-duration; low-intensity, high-frequency, and short-duration; low-intensity, low-frequency, and long-duration; low-intensity, low-frequency, and short-duration. In low-intensity CTSs, chondrocytes showed anabolic responses by altering the mRNA expression of COL2A1 in short durations and SOX9 in long durations. Furthermore, low-intensity, low-frequency, and long-duration treadmill exercises minimized chondrocyte hypertrophy and enhanced aggrecan synthesis in tibial cartilages. CONCLUSION: Low-intensity, low-frequency, and long-duration mechanical loading is the best combination for healthy knee cartilage to maintain homeostasis and activate anabolic responses. Our findings provide a significant scientific basis for exercise and lifestyle instructions.

Hepatic kynurenic acid mediates phosphorylation of Nogo-A in the medial prefrontal cortex to regulate chronic stress-induced anxiety-like behaviors in mice.

Exercise training effectively relieves anxiety disorders via modulating specific brain networks. The role of post-translational modification of proteins in this process, however, has been underappreciated. Here we performed a mouse study in which chronic restraint stress-induced anxiety-like behaviors can be attenuated by 14-day persistent treadmill exercise, in association with dramatic changes of protein phosphorylation patterns in the medial prefrontal cortex (mPFC). In particular, exercise was proposed to modulate the phosphorylation of Nogo-A protein, which drives the ras homolog family member A (RhoA)/ Rho-associated coiled-coil-containing protein kinases 1(ROCK1) signaling cascade. Further mechanistic studies found that liver-derived kynurenic acid (KYNA) can affect the kynurenine metabolism within the mPFC, to modulate this RhoA/ROCK1 pathway for conferring stress resilience. In sum, we proposed that circulating KYNA might mediate stress-induced anxiety-like behaviors via protein phosphorylation modification within the mPFC, and these findings shed more insights for the liver-brain communications in responding to both stress and physical exercise.

Effect of experimental modulation of mood on exertional dyspnoea in chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Dyspnoea is a debilitating symptom in individuals with chronic obstructive pulmonary disease (COPD) and a range of other chronic cardiopulmonary diseases and is often associated with anxiety and depression. The present study examined the effect of visually-induced mood shifts on exertional dyspnoea in individuals with COPD. METHODS: Following familiarization, 20 participants with mild to severe COPD (age 57-79 years) attended three experimental sessions on separate days, performing two 5-min treadmill exercise tests separated by a 30-min interval on each day. During each exercise test, participants viewed either a positive, negative or neutral set of images sourced from the International Affective Picture System (IAPS) and rated dyspnoea or leg fatigue (0-10). Heart rate (HR) and peripheral oxygen saturation (SpO2 ) were measured at 1-min intervals during each test. Mood valence ratings were obtained using Self-Assessment Manikin (SAM) scale (1-9). RESULTS: Mood valence ratings were significantly higher when viewing positive (end-exercise mean ± SEM = 7.6 ± 0.3) compared to negative IAPS images (2.4 ± 0.3, p < 0.001). Dyspnoea intensity (mean ± SEM = 5.8 ± 0.4) and dyspnoea unpleasantness (5.6 ± 0.3) when viewing negative images were significantly higher compared to positive images (4.2 ± 0.4, p = 0.004 and 3.4 ± 0.5, p = 0.003). Eighty-five percent of participants (n = 17) met the minimal clinically important difference (MCID) criteria for both dyspnoea intensity and unpleasantness. HR, SpO2 and leg fatigue did not differ significantly between conditions. CONCLUSION: These findings indicate that the negative affective state worsens dyspnoea in COPD, thereby suggesting strategies aimed at reducing the likelihood of negative mood or improving the mood may be effective in managing morbidity associated with dyspnoea in COPD.

Aerobic exercise training engages the canonical wnt pathway to improve pulmonary function and inflammation in COPD.

BACKGROUND: We studied whether the exercise improves cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD) in mice through inhibition of inflammation mediated by Wnt/ß-catenin-peroxisome proliferator-activated receptor (PPAR) γ signaling. METHODS: Firstly, we observed the effect of exercise on pulmonary inflammation, lung function, and Wnt/ß-catenin-PPARγ. A total of 30 male C57BL/6J mice were divided into the control group (CG), smoke group (SG), low-intensity exercise group (LEG), moderate-intensity exercise group (MEG), and high-intensity exercise group (HEG). All the groups, except for CG, underwent whole-body progressive exposure to CS for 25 weeks. Then, we assessed the maximal exercise capacity of mice from the LEG, MEG, and HEG, and performed an 8-week treadmill exercise intervention. Then, we used LiCl (Wnt/ß-catenin agonist) and XAV939 (Wnt/ß-catenin antagonist) to investigate whether Wnt/ß-catenin-PPARγ pathway played a role in the improvement of COPD via exercise. Male C57BL/6J mice were randomly divided into six groups (n = 6 per group): CG, SG, LiCl group, LiCl and exercise group, XAV939 group, and XAV939 and exercise group. Mice except those in the CG were exposed to CS, and those in the exercise groups were subjected to moderate-intensity exercise training. All the mice were subjected to lung function test, lung histological assessment, and analysis of inflammatory markers in the bronchoalveolar lavage fluid, as well as detection of Wnt1, ß-catenin and PPARγ proteins in the lung tissue. RESULTS: Exercise of various intensities alleviated lung structural changes, pulmonary function and inflammation in COPD, with moderate-intensity exercise exhibiting significant and comprehensive effects on the alleviation of pulmonary inflammation and improvement of lung function. Low-, moderate-, and high-intensity exercise decreased ß-catenin levels and increased those of PPARγ significantly, and only moderate-intensity exercise reduced the level of Wnt1 protein. Moderate-intensity exercise relieved the inflammation aggravated by Wnt agonist. Wnt antagonist combined with moderate-intensity exercise increased the levels of PPARγ, which may explain the highest improvement of pulmonary function observed in this group. CONCLUSIONS: Exercise effectively decreases COPD pulmonary inflammation and improves pulmonary function. The beneficial role of exercise may be exerted through Wnt/ß-catenin-PPARγ pathway.

Simultaneous Treatment of 5-Aminosalicylic Acid and Treadmill Exercise More Effectively Improves Ulcerative Colitis in Mice.

Ulcerative colitis (UC) is characterized by continuous mucosal ulceration of the colon, starting in the rectum. 5-Aminosalicylic acid (5-ASA) is the main therapy for ulcerative colitis; however, it has side effects. Physical exercise effectively increases the number of anti-inflammatory and anti-immune cells in the body. In the current study, the effects of simultaneous treatment of treadmill exercise and 5-ASA were compared with monotherapy with physical exercise or 5-ASA in UC mice. To induce the UC animal model, the mice consumed 2% dextran sulfate sodium dissolved in drinking water for 7 days. The mice in the exercise groups exercised on a treadmill for 1 h once a day for 14 days after UC induction. The 5-ASA-treated groups received 5-ASA by enema injection using a 200 µL polyethylene catheter once a day for 14 days. Simultaneous treatment improved histological damage and increased body weight, colon weight, and colon length, whereas the disease activity index score and collagen deposition were decreased. Simultaneous treatment with treadmill exercise and 5-ASA suppressed pro-inflammatory cytokines and apoptosis following UC. The benefits of this simultaneous treatment may be due to inhibition on nuclear factor-κB/mitogen-activated protein kinase signaling activation. Based on this study, simultaneous treatment of treadmill exercise and 5-ASA can be considered as a new therapy of UC.

Effects of conventional versus virtual reality-simulated treadmill exercise on fatigue, cognitive function, and participant satisfaction in post-COVID-19 subjects. A randomized trial.

Background/objective: Post-COVID-19 subjects typically experience symptoms of fatigue, cognitive impairment, and sleep difficulty, which can be relieved by conventional aerobic exercise. Virtual Reality (VR) technology to support conventional exercise has recently gained much attention. Therefore, this study aimed to assess the effects of traditional treadmill exercise compared to virtual reality-simulated treadmill exercise on fatigue, cognitive function, sleep quality, and participant satisfaction with the exercise program in post-COVID-19 subjects. Methods: This single-centered, randomized, parallel-group intervention study was conducted between December 2021 and March 2022. Sixteen of twenty post-COVID-19 subjects completed this study (n1 = 8, n2 = 8). Inclusion criteria were persistent dyspnea/fatigue, mild cognitive problems, and age from 30-60 years. Exclusion criteria were previous severe COVID-19 infection and ICU admission, concomitant respiratory or cardiovascular disease, and musculoskeletal or neurological disease. Eligible subjects were assigned randomly to two groups: a non-VR group that received traditional treadmill aerobic exercise only and a VR group that received treadmill exercise with non-immersive VR. Both groups received moderate-intensity exercise on a treadmill at [50-60 % (peak HR－resting HR) + resting HR] for 30-45 min, three times per week, and for four weeks. The outcome measures were the Chalder Fatigue Scale, Montreal Cognitive Assessment (MoCA) questionnaire, Pittsburgh Sleep Quality Index (PSQI), and participant satisfaction with the exercise program rated on a 5-point Likert scale. Results: Both groups showed significant improvements in the Chalder Fatigue Scale, the MoCA questionnaire, and the PSQI scores after training compared to baseline (p < 0.05), without significant differences between them (p > 0.05). However, participant satisfaction with the exercise program was significantly higher in the VR group than in the non-VR group (p = 0.037). Conclusion: A moderate-intensity 4-week treadmill exercise program with and without non-immersive VR may improve fatigue, cognitive function, and sleep quality to the same extent in COVID-19 survivors. However, participant satisfaction with the exercise program could be greater after conventional treadmill training assisted by non-immersive VR than after conventional treadmill training alone in this cohort. Trial registration: Pan African Clinical Trials Registry, PACTR202311561948428, retrospectively registered.

Treadmill workout activates PPARα in the hippocampus to upregulate ADAM10, decrease plaques and improve cognitive functions in 5XFAD mouse model of Alzheimer's disease.

Although liver is rich in peroxisome proliferator-activated receptor α (PPARα), recently we have described the presence of PPARα in hippocampus where it is involved in non-amyloidogenic metabolism of amyloid precursor protein (APP) via ADAM10, decreasing amyloid plaques and improving memory and learning. However, mechanisms to upregulate PPARα in vivo in the hippocampus are poorly understood. Regular exercise has multiple beneficial effects on human health and here, we describe the importance of regular mild treadmill exercise in upregulating PPARα in vivo in the hippocampus of 5XFAD mouse model of Alzheimer's disease. We also demonstrate that treadmill exercise remained unable to stimulate ADAM10, reduce plaque pathology and improve cognitive functions in 5XFADΔPPARα mice (5XFAD mice lacking PPARα). On the other hand, treadmill workout increased ADAM10, decreased plaque pathology and protected memory and learning in 5XFADΔPPARß mice (5XFAD mice lacking PPARß). Moreover, the other PPAR (PPARγ) also did not play any role in the transcription of ADAM10 in vivo in the hippocampus of treadmill exercised 5XFAD mice. These results underline an important role of PPARα in which treadmill exercise remains unable to exhibit neuroprotection in the hippocampus in the absence of PPARα.

The Interaction Effect of Sleep Deprivation and Treadmill Exercise in Various Durations on Spatial Memory with Respect to the Oxidative Status of Rats.

Sleep deprivation (SD) has deleterious effects on cognitive functions including learning and memory. However, some studies have shown that SD can improve cognitive functions. Interestingly, treadmill exercise has both impairment and improvement effects on memory function. In this study, we aimed to investigate the effect of SD for 4 (short-term) and 24 (long-term) hours, and two protocols of treadmill exercise (mild short-term and moderate long-term) on spatial memory performance, and oxidative and antioxidant markers in the serum of rats. Morris Water Maze apparatus was used to assess spatial memory performance. Also, SD was done using gentle handling method. In addition, the serum level of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) was measured. The results showed that 24 h SD (but not 4 h) had negative effect on spatial memory performance, decreased SOD, CAT, and GSH-Px level, and increased MDA level. Long-term moderate (but not short-term mild) treadmill exercise had also negative effect on spatial memory performance, decreased SOD, CAT, and GSH-Px level, and increased MDA level. Interestingly, both protocols of treadmill exercise reversed spatial memory impairment and oxidative stress induced by 24 h SD. In conclusion, it seems that SD and treadmill exercise interact with each other, and moderate long-term exercise can reverse the negative effects of long-term SD on memory and oxidative status; although, it disrupted memory function and increased oxidative stress by itself.

Low-intensity pulsed ultrasound enhances the positive effects of high-intensity treadmill exercise on bone in rats.

INTRODUCTION: Moderate exercise benefits bone health, but excessive loading leads to bone fatigue and a decline in mechanical properties. Low-intensity pulsed ultrasound (LIPUS) can stimulate bone formation. The purpose of this study was to explore whether LIPUS could augment the skeletal benefits of high-intensity exercise. MATERIALS AND METHODS: MC3T3-E1 osteoblasts were treated with LIPUS at 80 mW/cm2 or 30 mW/cm2 for 20 min/day. Forty rats were divided into sham treatment normal control (Sham-NC), sham treatment high-intensity exercise (Sham-HIE), 80 mW/cm2 LIPUS (LIPUS80), and high-intensity exercise combined with 80 mW/cm2 LIPUS (LIPUS80-HIE). The rats in HIE group were subjected to 30 m/min slope treadmill exercise for 90 min/day, 6 days/week for 12 weeks. The LIPUS80-HIE rats were irradiated with LIPUS (1 MHz, 80 mW/cm2) for 20 min/day at bilateral hind limb after exercise. RESULTS: LIPUS significantly accelerated the proliferation, differentiation, mineralization, and migration of MC3T3-E1 cells. Compared to 30 mW/cm2 LIPUS, 80 mW/cm2 LIPUS got better promotion effect. 12 weeks of high-intensity exercise significantly reduced the muscle force, which was significantly reversed by LIPUS. Compared with the Sham-NC group, Sham-HIE group significantly optimized bone microstructure and enhanced mechanical properties of femur, and LIPUS80-HIE further enhanced the improvement effect on bone. The mechanisms may be related to activate Wnt/ß-catenin signal pathway and then up-regulate the protein expression of Runx2 and VEGF, the key factors of osteogenesis and angiogenesis. CONCLUSION: LIPUS could augment the skeletal benefits of high-intensity exercise through Wnt/ß-catenin signal pathway.

Evaluation of a new treadmill exercise protocol to unmask type 1 Brugada electrocardiographic pattern: can we improve diagnostic yield?

AIMS: High precordial leads (HPL) on the resting electrocardiogram (ECG) are widely used to improve diagnostic detection of type 1 Brugada ECG pattern (Br1ECGp). A parasympathetic activation marks the initial recovery phase of treadmill stress testing (TET), and this can be useful for detecting the typical ECG pattern. Our study aimed to evaluate the role of a new HPL-treadmill exercise testing (TET) protocol in detecting Br1ECGp fluctuation compared to resting HPL-ECG. METHODS AND RESULTS: 74 out of 163 patients of a Brugada syndrome (BrS) Brazilian cohort (GenBra Registry) underwent exercise testing with HPL-TET protocol. Precordial leads were displayed in strategic positions in the right and left parasternal spaces. The step-by-step analysis included ECG classification (as presence or absence of Br1ECGp) in standard vs. HPL leads placement in the following sequences: resting phase, maximal exercise, and the passive recovery phase (including 'quick lay down'). For heart rate recovery (HRR) measurements and comparisons, a Student's t-test was applied. McNemar tests compared the detection of Br1ECGp. The significance level was defined as P < 0.05. Fifty-seven patients (57/74; 77%) were male, the mean age was 49.0 ± 14, 78.4% had spontaneous BrS, and the mean Shanghai score was 4.5. The HPL-TET protocol increased Br1ECGp detection by 32.4% against resting HPL-ECG (52.7% vs. 20.3%, P = 0.001) alone. CONCLUSION: Stress testing using HPL with the passive recovery phase in the supine position offers an opportunity to unmask the type 1 Br1ECGp, which could increase the diagnostic yield in this population.

Treadmill running and Levisticum Officinale extract protect against LPS-induced memory deficits by modulating neurogenesis, neuroinflammation and oxidative stress.

Neuroinflammation plays an essential role in the pathogenesis of Alzheimer's disease. The preventive effect of physical exercise on attenuating neuroinflammation has not been completely defined. Levisticum officinale is known as a medicinal plant with antioxidant and anti-inflammatory properties. The current study was designed to investigate the neuroprotective impacts of treadmill running and Levisticum officinale on lipopolysaccharide (LPS)-induced learning and memory impairments and neuroinflammation in rats. Male Wistar rats ran on a treadmill and/or were pretreated with Levisticum officinale extract at a dose of 100 mg/kg for a week. Then, rats received intraperitoneal injection of LPS at a dose of 1 mg/kg. Treadmill running and/or treatment of extract lasted three more weeks. Behavioral, molecular, biochemical and immunohistochemical assessments were carried out after the end of the experiment. LPS administration resulted in spatial learning and memory impairments along with increased mRNA expression of interleukin-6 and malondialdehyde levels, as well as decreased superoxide dismutase activity and neurogenesis in the hippocampus. Moreover, treadmill running for four weeks, alone and in combination with Levisticum officinale extract attenuated spatial learning and memory deficits, decreased the mRNA expression of interleukin-6 and malondialdehyde levels, and enhanced superoxide dismutase activity and neurogenesis in the hippocampus. In conclusion, the advantageous effects of running exercise and Levisticum officinale extract on LPS-induced memory impairments are possibly due to the antioxidant and anti-inflammatory activity and enhancing neurogenesis.

Treadmill Exercise Alleviates Cognition Disorder by Activating the FNDC5: Dual Role of Integrin αV/ß5 in Parkinson's Disease.

Parkinson's disease with cognitive impairment (PD-CI) results in several clinical outcomes for which specific treatment is lacking. Although the pathogenesis of PD-CI has not yet been fully elucidated, it is related to neuronal plasticity decline in the hippocampus region. The dopaminergic projections from the substantia nigra to the hippocampus are critical in regulating hippocampal plasticity. Recently, aerobic exercise has been recognized as an effective therapeutic strategy for enhancing plasticity through the secretion of various muscle factors. The exact role of FNDC5-an upregulated, newly identified myokine produced after exercise-in mediating hippocampal plasticity and regional dopaminergic projections in PD-CI remains unclear. In this study, the effect of treadmill exercise on hippocampal synaptic plasticity was evaluated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced chronic PD models. The results showed that treadmill exercise substantially alleviated the motor dysfunction, cognition disorder, and dopaminergic neuron degeneration induced by MPTP. Here, we discovered that the quadriceps, serum, and brain FNDC5 levels were lower in PD mice and that intervention with treadmill exercise restored FNDC5 levels. Moreover, treadmill exercise enhanced the synaptic plasticity of hippocampal pyramidal neurons via increased dopamine levels and BDNF in the PD mice. The direct protective effect of FNDC5 is achieved by promoting the secretion of BDNF in the hippocampal neurons via binding the integrin αVß5 receptor, thereby improving synaptic plasticity. Regarding the indirect protection effect, FNDC5 promotes the dopaminergic connection from the substantia nigra to the hippocampus by mediating the interaction between the integrin αVß5 of the hippocampal neurons and the CD90 molecules on the membrane of dopaminergic terminals. Our findings demonstrated that treadmill exercise could effectively alleviate cognitive disorders via the activation of the FNDC5-BDNF pathway and enhance the dopaminergic synaptic connection from SNpc to the hippocampus in the MPTP-induced chronic PD model.

Study on the Role of MicroRNA-214 in the Rehabilitation of Cartilage in Mice with Exercise-Induced Traumatic Osteoarthritis.

This study aimed to explore the possible relationship between the expression of Micro RNA-214 (miR-214) and the pathogenesis and recovery in mice with post-traumatic osteoarthritis (PTOA). In this study, 40 male C57BL/6 mice were randomly divided into five groups: model control (MC) group, model (M) group, rehabilitation control (RC) group, model + rehabilitation (M + R) group, and model + convalescent (M + C) group. Four weeks of high-intensity treadmill exercise (HITE) and 4 weeks of moderate-intensity treadmill exercise (MITE) were implemented for PTOA modeling and rehabilitation, respectively. In vitro, 10% elongation mechanical strain was used for IL-1ß stimulated chondrocytes. We found that compared with the MC group, there was a significant increase in the aspect of inflammation and catabolism while a dramatic fall in miR-214 expression was observed in the M group. After the 4 weeks of MITE, the level of inflammation and metabolism, as well as miR-214 expression, was partially reversed in the M + R group compared with the M + C group. The expression of miR-214 decreased dramatically after chondrocyte stimulation by IL-1ß and then increased significantly after 10% strain was applied to IL-1ß-treated cells. These results suggest that a suitable mechanical load can increase the expression of miR-214, and that miR-214 may play a chondroprotective effect in the development of OA.

Exercise training counteracts the cardiac metabolic remodelling induced by experimental pulmonary arterial hypertension.

Exercise training provides several cardiovascular benefits in both physiological and pathological conditions; however, its use as a therapeutic tool for pulmonary arterial hypertension (PAH) has been poorly explored. This study aimed to extend the comprehension of the cardioprotective effects of exercise training in the set of PAH focusing on the metabolic changes promoted by exercise in the right ventricle (RV). The monocrotaline animal model of PAH was used and male Wistar rats were submitted to two weeks of treadmill exercise training (5 days/week, 60 min/day, 25 m/min) following disease establishment. Trained rats showed an improved diastolic function (lower end-diastolic pressure and tau) despite the presence of cardiac overload (increased peak systolic pressure, end-diastolic pressure and arterial elastance). This enhanced hemodynamic response was paralleled by an increased uptake of glucose to cardiomyocytes through glucose transporter type 4 (GLUT4) followed by increased lactate dehydrogenase (LDH) activity. Exercise did not reverse the decrease of fatty acid oxidation related to PAH but increased the content of the transcription factors peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Two weeks of exercise did not modulate the changes in amino acid metabolism secondary to PAH. Our work suggests that continuous aerobic exercise of moderate intensity, despite its short-term duration and application in a late stage of the disease, supports the RV response to PAH by promoting a shift in the cardiac metabolic phenotype.

Effects of teriparatide and low-intensity aerobic exercise on osteopenia in type 2 diabetes mellitus rats.

INTRODUCTION: In patients with type 2 diabetes mellitus (T2DM), bone fragility increases fracture risk. Teriparatide (TPTD) improves bone strength, and exercise therapy suppresses blood glucose levels in T2DM. In this study, the combined effects of TPTD and exercise therapy on trabecular and cortical bone were examined in advanced T2DM model rats. MATERIALS AND METHODS: Thirty-week-old Otsuka Long-Evans Tokushima Fatty rats were divided into four groups (n = 9-10 in each group at two time points): Cont group (vehicle-treated control), TPTD group (TPTD 30 µg/kg injected subcutaneously, 3 times/week), Exe group (treadmill exercise, 10 m/min, 60 min/day, 5 times/week), and Comb group (TPTD-treated and treadmill exercise combined). Five and 10 weeks after treatment, bone mineral density (BMD), bone strength, and bone micro-architecture were measured. RESULTS: TPTD and combined treatment significantly increased BMDs of the lumbar spine and femur compared to the Cont group (p < 0.05 to p < 0.01). In the three-point bending test of the femur, only combined treatment increased the maximum load at 5 weeks compared with the Cont and Exe groups (p < 0.01). In the compression test of the distal femoral metaphysis, both TPTD and combined treatment increased the trabecular bone strength compared with the Cont and Exe groups (p < 0.05 to p < 0.01). Although TPTD and combined treatment improved the micro-architecture of trabecular bone (p < 0.05 to p < 0.01), only combined treatment improved the micro-structures of cortical bone from 5 weeks of treatment (p < 0.05 to p < 0.01). CONCLUSION: The combination of TPTD and treadmill exercise increased BMD and trabecular and cortical bone strength of the femur with improved micro-architecture in T2DM model rats.

A single bout of exhaustive treadmill exercise increased AMPK activation associated with enhanced autophagy in mice skeletal muscle.

Previous studies reported inconsistent findings on autophagy activation in skeletal muscles after acute exercise. In this study, we investigated the effect of a single bout of exhaustive treadmill exercise on AMPK and autophagy activations in mice gastrocnemius muscle in vivo. Male ICR/CD-1 mice were randomly divided into the control and exercise groups. The later was subjected to a single bout of exhaustive treadmill exercise. Changes of AMPK, phosphorylation of AMPKThr172 (pAMPKThr172 ), and autophagy markers including Beclin1, LC3II/LC3I and p62 mRNA and protein expressions in gastrocnemius muscle at different times (0, 6, 12, 24 h) after the exercise were analysed by quantitative real-time PCR and western blot. Our results demonstrated that a single bout of exhaustive treadmill exercise significantly induced AMPK content and AMPK activity at 0, 6 and 12 h after the exercise, and changed the expressions of autophagy markers at different time points in the recovery period, respectively. Moreover, we observed positive correlations between expressions of LC3II/LC3I ratio and pAMPKThr172 or AMPK, and a negative correlation between expressions of p62 and AMPK or pAMPKThr172 . In conclusion, a single bout of exhaustive treadmill exercise in mice caused a prolonged activation of AMPK and improved autophagy in the gastrocnemius muscle. The regulation of autophagic markers were related to enhanced AMPK activity. The findings indicate that acute exercise enhanced AMPK-related autophagy activation may be the underlying molecular mechanism that regulates cellular energy metabolism during exercise.

Protective effects of treadmill exercise on apoptotic neuronal damage and astrocyte activation in ovariectomized and/or diabetic rat prefrontal cortex: molecular and histological aspects.

OBJECTIVE: Both estrogen deprivation and diabetes mellitus are known as risk factors for neuronal damage. Using an animal model of ovariectomized and/or streptozotocin (STZ)-induced diabetes mellitus, we examined expression of apoptosis-related proteins, neuronal damage, and astrocyte activation in prefrontal cortex of rats with/without treadmill exercise. METHODS: Adult female Wistar rats were divided into control, ovariectomized (Ovx, bilateral ovariectomy), diabetic (Dia, STZ 60 mg/kg; i.p.), and ovariectomized diabetic (Ovx + Dia) groups. Next, animals in each group were randomly subdivided into non-exercise and exercise subgroups. Animals in the exercise groups underwent moderate treadmill running for 4 weeks (5 days/week). Thereafter, expression of Bax, Bcl-2, and caspase-3, as apoptosis-related proteins, number of neurons, and number of glial fibrillary acidic protein (GFAP)-positive cells in prefrontal cortex were measured using immunoblotting, cresyl violet staining, and immunohistochemistry, respectively. RESULTS: In both Dia and Ovx + Dia groups, Bax and caspase-3 protein levels and number of GFAP-positive cells were higher than those in the control group, while Bcl-2 protein level and number of neurons compared were lower than the control group. Beneficial effects of exercise to prevent apoptosis-mediated neuronal damage and astrocyte activation were also observed in the Dia group. CONCLUSION: Based on our results, physical exercise could be beneficial to attenuate diabetes-induced neuronal damage in the prefrontal cortex via inhibition of apoptosis.

Peak treadmill exercise echocardiography for ischemia detection.

Of the stress echocardiographic methods, exercise should be the first choice for patients able to exercise, according to guidelines. Among ExE modalities, treadmill ExE with acquisition of images at peak exercise has several advantages, including high sensitivity and prognostic value. Overall, sensitivity of ExE is around 80%-85%, although figures for peak imaging on the treadmill are 85%-90%. Despite it, guidelines do not mention this method.