Moderate-intensity Treadmill Exercise Research Articles

A057: Effects of Aerobic Exercise on Glutamate Homeostasis in NAC During Withdrawal Period of Nicotine Addiction

Background/Purpose: The disturbed glutamate homeostasis in the nucleus accumbens (NAc) plays a key role in the induction of relapse during nicotine withdrawal. The uptake of excessive extracellular glutamate relies on astrocytic glutamate transporter-1 (GLT-1) and transporter for cysteine (x-CT). Nicotine abuse leads to decreases in expressions of GLT-1 and xCT in NAc. The purpose of this study was to explore the effects of exercise on the expressions of GLT-1 and x-CT during nicotine withdrawal. Method: (1) 2-month-old male C57BL/6J mice were used in this experiment. Mice were randomly divided into four groups: saline sedentary (SS) group, saline exercise (SE) group, nicotine sedentary (NS) group, and nicotine exercise (NE) group. After the establishment of nicotine addiction model with conditioned place preference (CPP) behavioral paradigm, SE and NE group mice were subjected to moderate intensity treadmill exercise. SS and NS group mice were not given exercise intervention. (2) Exercise program: the first 10min running speed is 12m/min, the last 50min is 15m/min, the slope is 0,60 min/day, 5 days/week, 2 weeks. (3) The nicotine dependence during withdrawal was tested using CPP. (4) The expression of GLT-1 and x-CT in NAc were detected by western blot. (5) The results were expressed as mean ± standard error. Two-way analysis of variance was performed. P < 0.05 was statistically significant. Results: (1) After the establishment of nicotine addiction, CPP scores of NS and NE groups were higher than those in SS group (P < 0.001). After two weeks of aerobic exercise, CPP score of NE group was lower than that in NS group (P < 0.05). (2) GLT-1 expression in NS group was lower compared with SS group (P < 0.05). GLT-1 expression in NE group was higher compared with NS group (P < 0.05). (3) x-CT expression in NS group was lower compared with SS group (P < 0.05). x-CT expression in NE group was higher compared with NS group (P < 0.01). Conclusion/Discussion: The expressions of GLT-1 and x-CT in the NAc are lower, which might be one of the mechanisms of nicotine relapse during withdrawal. Aerobic exercise increases the expression of GLT-1 and x-CT in the NAc from nicotine withdrawal mice, which might be one of the mechanisms of exercise-induced reduction of nicotine relapse during withdrawal.

The effect of an acute bout of exercise on circulating vitamin D metabolite concentrations: a randomised crossover study in healthy adults.

The effect of acute exercise on circulating concentrations of vitamin D metabolites is unclear. To address this knowledge gap, we examined the effect of a bout of treadmill-based exercise versus rest on circulating concentrations of 25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3, 24,25(OH)2D3, 1,25(OH)2D3, and vitamin D2 and D3 in healthy men and women. Thirty-three healthy adults (14 females, 41 (15) years, body mass index 26.2 (3.7) kg/m2, 36.2 (9.2) ml/kg/min; mean (SD)) completed two laboratory visits involving 60min of moderate-intensity treadmill exercise (60% ) versus 60min of seated rest, both in an overnight fasted-state, as part of a randomised crossover design. Venous blood samples were drawn at baseline, immediately (0h), 1h and 24h after the exercise or rest-period. There was a significant time × trial interaction effect for total circulating 25(OH)D (P=0.0148), 25(OH)D3 (P=0.0127) and 1,25(OH)2D3 (P=0.0226). Immediately post-exercise, 25(OH)D, 25(OH)D3 and 1,25(OH)2D3 concentrations were significantly elevated compared to the control resting condition, and 1,25(OH) 2D3 remained significantly elevated 1 h later. Circulating albumin, vitamin D binding protein, calcium and parathyroid hormone were elevated immediately post-exercise. Thus, an acute bout of moderate intensity exercise transiently increases concentrations of circulating 25(OH)D and 1,25(OH)2D3 compared to resting conditions. KEY POINTS: Observational studies suggest that acute exercise might change circulating concentrations of vitamin D metabolites, but this has not been investigated using randomised crossover studies and using robust analytical procedures. In this study, we used a randomised crossover design to examine the effect of a bout of treadmill-based exercise (vs. rest) on circulating concentrations of a wide range of vitamin D metabolites in healthy humans. We show that an acute bout of moderate intensity exercise transiently increases concentrations of circulating 25(OH)D and 1,25(OH)2D3 compared to resting conditions. These findings indicate that regular exercise could lead to transient but regular windows of enhanced vitamin D biological action.

Impact of low-to moderate-intensity exercise training on the mRNA expression of purine receptors across various vessels in SHR.

In this study, we developed an exercise training protocol for assessing both blood pressure dynamics and mRNA expression levels of purine receptors in various vascular tissues during physical activity. The objective is to assess the impact of exercise training on blood pressure regulation in spontaneously hypertensive rats (SHR) and purine receptors in vascular tissues. Wistar Kyoto (WKY) and SHR rats were randomly allocated into sedentary (Sed) and exercise training (ExT) groups. Rats in the Sed groups were allowed unrestricted movement, whereas those in the ExT groups underwent a 16-week regimen of low- to moderate-intensity treadmill exercise. Throughout the intervention period, blood pressure measurements and body weight recordings were conducted. Additionally, mRNA expressions of purine receptors P2X1, P2Y1, and P2Y2 in renal artery (RA), internal carotid artery (Int), thoracic aorta (Aor), and caudal artery (Cau) tissues were assessed. In the Sed group, body weight of SHR rats was observed to be lower compared to the three other groups. Over the course of the exercise regimen, blood pressure in the ExT group of SHR rats reduced gradually, converging towards levels similar to those observed in WKY rats by the conclusion of the exercise period. Regarding mRNA expression patterns of P2X1 receptors across the four blood vessels, WKY and SHR rats demonstrated similar sequences, consistently displaying the highest expression levels in the Cau. Conversely, mRNA expressions of P2Y1 and P2Y2 receptors exhibited distinct sequences across the four blood vessels in both WKY and SHR rats. Notably, compared to the Sed group of WKY rats, mRNA expression of P2X1 receptor in the Int of SHR rats revealed an increase, while expressions in the Aor of WKY rats and the Cau of SHR rats decreased following exercise. Expression of P2Y1 receptor mRNA decreased across all four types of blood vessels in SHR rats. Post-exercise, P2Y1 receptor mRNA expression increased in the Aor, decreased in the Cau of WKY rats, and increased in the Int and renal artery (RA) of SHR rats. Conversely, expressions of P2Y2 receptor mRNA decreased in the Int and Aor of SHR rats. Except for the Aor of WKY rats, expressions of P2Y2 receptor mRNA increased in the other arteries of both rat types following exercise. Differences in the distribution of purine receptor subtypes among distinct arterial segments in both WKY and SHR rats were observed. Exercise training was found to enhance mRNA expression levels of P2Y receptors in these rat models. This finding implies that exercise training might reduce hypertension in SHR rats by bolstering the purinergic relaxation response.

Moderate-Intensity Treadmill Exercise Regulates GSK3α/β Activity in the Cortex and Hippocampus of APP/PS1 Transgenic Mice.

Physical exercise has been shown to be beneficial for individuals with Alzheimer's disease (AD), although the underlying mechanisms are not fully understood. Six-month-old Amyloid precursor protein/Presenilin 1 (APP/PS1) transgenic (Tg) mice and wild-type (Wt) mice were randomly assigned to either a sedentary group (Tg-Sed, Wt-Sed) or an exercise group (Tg-Ex, Wt-Ex) undertaking a 12-week, moderate-intensity treadmill running program. Consequently, all mice were tested for memory function and amyloid β (Aβ) levels and phosphorylation of tau and protein kinase B (Akt)/glycogen synthase kinase-3 (GSK3) were examined in tissues of both the cortex and hippocampus. Tg-Sed mice had severely impaired memory, higher levels of Aβ, and increased phosphorylation of tau, GSK3α tyrosine279, and GSK3β tyrosine216, but less phosphorylation of GSK3α serine21, GSK3β serine9, and Akt serine473 in both tissues than Wt-Sed mice in respective tissues. Tg-Ex mice showed significant improvement in memory function along with lower levels of Aβ and less phosphorylation of tau (both tissues), GSK3α tyrosine279 (both tissues), and GSK3β tyrosine216 (hippocampus only), but increased phosphorylation of GSK3α serine21 (both tissues), GSK3β serine9 (hippocampus only), and Akt serine473 (both tissues) compared with Tg-Sed mice in respective tissues. Moderate-intensity aerobic exercise is highly effective in improving memory function in 9-month-old APP/PS1 mice, most likely through differential modulation of GSK3α/β phosphorylation in the cortex and hippocampus.

Preconditioning by Moderate-Intensity Exercise Prevents Gentamicin-Induced Acute Kidney Injury.

A strict correlation among proximal tubule epithelial cell dysfunction, proteinuria, and modulation of the Renin-Angiotensin System and Kalikrein-Kinin System are crucial factors in the pathogenesis of Acute Kidney Injury (AKI). In this study, we investigated the potential protective effect of preconditioning by moderate-intensity aerobic exercise on gentamicin-induced AKI. Male Wistar rats were submitted to a moderate-intensity treadmill exercise protocol for 8 weeks, and then injected with 80 mg/kg/day s.c. gentamicin for 5 consecutive days. Four groups were generated: 1) NT+SAL (control); 2) NT+AKI (non-trained with AKI); 3) T+SAL (trained); and 4) T+AKI (trained with AKI). The NT+AKI group presented: 1) impairment in glomerular function parameters; 2) increased fractional excretion of Na + , K + , and water; 4) proteinuria and increased urinary γ-glutamyl transferase activity (a marker of tubular injury) accompanied by acute tubular necrosis; 5) an increased renal angiotensin-converting enzyme and bradykinin B1 receptor mRNA expression. Interestingly, the preconditioning by moderate-intensity aerobic exercise attenuated all alterations observed in gentamicin-induced AKI (T+AKI group). Taken together, our results show that the preconditioning by moderate-intensity aerobic exercise ameliorates the development of gentamicin-induced AKI. Our findings help to expand the current knowledge regarding the effect of physical exercise on kidneys during physiological and pathological conditions.

Exercise promotes osteogenic differentiation by activating the long non-coding RNA H19/microRNA-149 axis

BACKGROUND Regular physical activity during childhood and adolescence is beneficial to bone development, as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation. AIM To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying mechanisms. METHODS 20 growing mice were randomly divided into two groups: Con group (control group, n = 10) and Ex group (treadmill exercise group, n = 10). Hematoxylin-eosin staining, immunohistochemistry, and micro-CT scanning were used to assess the bone formation-related indexes of the mouse femur. Bioinformatics analysis was used to find potential miRNAs targets of long non-coding RNA H19 (lncRNA H19). RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic differentiation. RESULTS Compared with the Con group, the expression of bone morphogenetic protein 2 was also significantly increased. The micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density, bone volume fraction, and the number of trabeculae, and decreased trabecular segregation in the femur of mice. Inhibition of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic differentiation. In addition, knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers, which is consistent with the results of autophagy-related protein changes detected in mouse femurs by immunofluorescence. CONCLUSION Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice, thus enhancing the peak bone mass of mice. The lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.

Lipoxin A4 ameliorates knee osteoarthritis progression in rats by antagonizing ferroptosis through activation of the ESR2/LPAR3/Nrf2 axis in synovial fibroblast-like synoviocytes

BackgroundOur previous studies have shown that lipoxin A4 (LXA4) can serve as a potential biomarker for assessing the efficacy of exercise therapy in knee osteoarthritis (KOA), and fibroblast-like synoviocytes (FLSs) may play a crucial role in KOA pain as well as in the progression of the pathology. ObjectiveBy analyzing the GSE29746 dataset and collecting synovial samples from patients with different Kellgren–Lawrence (KL) grades for validation, we focused on exploring the potential effect of LXA4 on ferroptosis in FLSs through the ESR2/LPAR3/Nrf2 axis to alleviate pain and pathological advancement in KOA. MethodsThe association between FLSs ferroptosis and chondrocyte matrix degradation was explored by cell co-culture. We overexpressed and knocked down LPAR3 in vitro to explore its potential mechanism in FLSs. A rat model of monosodium iodoacetate (MIA)-induced KOA was constructed and intervened with moderate-intensity treadmill exercise and intraperitoneal injection of PHTPP to investigate the effects of the LXA4 intracellular receptor ESR2 on exercise therapy. ResultsESR2, LPAR3, and GPX4 levels in the synovium decreased with increasing KL grade. After LXA4 intervention in the co-culture system, GPX4, LPAR3, and ESR2 were upregulated in FLSs, collagen II was upregulated in chondrocytes, and MMP3 and ADAM9 were downregulated. LPAR3 overexpression upregulated the expression of GPX4, Nrf2, and SOD1 in FLSs, while downregulating the expression of MMP13 and MMP3; LPAR3 knockdown reversed these changes. Moderate-intensity platform training improved the behavioral manifestations of pain in KOA rats, whereas PHTPP treatment partially reversed the improvement in synovial and cartilage pathologies induced by platform training. ConclusionLXA4 inhibited FLSs ferroptosis by activating the ESR2/LPAR3/Nrf2 axis, thereby alleviating the pain and pathological progression of KOA. This study brings a new target for the treatment of KOA and also leads to a deeper understanding of the potential mechanisms of exercise therapy for KOA.

No difference in fat oxidation, postexercise energy expenditure or energy intake following ingestion of a protein-based breakfast compared to carbohydrate breakfast.

Background: Manipulation of macronutrient intake and exercise can alter overall energy consumption and potentially body composition. Aim: The purpose of this study was to manipulate the macronutrient content of breakfast before exercise to investigate the impact on exercise energy expenditure and postexercise energy intake (EI). Methods: Twelve active men were recruited, 11 finished the study protocol (age: 28 ± 9 years; VO2max: 56 ± 5 ml·kg-1·min-1). In a randomized crossover design, each participant completed 4 trials, 3 consisting of a specific breakfast (protein, PRO; carbohydrate, CHO; noncaloric; NON-CAL) followed in 1 h by a 45 minutes moderate intensity treadmill exercise protocol. The fourth trial consisted of breakfast and no exercise (CON). An ad-libitum lunch and food for the rest of the day were provided and assessed for EI. Measures included resting metabolic rate pre- and postbreakfast along with oxygen uptake (VO2) during and after exercise, along with hunger scales, and blood measures of glucose, insulin and plasma-PYY prebreakfast, pre-exercise, postexercise, and 60 minutes postexercise. Results: Fat oxidation was highest during exercise in the NON-CAL (0.57 g·min-1) trial with similar levels of fat oxidation between PRO (0.50 g·min-1) and CHO trials (0.48 g·min-1). Hunger was not affected by PRO intake or exercise, nor was appetite hormones and glucose. EI at lunch and dinner was not significantly different between trials. Conclusion: Pre-exercise PRO intake did not modify fat oxidation during exercise, did not lead to a larger VO2 versus CHO, nor did it attenuate EI postexercise.

Treadmill has a more beneficial effect than cycling on fat loss through myokines secretion in obese women

Obesity is a condition characterized by the excessive accumulation of body fat beyond normal limits. Irisin and IL-6 are myokines that have a function to convert white adipose tissue into brown adipose tissue, resulting in thermogenesis that induces energy expenditure and has implications for reducing excess fat accumulation. This study aims to demonstrate the response of moderate-intensity treadmill and ergo cycle exercise on fat loss and increasing myokines secretion in obese adolescent females. A total of 30 obese women met the criteria with body mass index (BMI) of 30.02±2.97 kg/m2, age 21.27±1.31 years were recruited into the study and given single session of aerobic ergo cycle exercise (AEEG) and aerobic treadmill exercise (ATEG) during 45 min. Measurement of myokines, i.e., irisin and IL-6, using Enzyme-Linked Immunosorbent Assay (ELISA) on all samples. Statistical analysis was performed using a one-way ANOVA test and Tukey's HSD post hoc test with significance at the 5% level. The results showed that the average levels of irisin post-exercise were 72.82±42.96 ng/mL at CTLG, 282.50±75.96 ng/mL at AEEG, 488.14±61.30 ng/mL at ATEG, and p = 0.000. Average levels of IL-6 post-exercise were 51.09±15.68 pg/mL at CTLG, 58.94±3.62 pg/mL at AEEG, 129.29±52.65 pg/mL at ATEG, and p = 0.000. Average ∆ FAT were -0.02±0.34 % at CTLG, -0.35±0.19 % at AEEG, -0.46±0.18 pg/mL at ATEG, and p = 0.002. Both intervention of exercise consistently increased irisin levels, while IL-6 levels were found to increase only with aerobic treadmill exercise. Likewise, body fat only decreased after one session of treadmill aerobic exercise compared to ergo cycle aerobic exercise. Keywords: Aerobic exercise, interleukin 6, irisin, obesity, metabolism

Lung transcriptomics reveals the underlying mechanism by which aerobic training enhances pulmonary function in chronic obstructive pulmonary disease

BackgroundAerobic training is the primary method of rehabilitation for improving respiratory function in patients with chronic obstructive pulmonary disease (COPD) in remission. However, the mechanism underlying this improvement is not yet fully understood. The use of transcriptomics in rehabilitation medicine offers a promising strategy for uncovering the ways in which exercise training improves respiratory dysfunction in COPD patients. In this study, lung tissue was analyzed using transcriptomics to investigate the relationship between exercise and lung changes.MethodsMice were exposed to cigarette smoke for 24 weeks, followed by nine weeks of moderate-intensity treadmill exercise, with a control group for comparison. Pulmonary function and structure were assessed at the end of the intervention and RNA sequencing was performed on the lung tissue.ResultsExercise training was found to improve airway resistance and lung ventilation indices in individuals exposed to cigarette smoke. However, the effect of this treatment on damaged alveoli was weak. The pair-to-pair comparison revealed numerous differentially expressed genes, that were closely linked to inflammation and metabolism.ConclusionsFurther research is necessary to confirm the cause-and-effect relationship between the identified biomarkers and the improvement in pulmonary function, as this was not examined in the present study.

Moderate mechanical stress suppresses chondrocyte ferroptosis in osteoarthritis by regulating NF-κB p65/GPX4 signaling pathway

Ferroptosis is a recently identified form of programmed cell death that plays an important role in the pathophysiological process of osteoarthritis (OA). Herein, we investigated the protective effect of moderate mechanical stress on chondrocyte ferroptosis and further revealed the internal molecular mechanism. Intra-articular injection of sodium iodoacetate (MIA) was conducted to induce the rat model of OA in vivo, meanwhile, interleukin-1 beta (IL-1β) was treated to chondrocytes to induce the OA cell model in vitro. The OA phenotype was analyzed by histology and microcomputed tomography, the ferroptosis was analyzed by transmission electron microscope and immunofluorescence. The expression of ferroptosis and cartilage metabolism-related factors was analyzed by immunohistochemical and Western blot. Animal experiments revealed that moderate-intensity treadmill exercise could effectively reduce chondrocyte ferroptosis and cartilage matrix degradation in MIA-induced OA rats. Cell experiments showed that 4-h cyclic tensile strain intervention could activate Nrf2 and inhibit the NF-κB signaling pathway, increase the expression of Col2a1, GPX4, and SLC7A11, decrease the expression of MMP13 and P53, thereby restraining IL-1β-induced chondrocyte ferroptosis and degeneration. Inhibition of NF-κB signaling pathway relieved the chondrocyte ferroptosis and degeneration. Meanwhile, overexpression of NF-κB by recombinant lentivirus reversed the positive effect of CTS on chondrocytes. Moderate mechanical stress could activate the Nrf2 antioxidant system, inhibit the NF-κB p65 signaling pathway, and inhibit chondrocyte ferroptosis and cartilage matrix degradation by regulating P53, SLC7A11, and GPX4.

Mechanical strain regulates osteogenesis via Antxr1/LncRNA H19/Wnt/β-catenin axis.

Alleviating bone loss is an essential way to prevent osteoporotic fractures. Proper exercise improves bone density without the side effects of long-term medications, but the mechanism is unclear. Our study explored the role of Antxr1/LncRNA H19/Wnt/β-catenin axis in the process of exercise-mediated alleviation of bone loss. Here we discovered that moderate-intensity treadmill exercise alleviates bone loss caused by ovariectomy and ameliorates bone strength accompanied by an increased lncRNA H19 expression. Concomitantly, Antxr1, a mechanosensitive protein was found downregulated by exercise but upregulated by ovariectomy. Interestingly, knockdown expression of Antxr1 increased lncRNA H19 expression and Wnt/β-catenin signaling pathway in bone marrow mesenchymal stem cells,whereas overexpression of Antxr1 decreased lncRNA H19 expression and Wnt/β-catenin signaling pathway. Hence, our study demonstrates the regulation of Antxr1/LncRNA H19/Wnt/β-catenin axis in the process of mechanical strain-induced osteogenic differentiation, which provides further mechanistic insight into the role of mechanical regulation in bone metabolism.

Influence of Ambient Temperature on Autonomic Nerve Function and Peripheral Sensation from Moderate-Intensity Treadmill Exercise

Influence of Ambient Temperature on Autonomic Nerve Function and Peripheral Sensation from Moderate-Intensity Treadmill Exercise

Comparison the acute effect of moderate-intensity treadmill exercise and arm crank exercise on autonomic cardiac functions in adult male

Background and Study Aim. Cardiovascular parameters testing can be used by various modalities ranging from ground running to sophisticated computerized treadmills. The purpose of this study was to compare the acute effect of treadmill moderate-intensity exercise with arm crank exercise on autonomic cardiac function among adult males. Material and Methods. One hundred-twenty male participants participated in this study. They were randomly allocated to a treadmill exercise group with sixty participants and the other sixty participants allocated into an arm crank exercise group. Both groups performed exercises for forty minutes. Autonomic cardiac functions (heart rate variability - HRV), heartbeats, and arterial blood pressure) were determined with the help of Phillips DigiTrak XT Holter heart rate monitor, Polar® Grit X watch, and automatic sphygmomanometer. An independent t-test was used to compare the anthropometric data between both groups. One-way analysis of variance was used to determine the differences between treadmill exercise and arm crank for autonomic cardiac functions among adult males. Results. The HRV decreased significantly during treadmill exercise than arm crank exercise. Mean values of heartbeats (HR), systolic blood pressure (SBP), and rate pressure product (RPP) increased significantly during both exercises. In comparison, mean values of HRV parameters were reduced more significantly during treadmill exercise than arm crank. Mean values of the HR, SBP, and RPP increased significantly during treadmill exercise than arm crank exercise. Conclusion. The study's findings suggest that treadmill exercises are responsible for a greater significant reduction in HRV. The HR, SBP, PP, and RPP significantly increased during treadmill exercises than arm crank. This study suggests that when recommending exercise to any individual, the intensity and mode of exercise are crucial.

Effects of aerobic exercise on depression-like behavior and TLR4/NLRP3 pathway in hippocampus CA1 region of CUMS-depressed mice

Background and purposeThe paper observes regulation of the expression levels of NLRP3 and TLR4 in hippocampal CA1 neurons in CUMS mice by aerobic exercise with constructing CUMS depression mouse model, in order to explore the neuroprotective mechanism of aerobic exercise on the hippocampus of depressed mice. Study design and method24 healthy male 8-week-old C57BL/6 mice were randomly divided into CG, MG and ME. Thirteen stress-stimulating factors were randomly formulated into a CUMS stress-stimulating program. The mice were underwent 28 days of CUMS depression model, referenced clinical means for experimental research. The study was approved by the Ethics Committee of Yichun University (YCUEC IRB number LSK NO.2022.18). After model preparation, ME mice were subjected to moderate-intensity treadmill exercise training for 8 weeks. TST, FST and SPT were used to detect the depression-like behaviors of the mice in each group. Nissl staining was used to compare the cell morphology in the CA1 region of the mouse hippocampus. Immunohistochemical staining and western blot were used to detect the changes in the expression levels of NLRP3, TLR4 and other proteins in the CA1 region of the mouse hippocampus. ResultsThe results of neurobehavioral assessment showed that, the immobility time of TST and FST were significantly increased, and SPT index was significantly decreased of MG mice. Compared with MG, ME mice significantly improved depression-like behaviors such as TST, FST and SPT index. Nissl staining showed that the morphology of neurons in CA1 region of hippocampus of MG mice were mostly vacuolar-like, with severe nuclear pyknosis. Abnormal morphological changes such as vacuolar-like and pyknotic pyknosis of neurons in the hippocampal CA1 region of ME mice were significantly reduced. Protein expression test showed that the number of NLRP3, TLR4, IL-1β and IL-10 positive neurons in hippocampal CA1 region of MG mice increased significantly compared with CG, and the proportion of positive cells increased significantly, while NLRP3 and TLR4 positive neurons in the hippocampal CA1 region of ME mice were significantly reduced, the proportion of TLR4 positive cells was significantly reduced. ConclusionSystematic moderate-intensity exercise can effectively improve the depression-like behavior of CUMS depressed mice through the expression of TLR4/NLRP3 inflammatory signaling pathway, and provide an effective experimental basis for the clinical rehabilitation treatment of depression.

Alterations in expression of α1-adrenergic receptors possibly are involved in prevention of age-associated apoptosis in rat hippocampus by treadmill exercise.

Exercise is assumed to attenuate age-related neuronal apoptosis, but the detailed mechanism(s) is not fully understood. α1-adrenergic receptors (ARs) can either trigger or suppress apoptosis, therefore, here we determined the impact of treadmill exercise on the expression of the apoptosis regulatory proteins as well as α1-AR subtypes α1A- and α1B-ARs, in order to elucidate a possible association between apoptosis and the hippocampal expression of α1-ARs in aged male rats. Twenty-one male Wistar rats were divided into 3groups (n=7): young control, aged sedentary, and aged+exercise. Western blot for α1A- and α1B-ARs as well as pro-(Bax and p53) and anti-apoptotic (Bcl2) proteins wasconducted. An 8-week regular moderate-intensity treadmill exercise intervention was carried out in exercise group. In aged rats, α1A-AR expression in the hippocampus was significantly increased, and exercise markedly prevented this event. While α1B-AR expression was no altered with aging, a marked reduction in α1B-AR level was detected in exercise group when compared to aged group. Furthermore, pro-apoptotic protein levels of Bax and p53 were upregulated and anti-apoptotic protein Bcl2 was downregulated in the aging hippocampus, but could be reversed by treadmill exercise. In the present research, exercise-induced reduction in α1A- and α1B-ARs was associated with an obvious downregulation of Bax/Bcl2 ratio in aged rats, suggesting that exercise may inhibit apoptosis through regulating α1-ARs, particularly α1A-AR. Our study suggests that manipulations attenuating α1-AR activity, including nonselective α1-adrenergic antagonists, may protect against hippocampal neurodegeneration in aging brains.

Moderate Intensity of Treadmill Exercise Rescues TBI-Induced Ferroptosis, Neurodegeneration, and Cognitive Impairments via Suppressing STING Pathway

Traumatic brain injury (TBI) is a universal leading cause of long-term neurological disability and causes a huge burden to an ever-growing population. Moderate intensity of treadmill exercise has been recognized as an efficient intervention to combat TBI-induced motor and cognitive disorders, yet the underlying mechanism is still unclear. Ferroptosis is known to be highly implicated in TBI pathophysiology, and the anti-ferroptosis effects of treadmill exercise have been reported in other neurological diseases except for TBI. In addition to cytokine induction, recent evidence has demonstrated the involvement of the stimulator of interferon genes (STING) pathway in ferroptosis. Therefore, we examined the possibility that treadmill exercise might inhibit TBI-induced ferroptosis via STING pathway. In this study, we first found that a series of ferroptosis-related characteristics, including abnormal iron homeostasis, decreased glutathione peroxidase 4 (Gpx4), and increased lipid peroxidation, were detected at 44 days post TBI, substantiating the involvement of ferroptosis at the chronic stage following TBI. Furthermore, treadmill exercise potently decreased the aforementioned ferroptosis-related changes, suggesting the anti-ferroptosis role of treadmill exercise following TBI. In addition to alleviating neurodegeneration, treadmill exercise effectively reduced anxiety, enhanced spatial memory recovery, and improved social novelty post TBI. Interestingly, STING knockdown also obtained the similar anti-ferroptosis effects after TBI. More importantly, overexpression of STING largely reversed the ferroptosis inactivation caused by treadmill exercise following TBI. To conclude, moderate-intensity treadmill exercise rescues TBI-induced ferroptosis and cognitive deficits at least in part via STING pathway, broadening our understanding of neuroprotective effects induced by treadmill exercise against TBI.

Evaluation of jacketed telemetry in rats for cardiorespiratory phenotyping at exercise

The challenge of cardiorespiratory function through physical exercise is highly relevant to reveal pathological phenotypes, both in humans and animals, but available monitoring tools (implanted telemetry, metabolic chamber) remain challenging to use in the context of exercise. Recently, jacketed telemetry systems for small laboratory animals have been developed, allowing non-invasive physiological monitoring in various conditions. The aim of this work was to evaluate the feasibility, using this new technology, to monitor cardiorespiratory function during treadmill exercise in rats. The effects of a moderate-intensity treadmill exercise protocol were monitored using a non-invasive telemetric jacket on a group of untrained male wistar rats (N = 9, 9–10 weeks). This incremental protocol consisted in increase the speed level of 5 cm/sec every 2 minutes (Speed: from 10 to 35 cm/sec max). Heart rate (HR), respiratory rate (RespR) and activity level (AL) were monitored with a small electronic Bluetooth device (15 g) and analyzed during a control state (Baseline), the last 30 seconds of each speed level and at post-exercise recovery. The animals were equipped with the device and placed back in their home cage. After 25 minutes of stabilization, HR was 392 ± 36 bpm, RespR was 173 ± 53 brpm, and AL was 15 ± 12 mg. All animals successfully ran on the treadmill with the jacket to the maximum speed of 35 cm/sec. Exercise induced a significant physiological increase in HR (+26%, 104 ± 21 bpm, P < 0.01) and RespR (+73%, 126 ± 22 brpm, P < 0.01). In conclusion, this novel telemetry jacket can be used to monitor cardiorespiratory parameters adaptation during a standard forced exercise protocol. Jacketed telemetry provides a completely non-invasive way to study the phenotypes of animals avoiding any additional risk on fragile pathological models and meeting the regulatory 3Rs requirements. As illustrated phenotype characterization can be enriched with a monitoring of the animal in various situations (treadmill, home cage, but also metabolic or hypoxia cage, etc.…).

Mechanical stress protects against chondrocyte pyroptosis through TGF-β1-mediated activation of Smad2/3 and inhibition of the NF-κB signaling pathway in an osteoarthritis model

Osteoarthritis (OA) is a degenerative disease that is difficult to cure owing to its complicated pathogenesis. Exercise therapy has been endorsed as a primary treatment option. However, it remains controversial how exercise intensity regulates OA progression. Here, a declining propensity for TGF-β1 was predicted via bioinformatics analysis of microarray GSE57218 and validated in cartilage samples obtained from arthroplasty. Based on this, cyclic tensile strain or TGF-β1 intervention was performed on human OA chondrocytes, and we found that moderate-intensity mechanical loads protected chondrocytes against pyroptosis. During this process, the elevation of TGF-β1 is mechanically stimuli-dependent and exerts an inhibitory effect on chondrocyte pyroptosis. Moreover, we elucidated that TGF-β1 activated Smad2/3 and inhibited the NF-κB signaling pathway to suppress chondrocyte pyroptosis. Furthermore, we established a rat knee OA model by intra-articular injection of monosodium iodoacetate and performed treadmill exercises of different intensities. Similar to the in vitro results, we demonstrated that moderate-intensity treadmill exercise had an outstanding chondroprotective effect. An inappropriate intensity of mechanical stimulation may aggravate OA both in vivo and in vitro. Overall, our findings demonstrated that activation of the TGF-β1/Smad2/Smad3 axis and inhibition of NF-κB coordinately inhibit chondrocyte pyroptosis under mechanical loads. This study sheds light on the future development of safe and effective exercise therapies for OA.

Postmenopausal osteoporosis: Effect of moderate-intensity treadmill exercise on bone proteomics in ovariectomized rats.

This study aimed to identify the key proteins in the bone mass of ovariectomized (OVX) rats after a period of regular moderate-intensity treadmill exercise and to investigate their effects using tag mass spectrometry and quantitative proteomics with a view to improving the understanding and treatment of postmenopausal osteoporosis. Sixty three-month-old female Sprague-Dawley tats of specific-pathogen-free grade were randomly and equally divided into a sham operation group, ovariectomized group (OVX) and ovariectomized combined exercise (OVX + EX) group, and the latter took moderate-intensity treadmill exercise for 17 weeks. After this period of time, body composition and bone density were measured using dual-energy x-ray absorptiometry, and serum bone metabolism indicators were measured using an enzyme immunoassay. In addition, the bone microstructure was examined using micro-computed tomography and scanning of the femur, and femur proteins were subject to proteomic analysis. Compared with the rats in the OVX group, the bone metabolism indicators in the OVX + EX group decreased significantly, femur bone density increased significantly, the number of the trabeculae increased, and continuity was higher. In the OVX + EX group, 17 proteins were significantly upregulated and 33 significantly downregulated. The main gene ontology and signaling pathways enriched by the proteins were identified as the tumor necrosis factor-mediated signaling pathways. The protein-protein interaction network identified the key proteins, and the correlation analysis of these proteins and the bone parameters found histone deacetylase 8(HDAC8) and leucine-rich transmembrane and O-methyltransferase domain containing (LRTOMT) and trimethylguanosine synthase 1(TGS1) and ankyrin repeat domain 46(ANKRD46) to be the key targets of exercise in relation to postmenopausal osteoporosis. Moderate-intensity treadmill exercise significantly improved the bone mass of OVX rats, and differentially expressed proteins, such as HDAC8 and LRTOMT and TGS1 and ANKRD46, could be the target of moderate-intensity treadmill exercise.