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Objective: Glucagon-like peptide-1 (GLP1) and leptin (Lep) are afferent signals that regulate energy metabolism. Lactational hypernutrition results in hyperphagia and adiposity in adult life, and these events can be prevented by exercise. We evaluated the effects of swimming training on hypothalamic (GLP1-R) and Lep receptor (Lep-R) gene expressions in lactational hypernutrition-induced obesity., Methods: On the 3rd postnatal day, the litter sizes of lactating dams were adjusted to small litters (SL; 3 pups/dams) or normal litters (NL; 9 pups/dams). After weaning (21 days), NL and SL male rats were randomly distributed to sedentary (Sed) and exercised (Exe) groups. Exercised mice swam (30 min/3 times/week) for 68 days. Food intake and body weight gain were registered. At 92 days, intraperitoneal glucose and insulin tolerance tests were performed and rats were euthanized at 93 days; adipose tissue depots were weighed, and blood counts and plasma biochemical analyses performed. Hypothalamus were isolated to evaluate Lep-R and GLP1-R gene expressions., Results: Small litters sedentary rats presented increased body weight gain, adiposity, insulin sensibility and higher fasting values of glucose and triglycerides, besides higher hypothalamic gene expressions of Lep-R and GLP1-R, compared to NLSed animals. SLExe rats did not develop obesity or metabolic abnormalities and Lep-R and GLP1-R hypothalamic gene expressions were normalized., Conclusion: Lactational hypernutrition induces obesity and metabolic dysfunction in adult life, in association with higher hypothalamic expressions of the Lep-R and GLP1-R genes. Exercise prevented obesity and improved metabolic state in SL overnourished rats, and normalized their hypothalamic Lep-R and GLP1-R gene expressions.

To investigate the role of JAK2/STAT3 signaling pathway in neural function recovery in rats with spinal cord injury (SCI) after treadmill training. Sprague-Dawley rats were randomly divided into four groups: (a) sham group; (b) SCI group; (c) SCI+treadmill training group (SCI/TT); and (d) SCI/TT+AG490 group (a JAK2 inhibitor) ( n  = 12). The 12 Sprague-Dawley rats in each group were randomly assigned into 1 st , 3 rd , 7 th , and 14 th  day subgroups. The Basso-Beattie-Bresnahan (BBB) locomotor rating scale was used to assess the spinal cord function, and JAK2, STAT3, and IL-6 protein expressions in the rat spinal cord were evaluated by western blot. The level of cell apoptosis and expressions of apoptotic proteins were evaluated by TUNEL assay and immunohistochemistry, respectively. Rats in the SCI+TT group showed a significantly higher BBB score after SCI compared with the SCI group and the SCI/TT+AG490 group. Mechanistically, the JAK2/STAT3 signal pathway was immediately activated after SCI compared with sham group, and JAK2 and STAT3 were obviously upregulated when treadmill training was performed ( P  < 0.05). Results of TUNEL assay showed that the apoptotic rate in SCI/TT was significantly lower than that in the SCI group and SCI/TT+AG490 group ( P  < 0.05). Besides, the IL-6 expression in the SCI/TT group was significantly attenuated compared with the SCI group ( P  < 0.05). Our results showed that physical treadmill training can enhance activation of JAK2/STAT3 signal pathway and attenuate apoptosis in the injured spinal cord, resulting in better functional recovery. These results underline the importance of synergistic treatment strategies for SCI., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Alcohol abuse induces various neurological disorders including motor learning deficits, possibly by affecting neuronal and astrocytic activity. Physical exercise is one effective approach to remediate synaptic loss and motor deficits as shown by our previous works. In this study, we unrevealed the role of exercise training in the recovery of cortical neuronal and astrocytic functions. Using a chronic alcohol injection mouse model, we found the hyperreactivity of astrocytes along with dendritic spine loss plus lower neuronal activity in the primary motor cortex. Persistent treadmill exercise training, on the other hand, improved neural spine formation and inhibited reactive astrocytes, alleviating motor learning deficits induced by alcohol exposure. These data collectively support the potency of endurance exercise in the rehabilitation of motor functions under alcohol abuse., (© 2024. The Author(s).)

Exercise training is considered a nonpharmacological therapeutic approach for many diseases. Mild-to-moderate endurance exercise training is suggested to improve the mental and physical state of people with amyotrophic lateral sclerosis (ALS). The aim of the present study was to determine the capacity of symptomatic rNLS8 mice, which develop ALS-reminiscent TAR DNA-binding protein 43 (TDP-43) pathology and motor dysfunction, to perform mild-to-moderate intensity treadmill exercise training and to evaluate the effects of this training on skeletal muscle health and disease progression. Symptomatic rNLS8 mice were able to complete 4 wk of mild-to-moderate treadmill running (30 min at 6-13 m/min, 3 days a week). Exercise training induced an increase in the percentage of type IIA fibers in the tibialis anterior muscle as well as minor adaptations in molecular markers of myogenic, mitochondrial, and neuromuscular junction health in some forelimb and hindlimb muscles. However, this exercise training protocol did not attenuate the loss in motor function or delay disease progression. Alternative exercise regimens need to be investigated to better understand the role exercise training may play in alleviating symptoms of ALS. NEW & NOTEWORTHY This is the first study to investigate the capacity of symptomatic rNLS8 mice, which develop ALS-reminiscent TDP-43 pathology and motor dysfunction, to perform exercise training. We demonstrate that despite the ALS-reminiscent aggressive disease progression characterizing the rNLS8 mouse model, rNLS8 mice are capable of performing mild-to-moderate endurance treadmill training for at least 3-4 wk. We demonstrate that exercise training induces several minor skeletal muscle adaptations without delaying disease progression in rNLS8 mice.

It is unknown whether activity-based physical therapy (ABPT) modalities that mobilize the paralyzed limbs improve bone integrity at the highly fracture-prone epiphyseal regions of the distal femur and proximal tibia following severe spinal cord injury (SCI). In this study, 4-mo-old skeletally mature littermate-matched male Sprague-Dawley rats received either SHAM surgery or severe contusion SCI. At 1 wk postsurgery, SCI rats were stratified to undergo no-ABPT, two 20-min bouts/day of quadrupedal bodyweight-supported treadmill training (qBWSTT), or hindlimb passive isokinetic bicycle (cycle) training, 5 days/wk for another 3 wk. We assessed locomotor recovery and plantar flexor muscle mass, tracked cancellous and cortical bone microstructure at the distal femoral and proximal tibial epiphyses using in vivo microcomputed tomography (microCT), and evaluated bone turnover at the tibial epiphysis with histomorphometry. All SCI animals displayed persistent hindlimb paralysis and pervasive muscle atrophy. Over the initial 2 wk, which included 1 wk of no exercise and 1 wk of ABPT acclimation, a similar magnitude of bone loss developed in all SCI groups. Thereafter, cancellous bone loss and cortical bone decrements increased in the SCI no-ABPT group. qBWSTT attenuated this trabecular bone loss but did not prevent the ongoing cortical bone deficits. In comparison, twice-daily cycle training increased the number and activity of osteoblasts versus other SCI groups and restored all bone microstructural parameters to SHAM levels at both epiphyseal sites. These data indicate that a novel passive isokinetic cycle training regimen reversed cancellous and cortical bone deterioration at key epiphyseal sites after experimental SCI via osteoblast-mediated bone anabolic mechanisms, independent of locomotor recovery or increased muscle mass. NEW & NOTEWORTHY This study was the first to assess how quadrupedal bodyweight-supported treadmill training or passive isokinetic bicycle (cycle) training impacts bone recovery at the distal femoral and proximal tibial epiphyses in a rat model of severe contusion spinal cord injury. Our results demonstrate that passive isokinetic cycle training completely restored cancellous and cortical bone microstructural parameters at these sites via osteoblast-mediated bone anabolic actions, independent of locomotor recovery or increased plantar flexor muscle mass.

Background: Childhood exercise enhances brain structure, while diabetes detrimentally affects it. This study examines early-life exercise's influence on adult diabetic rats' memory and neuroplasticity., Methods: Male Wistar pups were divided into Control, Diabetes, Exercise Training, and Diabetes exercise groups. Diabetes was induced on day 23 with Alloxan (200 mg/kg). A 3-week regimen included aerobic and resistance training thrice weekly. The aerobic intensity was 70%, and resistance varied from 50% to 100% of the maximal carrying capacity (MCC). Following the last training sessions, spatial memory and retrieval tests were performed in infancy, childhood, and emerging adulthood using the Morris Water Maze test (MWM). The hippocampus was excised to measure protein and gene expression of brain-derived neurotrophic factor ( BDNF ), calmodulin-dependent protein kinase ( CAMKII ), N-methyl-D-aspartate receptors ( NMDAR ), and cAMP-response element-binding protein ( CREB ) by western blotting and reverse transcription-polymerase-chain reaction (RT-PCR) methods. Blood samples were collected during each developmental stage to measure glucose levels, at the study's conclusion, to assess Interleukin-1β levels using the ELISA method. The Nissel staining assessed dead hippocampal cells in CA1., Results: Post-natal exercise improved spatial memory ( p  < 0.05) and glucose levels ( p  < 0.05) in diabetic rats during adolescence and emerging adulthood. Despite reduced mRNA expression ( NMDAR 40%, BDNF 62%, CREB 43%, CAMKII 66%), diabetic rats, by study end, showed increased BDNF, NMDARR, CAMKII, CREB protein/gene expression ( p  < 0.05) in emerging adulthood for both training groups., Conclusion: Early-life exercise influenced hippocampal BDNF/NMDAR-CAMKII/CREB pathways in a diabetic rat model, highlighting post-natal exercise's role in neuroplasticity memory enhancement and improved glucose level.

Alleviation of motor impairment by aerobic exercise (AE) in Parkinson's disease (PD) patients points to activation of neurobiological mechanisms that may be targetable by therapeutic approaches. However, evidence for AE-related recovery of striatal dopamine (DA) signaling or tyrosine hydroxylase (TH) loss has been inconsistent in rodent studies. This ambiguity may be related to the timing of AE intervention in relation to the status of nigrostriatal neuron loss. Here, we replicated human PD at diagnosis by establishing motor impairment with >80% striatal DA and TH loss prior to initiating AE, and assessed its potential to alleviate motor decline and restore DA and TH loss. We also evaluated if serum levels of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), biomarkers of human PD severity, changed in response to AE. 6-hydroxydopamine (6-OHDA) was infused unilaterally into rat medial forebrain bundle to induce progressive nigrostriatal neuron loss over 28 days. Moderate intensity AE (3× per week, 40 min/session), began 8-10 days post-lesion following establishment of impaired forelimb use. Striatal tissue DA, TH protein and mRNA, and serum levels of NfL/GFAP were determined 3-wks after AE began. Despite severe striatal DA depletion at AE initiation, forelimb use deficits and hypokinesia onset were alleviated by AE, without recovery of striatal DA or TH protein loss, but reduced NfL and GFAP serum levels. This proof-of-concept study shows AE alleviates motor impairment when initiated with >80% striatal DA loss without obligate recovery of striatal DA or TH protein. Moreover, the AE-related reduction of NfL and GFAP serum levels may serve as objective blood-based biomarkers of AE efficacy., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Vocal and swallowing deficits are common in Parkinson disease (PD). Because these impairments are resistant to dopamine replacement therapies, vocal and lingual exercise are the primary treatment, but not all individuals respond to exercise and neural mechanisms of treatment response are unclear. To explore putative mechanisms, we used the progressive Pink1-/- rat model of early to mid-stage PD and employed vocal and lingual exercises at 6- and 10-months of age in male Pink1-/- and wild type (WT) rats. We hypothesized that vocal and lingual exercise would improve vocal and tongue use dynamics and increase serotonin (5HT) immunoreactivity in related brainstem nuclei. Rats were tested at baseline and after 8 weeks of exercise or sham exercise. At early-stage PD (6 months), vocal exercise resulted in increased call complexity, but did not change intensity, while at mid-stage (10 months), vocal exercise no longer influenced vocalization complexity. Lingual exercise increased tongue force generation and reduced relative optical density of 5HT in the hypoglossal nucleus at both time points. The effects of vocal and lingual exercise at these time points are less robust than in prodromal stages observed in previous work, suggesting that early exercise interventions may yield greater benefit. Future work targeting optimization of exercise at later time points may facilitate clinical translation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Estradiol (E2) deficiency arising from menopause is closely related to changes in body composition and declines of muscle mass and strength in elderly women. Whole-body vibration training (WBV) is an emerging approach expected to improve muscle mass and strength of older person, but the underlying mechanisms remain unclear. The balance between protein synthesis and degradation is a determining factor for muscle mass and strength, which is regulated by Akt-mTOR and FoxO1 signal pathway, respectively. In the present study, we firstly determined whether the effects of WBV on muscle mass and strength in ovariectomized female mice was affected by estrogen level, then investigated whether this was associated with Akt-mTOR and FoxO1 signal pathways. We found that (1) WBV, E2 supplementation (E) and WBV combined with E2 supplementation (WBV+E) significantly increased serum estradiol content, quadriceps muscle mass and grip strength in ovariectomized mice, accompanied with alterations of body composition (reducing fat content, increasing lean body mass and lean percent), furthermore, the altered degrees of these indicators by WBV+E were greater than WBV alone; (2) WBV, E and WBV+E remarkably increased the activities of Akt and mTOR and decreased FoxO1 activity, and the changed degrees by WBV+E were greater than WBV alone; (3) Pearson correlation coefficient revealed that serum estradiol content was positively correlated with Akt and mTOR activities, while inversely associated with FoxO1 activity. We concluded that WBV could significantly increase muscle mass and strength in ovariectomized mice, which might achieve through activating Akt-mTOR and suppressing FoxO1 signal pathways, and the improving effect of WBV on muscle mass and strength was better when in the presence of estrogen., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Status epilepticus is a common and potentially life-threatening neurological emergency with a high risk for cognitive and neurobiological impairment. Our aim was to evaluate the neuroprotective effects of centrally administered irisin and acute exhausting exercise against oxidative brain injury and memory dysfunction due to a pentylenetetrazole (PTZ)-induced single seizure. Male Sprague Dawley rats with intracerebroventricular (icv) cannulas were randomly divided into intraperitoneally (ip) saline-injected control and PTZ-injected (45 mg/kg) seizure groups. Both the control and PTZ groups were then treated with irisin (7.5 µg/kg, 2 µl, icv), saline (2 µl, icv) or were forced to an acute bout of strenuous exercise before the ip injection of saline (control) or PTZ. Seizures were evaluated using the Racine score. To evaluate memory performance, a passive avoidance test was performed before and after PTZ injection. Following euthanasia at the 24th hour of seizure induction, brain tissues were removed for histopathological examination and for evaluating oxidative damage, antioxidant capacity, and neurotransmitter levels., Results: Glutamate/GABA imbalance observed in PTZ rats was corrected by irisin administration (p < 0.001/p < 0.01), while irisin prevented the generation of reactive oxygen species and lipid peroxidation (p < 0.05 - 0.001) and replenished the antioxidant catalase and glutathione levels (p < 0.01-0.01) in the cerebral tissue, and reduced the histologically evident neuronal injury due to a single seizure (p < 0.05 - 0.01). Irisin also delayed the onset of seizures (p < 0.05) and improved memory dysfunction (p < 0.05), but did not affect the severity of seizures. The acute exhaustive swimming exercise completed before PTZ-seizure depressed glutamate level (p < 0.001), maintained the oxidant/antioxidant balance, alleviated neuronal injury (p < 0.05 - 0.01) and upregulated cerebral BDNF expression (p < 0.05)., Conclusion: In conclusion, acute high-intensity exercise or exogenously administered irisin provides neuroprotection by maintaining the balance of excitatory/inhibitory neurotransmitters and oxidant/antioxidant systems., (© 2024. The Author(s).)

Resistance exercise training (RET) is considered an excellent tool for preventing diseases with an inflammatory background. Its neuroprotective, antioxidant, and anti-inflammatory properties are responsible for positively modulating cholinergic and oxidative systems, promoting neurogenesis, and improving memory. However, the mechanisms behind these actions are largely unknown. In order to investigate the pathways related to these effects of exercise, we conducted a 12-week long-term exercise training protocol and used lipopolysaccharide (LPS) to induce damage to the cortex and hippocampus of male Wistar rats. The cholinergic system, oxidative stress, and histochemical parameters were analyzed in the cerebral cortex and hippocampus, and memory tests were also performed. It was observed that LPS: (1) caused memory loss in the novel object recognition (NOR) test; (2) increased the activity of acetylcholinesterase (AChE) and Iba1 protein density; (3) reduced the protein density of brain-derived neurotrophic factor (BDNF) and muscarinic acetylcholine receptor M1 (CHRM1); (4) elevated the levels of lipid peroxidation (TBARS) and reactive species (RS); and (5) caused inflammatory damage to the dentate gyrus. RET, on the other hand, was able to prevent all alterations induced by LPS, as well as increase per se the protein density of the alpha-7 nicotinic acetylcholine receptor (nAChRα7) and Nestin, and the levels of protein thiols (T-SH). Overall, our study elucidates some mechanisms that support resistance physical exercise as a valuable approach against LPS-induced neuroinflammation and memory loss., (© 2024 Wiley Periodicals LLC.)

Postnatal immune activation (PIA) induces persistent glial activation in the brain and causes various neuropathologies in adults. Exercise training improves stress-related mood disorders; however, the role of exercise in psychiatric disorders induced by early-life immune activation and the association between exercise training and glial activation remain unclear. We compared the effects of different exercise intensities on the PIA model, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Both HIIT and MICT in adolescent mice inhibited neuroinflammation, remodeled synaptic plasticity, and improved PIA-induced mood disorders in adulthood. Importantly, HIIT was superior to MICT in terms of reducing inflammation and increasing body weight. RNA-seq of prefrontal cortex (PFC) tissues revealed a gene expression pattern, confirming that HIIT was more effective than MICT in improving brain glial cell activation through epigenetic modifications of KDM6B. We investigated the role of KDM6B, a specific histone lysine demethylation enzyme - histone 3 lysine 27 demethylase, in inhibiting glial activation against PIA-induced depression and anxiety by regulating the expression of IL-4 and brain-derived neurotrophic factor (BDNF). Overall, our data support the idea that HIIT improves PIA-induced mood disorders by regulating KDM6B-mediated epigenetic mechanisms and indicate that HIIT might be superior to MICT in improving mood disorders with PIA in mice. Our findings provide new insights into the treatment of anxiety and depression disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to evaluate the influence of combined intermittent fasting (IF) and high-intensity interval training (HIIT) on morphology, caspase-independent apoptosis signaling pathway, and myostatin expression in soleus and gastrocnemius (white portion) muscles from healthy rats. Sixty-day-old male Wistar rats (n = 60) were divided into four groups: control (C), IF, high-intensity-interval training (T), and high-intensity-interval training and intermittent fasting (T-IF). The C and T groups received ad libitum chow daily; IF and T-IF received the same standard chow every other day. Animals from T and T-IF underwent a HIIT protocol five times a week for 12 weeks. IF reduced gastrocnemius mass and increased pro-apoptotic proteins apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in soleus and cleaved-to-non-cleaved PARP-1 ratio and myostatin expression in gastrocnemius white portion. HIIT increased AIF and apoptosis repressor with caspase recruitment domain expression in soleus and cleaved-to-total PARP-1 ratio in gastrocnemius muscle white portion. The combination of IF and HIIT reduced fiber cross-sectional area in both muscles, increased EndoG and AIF expression, and decreased cleaved-to-non-cleaved PARP-1 ratio in gastrocnemius muscle white portion. Muscle responses to IF and HIIT are directly impacted by the muscle fiber type composition and are modulated, at least in part, by myostatin and caspase-independent apoptosis signaling., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Rational: Patients experience post-stroke cognitive impairment during aging. To date, no specific treatment solution has been reported for this disorder., Objective: The purpose of this study was to evaluate the effects of exercise training and coenzyme Q10 supplementation on middle cerebral artery occlusion (MCAO) induced behavioral impairment, long-term potentiation inhibition and cerebral infarction size in aging rats., Methods: Fifty aging male rats underwent MCAO surgery and were randomly distributed in to the following groups: 1-Sham, 2- control, 3- Coenzyme Q10, 4- Exercise training and 5- Exercise training with Q10 supplementation (Ex + Q10). Aerobic training groups were allowed to run on a treadmill for 12 weeks. Q10 (50 mg/kg) was administered intragastrically by gavage. Morris water maze, shuttle box and elevated plus maze tests were used to evaluate cognitive function. The population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) in the dentate gyrus area were recorded as a result of perforant pathway electrical stimulation., Results: Our study showed that Q10 and aerobic training alone ameliorate spatial memory in the acquisition phase, but have no effect on spatial memory in the retention phase. Q10 and exercise training synergistically promoted spatial memory in the retention phase. Q10 and exercise training separately and simultaneously mitigated cerebral ischemia-induced passive avoidance memory impairment in acquisition and retention phases. The EPSP did not differ between the groups, but exercise training and Q10 ameliorate the PS amplitude in hippocampal responses to perforant path stimulation. Exercising and Q10 simultaneously reduced the cerebral infarction volume., Conclusion: Collectively, the findings of the present study imply that 12 weeks of aerobic training and Q10 supplementation alone can simultaneously reverse cerebral ischemia induced neurobehavioral deficits via amelioration of synaptic plasticity and a reduction in cerebral infarction volume in senescent rats., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Parkinson's disease (PD) is characterized by loss of dopamine neurons in the brain, which leads to motor dysfunction; excessive inflammation induces neuronal death. This study aimed to determine the most effective exercise modality to improve motor dysfunction in PD by comparing three different exercise regimens (low-intensity treadmill, high-intensity treadmill, and swimming)., Materials and Methods: The rat model for PD was established through stereotaxic surgery, inducing unilateral 6-OHDA (6-hydroxydopamine) lesions. The low-intensity treadmill regimen exerted better protective effects on neurological and motor functions in a rat model of unilateral 6-OHDA-induced PD compared to high-intensity treadmill and swimming. The most suitable exercise regimen and the optimal duration of daily exercise (15 or 30 min) on motor activity and oxidative stress parameters were evaluated., Key Findings: Comparison of 15 and 30 min low-intensity treadmill regimens (10 m/min) revealed 30 min daily exercise was the optimal duration and had more favorable impacts on neurological and motor function. Furthermore, we assessed the neuroprotective effects of exercising for 15 and 30 min per day for either four or ten weeks; 30 min of daily exercise for ten weeks improved mitochondrial function, the antioxidant defense system, neurotrophic factors, and muscle mass, and thereby provided protection against dopaminergic neuron loss, and motor dysfunction in rats with 6-OHDA-induced PD., Significance: 30 min of daily low-intensity treadmill exercise over 10 weeks resulted in heightened mitochondrial function in both muscle and brain tissues, therefore, yielded a neuroprotective effect against the loss of dopaminergic neurons and motor dysfunction in PD rats., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024. Published by Elsevier Inc.)

Moderate physical exercise has positive effects on memory. The present study aimed to investigate the impact of long-term exercise on spatial memory in developing mice, as well as its association with the cholinergic system, antioxidant activities, apoptosis factor, and BDNF/PI3K/Akt/CREB pathway in the brain. In this study, Y maze and Novel object recognition (NOR) tests were employed to assess the impact of long-term voluntary exercise on memory. The cholinergic system, antioxidant activities, and apoptosis factors in the brain were quantified using Elisa. Additionally, western blot analysis was conducted to determine the expression of relevant proteins in the BDNF/PI3K/Akt/CREB pathway. The findings demonstrated that prolonged voluntary wheel running exercise enhanced memory in developing mice, concomitant with increased catalase (CAT) activity and decreased malondialdehyde (MDA) levels in the brain. Moreover, it could also increase the hippocampal acetylcholine (ACh) content and suppress the expression of neuronal apoptosis protein. Additionally, exercise also upregulated the expression of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), phosphoinositide 3 kinases (PI3K), Akt, cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB) in the hippocampus. These findings suggest that long-term voluntary wheel running exercise improves the spatial memory of developing mice by modulating the cholinergic system, antioxidant activities, apoptosis factors, and activating the BDNF/PI3K/Akt/CREB pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The abuse of methamphetamine is a significant threat to cardiovascular health and has detrimental effects on the myocardium. The present study aims to explore potential interventions that can mitigate myocardial pyroptosis in rats following methamphetamine withdrawal. A total of 104 male Wistar rats were randomly assigned to eight groups. The rats underwent a methamphetamine administration protocol, receiving intraperitoneal injections of 10 mg/kg during the 1st week, followed by a weekly dose escalation of 1 mg/kg from the second to the 6th week and two times per day. Concurrently, the rats engaged in 6 weeks of moderate-intensity treadmill aerobic training, lasting 60 min per day, 5 days a week. Simultaneously, the Nutrition bio-shield Superfood (NBS) supplement was administered at a dosage of 25 g/kg daily for 6 weeks. The study assessed the expression levels of Caspase-1, Interleukin-1beta (IL-1β), and Interleukin-18 (IL-18) genes in myocardial tissue. Data analysis utilized a one-way analysis of variance (p ≤ 0.05). The findings revealed that methamphetamine usage significantly elevated the expression of Caspase-1, IL-1β, and IL-18 genes (p ≤ 0.05). Conversely, methamphetamine withdrawal led to a notable reduction in the expression of these genes (p ≤ 0.05). Noteworthy reductions in Caspase-1, IL-1β, and IL-18 expression were observed following aerobic training, supplementation, and the combined approach (p ≤ 0.05). The chronic use of methamphetamine was associated with cardiac tissue damage. This study highlights the potential of aerobic training and NBS Superfood supplementation in mitigating the harmful effects of methamphetamine-induced myocardial pyroptosis. The observed reductions in gene expression levels indicate promising interventions to address the cardiovascular consequences of methamphetamine abuse. The findings of this study suggest that a combination of aerobic exercise and NBS Superfood supplementation can provide a promising approach to mitigate the deleterious effects of methamphetamine on the heart. These findings can be useful for healthcare professionals and policymakers to design effective interventions to prevent and manage the adverse effects of methamphetamine abuse., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The myocardium is a highly oxidative tissue in which mitochondria are essential to supply the energy required to maintain pump function. When pathological hypertrophy develops, energy consumption augments and jeopardizes mitochondrial capacity. We explored the cardiac consequences of chronic swimming training, focusing on the mitochondrial network, in spontaneously hypertensive rats (SHR). Male adult SHR were randomized to sedentary or trained (T: 8-week swimming protocol). Blood pressure and echocardiograms were recorded, and hearts were removed at the end of the training period to perform molecular, imaging, or isolated mitochondria studies. Swimming improved cardiac midventricular shortening and decreased the pathological hypertrophic marker atrial natriuretic peptide. Oxidative stress was reduced, and even more interesting, mitochondrial spatial distribution, dynamics, function, and ATP were significantly improved in the myocardium of T rats. In the signaling pathway triggered by training, we detected an increase in the phosphorylation level of both AKT and glycogen synthase kinase-3 β, key downstream targets of insulin-like growth factor 1 signaling that are crucially involved in mitochondria biogenesis and integrity. Aerobic exercise training emerges as an effective approach to improve pathological cardiac hypertrophy and bioenergetics in hypertension-induced cardiac hypertrophy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mitochondria play a crucial role in maintaining cellular energy supply and serve as a source of energy for repairing nerve damage following a stroke. Given that exercise has the potential to enhance energy metabolism, investigating the impact of exercise on mitochondrial function provides a plausible mechanism for stroke treatment. In our study, we established the middle cerebral artery occlusion (MCAO) model in Sprague-Dawley rats and implemented early exercise intervention. Neurological severity scores, beam-walking test score, and weight were used to evaluate neurological function. The volume of cerebral infarction was measured by MRI. Nerve cell apoptosis was detected by TUNEL staining. Mitochondrial morphology and structure were detected by mitochondrial electron microscopy. Mitochondrial function was assessed using membrane potential and ATP measurements. Western blotting was used to detect the protein expression of AMPK/PGC-1α/GLUT4. Through the above experiments, we found that early exercise improved neurological function in rats after MCAO, reduced cerebral infarction volume and neuronal apoptosis, promoted the recovery of mitochondrial morphology and function. We further examined the protein expression of AMPK/PGC-1α/GLUT4 signaling pathway and confirmed that early exercise was able to increase its expression. Therefore, we suggest that early exercise initiated the AMPK/PGC-1α/GLUT4 signaling pathway, restoring mitochondrial function and augmenting energy supply. This, in turn, effectively improved both nerve and body function in rats following ischemic stroke., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To observe the effects of 4 weeks of voluntary wheel running on depressive-like behavior in a rat chronic stress-induced depression model to explore the anti-depressive mechanism of exercise., Methods: In this observational study, 36 Sprague-Dawley rats were randomly divided into control, stress model, and stress exercise groups (12 rats/group). The control group received no intervention, and the stress model and stress exercise group rats underwent chronic mild unpredictable stress and isolation. The stress exercise group rats also underwent 4 weeks of voluntary wheel running. Behavioral changes and hippocampal protein and mRNA expression levels were detected., Results: Voluntary wheel running significantly increased horizontal and vertical movements, sucrose intake, and the sucrose preference percentage and reduced immobility time in the forced swimming test in depression model rats. The hippocampal tumor necrosis factor-α, interleukin (IL)-6, IL-1β, and quinolinic acid levels were significantly decreased, while the IL-4, IL-10, and kynurenic acid levels were significantly increased. Kynurenine-3-monooxygenase and 3-hydroxyanthranilate-3, 4-dioxygenase mRNA levels were downregulated, and kynurenine aminotransferase mRNA was upregulated., Conclusion: Voluntary wheel running improved depressive-like behavior in depression model rats. The mechanism may be related to a kynurenine pathway metabolite level imbalance, which has neurotoxic and neuroprotective effects, caused by long-term voluntary wheel running., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Background: Aortic endothelial diastolic dysfunction is an early complication of diabetes and the abnormal differentiation of Th17 cells is involved in the development of diabetes. However, the exact role of exercise on regulating the Th17 cells differentiation and the underlying molecular mechanisms remain to be elucidated in diabetic mice., Methods: db/db and db/m + mice were randomly divided into exercise and sedentary groups. Mice in exercise group were exercised daily, 6 days/week, for 6 weeks and mice in sedentary groups were placed on a nonmoving treadmill for 6 weeks. Vascular endothelial function was measured via wire myograph and the frequencies of Th17 from peripheral blood in mice were assessed via flow cytometry., Results: Our data showed that exercise improved insulin resistance and aortic endothelial diastolic function in db/db mice. In addition, the proportion of Th17 cells and IL-17A level in peripheral blood of db/db mice were significantly increased, and exercise could promote Th17 cell differentiation and reduce IL-17A level. More importantly, STAT3 or ROR-γt inhibitors could promote Th17 cell differentiation in db/db mice, while exercise significantly down-regulated p-STAT3/ROR-γt signaling in db/db mice, suggesting that exercise regulated Th17 differentiation through STAT3/ROR-γt signaling., Conclusions: This study demonstrated that exercise improved vascular endothelial function in diabetic mice via reducing Th17 cell differentiation through p-STAT3/ROR-γt pathway, suggesting exercise may be an important non-pharmacological intervention strategy for the treatment of diabetes-related vascular complications.

Background: Cerebral Palsy (CP) is a major cause of motor and cognitive disability in children due to injury to the developing brain. Early intensive sensorimotor rehabilitation has been shown to change brain structure and reduce CP symptoms severity. We combined environmental enrichment (EE) and treadmill training (TT) to observe the effects of a one-week program of sensorimotor stimulation (EETT) in animals exposed to a CP model and explored possible mechanisms involved in the functional recovery., Methods: Pregnant Wistar rats were injected with Lipopolysaccharide (LPS - 200 µg/kg) intraperitoneally at embryonic days 18 and 19. At P0, pups of both sexes were exposed to 20' anoxia at 37 °C. From P2 to P21, hindlimbs were restricted for 16 h/day during the dark cycle. EETT lasted from P21 to P27. TT - 15 min/day at 7 cm/s. EE - 7 days in enriched cages with sensorimotor stimulus. Functional 3D kinematic gait analysis and locomotion were analyzed. At P28, brains were collected for ex-vivo MRI and histological assessment. Neurotrophins and key proteins involved in CNS function were assessed by western blotting., Results: CP model caused gross and skilled locomotor disruption and altered CNS neurochemistry. EETT reversed locomotor dysfunction with minor effects over gait kinematics. EETT also decreased brain inflammation and glial activation, preserved myelination, upregulated BDNF signaling and modulated the expression of proteins involved in excitatory synaptic function in the brain and spinal cord., Conclusions: Using this translational approach based on intensive sensorimotor rehabilitation, we highlight pathways engaged in the early developmental processes improving neurological recovery observed in CP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Relapse is a major challenge in the treatment of drug addiction, and exercise has been shown to decrease relapse to drug seeking in animal models. However, the neural circuitry mechanisms by which exercise inhibits morphine relapse remain unclear. In this study, we report that 4-week treadmill training prevented morphine conditioned place preference (CPP) expression during abstinence by acting through the nucleus accumbens (NAc)-ventral pallidum (VP) pathway. We found that neuronal excitability was reduced in D2-dopamine receptor-expressing medium spiny neurons (D2-MSNs) following repeated exposure to morphine and forced abstinence. Enhancing the excitability of NAc D2-MSNs via treadmill training decreased the expression of morphine CPP. We also found that the effects of treadmill training were mediated by decreasing enkephalin levels and that restoring opioid modulation of GABA neurotransmission in the VP, which increased neurotransmitter release from NAc D2-MSNs to VP, decreased morphine CPP. Our findings suggest the inhibitory effect of exercise on morphine CPP is mediated by reversing morphine-induced neuroadaptations in the NAc-to-VP pathway., (© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Aging is accompanied by an increased prevalence of degenerative conditions, including those affecting ocular health, which significantly impact quality of life and increase the burden on healthcare systems. Among these, retinal aging is of particular concern due to its direct link to vision impairment, a leading cause of disability in the elderly. Vision loss in the aging population is associated with heightened risks of cognitive decline, social isolation, and morbidity. This study addresses the critical gap in our understanding of modifiable lifestyle factors, such as physical exercise, that may mitigate retinal aging and its related pathologies. We investigated the effects of different exercise regimens-voluntary (recreational-type) and forced (high-intensity)-on the retinal health of aging Wistar rats (18-month-old), serving as a model for studying the translational potential of exercise interventions in humans. Male Wistar rats were divided into four groups: a young control (3-month-old) for baseline comparison, an aged sedentary control, an aged group engaging in voluntary exercise via a running wheel in their cage, and an aged group subjected to forced exercise on a treadmill for six sessions of 20 min each per week. After a 6-month experimental period, we assessed retinal function via electroretinography (ERG), measured retinal thickness histologically, and analyzed protein expression changes relevant to oxidative stress, inflammation, and anti-aging mechanisms. Our findings reveal that voluntary exercise positively impacts retinal function and morphology, reducing oxidative stress and inflammation markers while enhancing anti-aging protein expression. In contrast, forced exercise showed diminished benefits. These insights underscore the importance of exercise intensity and preference in preserving retinal health during aging. The study highlights the potential of recreational physical activity as a non-invasive strategy to counteract retinal aging, advocating for further research into exercise regimens as preventative therapies for age-related ocular degenerations., (© 2024. The Author(s).)

Exercise increases the expression of brain-derived neurotrophic factor (BDNF) in the brain and contributes to cognitive and sensorimotor functions. This study aimed to elucidate how repeated exercise modifies BDNF expression elicited by a single bout of exercise in the brain using in vivo bioluminescence imaging (BLI). Bdnf-luciferase (Luc) mice with the firefly luciferase gene inserted at the translation start point of the Bdnf gene were used for BLI to monitor changes in BDNF expression in the brain. The treadmill exercise at a speed of 10 m/s for 60 min was repeated 5 days a week for 4 weeks. BLI in individual subjects was repeated four times: before the exercise intervention, on the first exercise day, and 14 and 28 days after the start of the intervention. Each BLI was performed after a single bout of exercise and monitored for 8 h after exercise. Repetitive BLI showed that the exercise regimen enhanced BDNF expression in the brain, specifically at 4-8 h after a single bout of exercise. Repeated exercise for 2 weeks accelerated the start of enhancement after a single bout of exercise, but not after 4 weeks of repeated exercise. This study showed that repeated exercise modulated the time window of exercise-enhanced BDNF expression, suggesting that repeated exercise could change the sensitivity of gene expression to a single bout of exercise. These findings can be attributed to the advantages of in vivo BLI, which allowed us to precisely measure the time course of BDNF expression after repeated exercise in individual subjects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to investigate how intermittent hyperoxic exposure (three cycles of 21% O 2 [10 min] and 30% O 2 [15 min]) affects exercise performance in mice. Three hours after the acute exposure, there was an observed increase in mRNA levels of phosphofructokinase (Bayes factor [BF] ≥ 10), mitochondrial transcription factor-A (BF ≥10), PPAR-α (BF ≥3), and PPAR-γ (BF ≥3) in the red gastrocnemius muscle (Gr). Four weeks of exercise training under intermittent (INT), but not continuous (HYP), hyperoxia significantly (BF ≥30) increased maximal exercise capacity compared to normoxic exercise-trained (ET) group. INT group exhibited significantly higher activity levels of 3-hydroxyacyl-CoA-dehydrogenase (HAD) in Gr (BF = 7.9) compared to ET group. Pyruvate dehydrogenase complex activity levels were significantly higher in INT group compared to ET group in white gastrocnemius, diaphragm, and left ventricle (BF ≥3). NT-PGC1α protein levels in Gr (BF = 7.7) and HAD activity levels in Gr (BF = 6.9) and soleus muscles (BF = 3.3) showed a significant positive correlation with maximal work values. These findings suggest that exercise training under intermittent hyperoxia is a beneficial strategy for enhancing endurance performance by improving fatty acid and pyruvic acid utilization., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Vascular dementia (VD) is the second most common type of dementia worldwide. Previous studies have proven that transcranial direct current stimulation (tDCS) has potential applications in relieving cognitive impairment in VD animal models. The purpose of this study was to probe the mechanism by which tDCS combined with swimming exercise improves the learning and memory abilities of VD model rats., Method: The VD rat model was induced using the permanent bilateral common carotid artery occlusion (2-VO) method; tDCS was applied to the rats and then they took part in swimming exercises. Rat memory, platform crossing time, and platform crossing frequency were analyzed via a water maze experiment. Nerve damage in the cortex and hippocampal CA1 area of the rats was observed using Nissl staining. Western blotting, immunohistochemistry, immunofluorescence staining and reverse transcription quantitative polymerase chain reaction (RT - qPCR) were used to determine the expression of related proteins and genes. The levels of oxidative stress were detected by kits., Results: We demonstrated that VD model rats treated with tDCS combined with swimming exercise exhibited significant improvement in memory, and VD model rats exhibited significantly reduced neuronal loss in the hippocampus, and reduced microglial activation and M1 polarization. tDCS combined with swimming exercise protects VD model rats from oxidative stress through the miR-223-3p/protein arginine methyltransferase 8 (PRMT8) axis and inhibits the activation of the TLR4/NF-κB signaling pathway., Conclusion: Our results suggest that tDCS combined with swimming exercise improved the learning and memory ability of VD model rats by regulating the expression of PRMT8 through miR-223-3p to affect microglial activation and M1 polarization.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and moderate exercise holds promise in ameliorating the ongoing neurodegeneration and cognitive decline. Here, we investigated whether exercise-enriched blood plasm could yield a beneficial therapeutic effect on AD pathologies and cognitive decline in transgenic AD (P301S) mice. In this investigation, a cohort of 2-month-old C57BL/6 mice were granted continuous access to either a running wheel or a fixed wheel for 6 weeks. After that, their plasmas were extracted and subsequently injected intravenously into 4.5-month-old P301S mice biweekly over a 6-week period. A comprehensive methodology was then employed, integrating behavioral tests, pathology assessments, and biochemical analyses to unveil the potential anti-dementia implications of exercise-enriched blood plasma in P301S mice. Upon systemic administration, the findings revealed a noteworthy attenuation of hippocampus-dependent behavioral impairments in P301S mice. Conversely, blood plasma from sedentary counterparts exhibited no discernible impact. These effects were intricately associated with the mitigation of neuroinflammation, the augmentation of hippocampal adult neurogenesis, and a reduction of synaptic impairments following the administration of exercise-enriched blood plasma. These findings advance the proposition that administering exercise-enriched blood plasma may serve as an effective prophylactic measure against AD, opening avenues for further exploration and potential therapeutic interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mitochondrial dysfunction is a significant feature of type 2 diabetes. MOTS-C, a peptide derived from mitochondria, has positive effects on metabolism and exercise capacity. This study explored the impact of high and moderate-intensity interval exercises on mitochondrial MOTS-C alterations and their correlation with metabolic markers in male diabetic sand rats. Thirty male sand rats were divided into six groups: control, MIIT, DM + HIIT, DM + MIIT, DM, and HIIT (5 rats each). Diabetes was induced using a high-fat diet (HFD) combined with streptozotocin (STZ). The Wistar sand rats in exercise groups underwent 8 weeks of interval training of varying intensities. Post sample collection, protein expressions of PCG-1a, AMPK, and GLUT4 were assessed through Western blot analysis, while MOTS-C protein expression was determined using ELISA. Both exercise intensity and diabetes significantly affected the levels of PCG-1a, MOTS-C, GLUT4 proteins, and insulin resistance (p < 0.001). The combined effect of diabetes status and exercise intensity on these levels was also significant (p < 0.001). However, the diabetes effect varied when comparing high-intensity to moderate-intensity exercise. The moderate-intensity exercise group with diabetes showed higher levels of PCG-1a, MOTS-C, and GLUT4 proteins and reduced insulin resistance levels (p < 0.001). Exercise intensity (p = 0.022) and diabetes (p = 0.008) significantly influenced AMPK protein levels. The interplay between diabetes status and exercise intensity on AMPK protein levels was noteworthy, with the moderate-intensity diabetes group exhibiting higher AMPK levels than the high-intensity diabetes group (p < 0.001). In conclusion, exercise elevates the levels of PCG-1a, MOTS-C, GLUT4, and AMPK proteins, regulating insulin resistance in diabetic sand rats. Given the AMPK-MOTS-C mitochondrial pathway's mechanisms, interval exercises might enhance the metabolic rates and general health of diabetic rodents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In the present study, we investigated the effect of high-intensity interval training (HIIT) on cognitive behaviors in female rats with a high-fat diet + streptozotocin (STZ)-induced type 2 diabetes., Methods: Twenty-four female rats were divided into four groups randomly (n = 6): control (C), control + exercise (Co + EX), diabetes mellitus (type 2) (T2D), and diabetes mellitus + exercise (T2D + EX). Diabetes was induced by a two-month high-fat diet and a single dose of STZ (35 mg/kg) in the T2D and T2D + EX groups. The Co + EX and T2D + EX groups performed HIIT for eight weeks (five sessions per week, running on a treadmill at 80-100% of V Max , 4-10 intervals). Elevated plus maze (EPM) and open field test (OFT) were used for assessing anxiety-like behaviors, and passive avoidance test (PAT) and Morris water maze (MWM) were applied for evaluating learning and memory. The hippocampal levels of beta-amyloid (Aβ) and Tau were also assessed using Western blot., Results: An increase in fasting blood glucose (FBG), hippocampal level of Tau, and a decrease in the percentage of open arm time (%OAT) as an index of anxiety-like behavior were seen in the female diabetic rats which could be reversed by HIIT. In addition, T2D led to a significant decrease in rearing and grooming in the OFT. No significant difference among groups was seen for the latency time in the PAT and learning and memory in the MWM., Conclusions: HIIT could improve anxiety-like behavior at least in part through changes in hippocampal levels of Tau., (© 2024. The Author(s).)

Voluntary or forced exercise training in mice is used to assess functional capacity as well as potential disease-modifying effects of exercise over a range of cardiovascular disease phenotypes. Compared to voluntary wheel running, forced exercise training enables precise control of exercise workload and volume, and results in superior changes in cardiovascular performance. However, the use of a shock grid with treadmill-based training is associated with stress and risk of injury, and declining compliance with longer periods of training time for many mouse strains. With these limitations in mind, we designed a novel, high-intensity interval training modality (HIIT) for mice that is carried out on a rotarod. Abbreviated as RotaHIIT, this protocol establishes interval workload intensities that are not time or resource intensive, maintains excellent training compliance over time, and results in improved exercise capacity independent of sex when measured by treadmill graded exercise testing (GXT) and rotarod specific acceleration and endurance testing. This protocol may therefore be useful and easily implemented for a broad range of research investigations. As RotaHIIT training was not associated cardiac structural or functional changes, or changes in oxidative capacity in cardiac or skeletal muscle tissue, further studies will be needed to define the physiological adaptations and molecular transducers that are driving the training effect of this exercise modality., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Hypertensive postmenopausal women are more likely to develop adverse cardiac remodeling and respond less effectively to drug treatment than men. High-intensity interval exercise (HIIE) is a nonpharmacological strategy for the treatment of hypertension; however, the effectiveness in women remains uncertain. This study was designed to evaluate 1 ) the effects of HIIE training upon morphological and functional markers of cardiovascular health in female SHR and 2 ) to determine whether the hormonal shift induced by ovariectomy could influence cardiovascular responses to HIIE. Thirty-six SHR were randomly assigned to four groups: ovariectomized sedentary, ovariectomized trained, sham-operated sedentary, and sham-operated trained. The trained rats performed HIIE 5 days/wk for 8 wk. Blood pressure and echocardiographic measurements were performed before and after training in animals. Cardiac response to β-adrenergic stimulation and the expression of calcium regulatory proteins and estrogen receptors in heart samples were assessed. Endothelium-dependent vasorelaxation in response to acetylcholine was evaluated in aortic rings as well as the expression of nitric oxide synthase isoforms (eNOS and P-eNOS) by Western blotting. In both groups of trained SHR, HIIE induced eccentric cardiac remodeling with greater inotropic and chronotropic effects, as well as an increase in SERCA and β1AR expression. However, although the trained rats showed improved endothelial function and expression of eNOS and P-eNOS in the aorta, there was no demonstrated effect on blood pressure. In addition, the responses to HIIE training were not affected by ovariectomy. This work highlights the importance of assessing the cardiovascular efficacy and safety of different exercise modalities in women. NEW & NOTEWORTHY This study reports the effects of high-intensity interval exercise (HIIE) training on cardiac and endothelial function in female hypertensive rats. Despite a lack of effect on blood pressure (BP), HIIE training induces eccentric cardiac remodeling with greater functionals effects. Furthermore, training has beneficial effects on endothelial function. However, ovarian hormones do not seem to modulate cardiac and aortic adaptations to this training modality. All this underlines the need to consider training modalities on the cardiovascular system in women.

This study aimed to determine whether heat acclimation could induce adaptations in exercise performance, thermoregulation, and the expression of proteins associated with heat stress in the skeletal muscles of Thoroughbreds. Thirteen trained Thoroughbreds performed 3 weeks of training protocols, consisting of cantering at 90% maximal oxygen consumption (VO 2max ) for 2 min 2 days/week and cantering at 7 m/s for 3 min 1 day/week, followed by a 20-min walk in either a control group (CON; Wet Bulb Globe Temperature [WBGT] 12-13°C; n = 6) or a heat acclimation group (HA; WBGT 29-30°C; n = 7). Before and after heat acclimation, standardized exercise tests (SET) were conducted, cantering at 7 m/s for 90 s and at 115% VO 2max until fatigue in hot conditions. Increases in run time (p = 0.0301), peak cardiac output (p = 0.0248), and peak stroke volume (p = 0.0113) were greater in HA than in CON. Pulmonary artery temperature at 7 m/s was lower in HA than in CON (p = 0.0332). The expression of heat shock protein 70 (p = 0.0201) and 90 (p = 0.0167) increased in HA, but not in CON. These results suggest that heat acclimation elicits improvements in exercise performance and thermoregulation under hot conditions, with a protective adaptation to heat stress in equine skeletal muscles., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Significant bowel-related issues after spinal cord injury (SCI) that affect morbidity and quality of life (QOL) include diminished bowel motility, loss of sphincter control, gastric ulcers, autonomic dysreflexia, pain, diarrhea, constipation, and fecal incontinence. Clinical diagnoses and research in humans have largely relied on anorectal manometry (ARM) procedures to increase understanding of the functional effects of SCI on colorectal motility and defecation physiology. Recent pre-clinical rodent studies have also used ARM to further our understanding of bowel-related dysfunctions post-SCI. In the present study, the benefits of different activity-based training (ABT) durations on bowel function were examined. Six groups of male rats including two non-training (NT; uninjured and SCI) and four ABT (quadrupedal [Quad or Q] stepping on a treadmill) groups. All ABT animals received 4 weeks of 1-h daily stepping beginning 2 weeks post-SCI followed by variable amounts for 4 additional weeks (none; daily; once a week; daily for final 4th week only). Outcome measures included fecal output (home cage; metabolic cage) throughout the study and terminal measurements (post 8-week ABT) of external anal sphincter (EAS) electromyography, resting anorectal pressure, and giant contraction (GC) activation under urethane anesthesia. The results indicate that treadmill training normalized defecation amount based on feces weight and food intake, as well as GC frequency, EAS latency and amplitude during fecal expulsion, and resting pressure in specific areas within the colorectum. The two intermittent training groups consistently showed recorded metrics comparable to the non-injured group. The results demonstrate bowel dysfunction in the rodent SCI contusion model with improvements in functional outcomes following ABT. Importantly, the benefits to bowel-related functions with versus without intermittent ABT illustrate the need for periodic therapy to maintain the functional gains of ABT.

A common anthracycline antibiotic used to treat cancer patients is doxorubicin (DOX). One of the effects of DOX therapy is skeletal muscle fatigue. Our goal in this research was to study the beneficial effect of exercise on DOX-induced damaged muscle fibers and compare the effect of different exercise strategies (prophylactic, post- toxicity and combined) on DOX toxicity. Five groups were created from 40 male rats: group I, control group; group II, DOX was administered intraperitoneally for 2 weeks over 6 equal injections (each 2.5 mg/kg); group III, rats trained for 3 weeks before DOX; group IV, rats trained for 8 weeks after DOX; and group V, rats were trained for 3 weeks before DOX followed by 8 weeks after. Measures of oxidative damage (H 2 O 2 , catalase), inflammation (TNF-α), and glucose transporter 4 (GLUT4) expression on skeletal muscle were assessed. Also, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was estimated. Skeletal performance was evaluated by contraction time (CT), half relaxation time (1/2 RT), and force-frequency relationship by the end of this research. The current study demonstrated a detrimental effect of DOX on skeletal performance as evidenced by a significant increase in CT and 1/2 RT compared to control; in addition, H 2 O 2 , TNF-α, and HOMA-IR were significantly increased with a significant decrease in GLUT4 expression and catalase activity. Combined exercise therapy showed a remarkable improvement in skeletal muscle performance, compared to DOX, CT, and 1/2 RT which were significantly decreased; H 2 O 2 and TNF-α were significantly decreased unlike catalase antioxidant activity that significantly increased; in addition, skeletal muscle glucose metabolism was significantly improved as GLUT4 expression significantly increased and HOMA-IR was significantly decreased. Exercise therapy showed significant improvement in all measured parameters relative to DOX. However, combined exercise therapy showed the best improvement relative to both pre-exercise and post-exercise groups., (© 2024. The Author(s).)

The developmental origins of health and disease concept highlights the impact of early environments on chronic non-communicable diseases like diabetes, cardiovascular disease, and cancer. Studies using animal models have investigated how maternal factors such as undernutrition, overnutrition, obesity, and exposure to chemicals or hypoxia affect fetal development and offspring health, leading to issues like low birth weight, high blood pressure, dyslipidemia, and insulin resistance. Given the increasing prevalence of overweight and obesity among reproductive-age women, effective interventions are critical. Maternal exercise during pregnancy has emerged as a key intervention, benefiting both mother and offspring and reducing the risk of disease. This study compares the differences of three exercise models on pregnant rats: voluntary wheel running, motorized treadmills, and swimming. Swimming is the most beneficial option due to its safe and controlled intensity levels. This protocol details the rat breeding methods, swimming training during pregnancy, and post-breeding nursing protocols. This model, suitable for various rat and mouse species, is useful for studying the benefits of maternal exercise on offspring health and intergenerational wellness.

The effects of exercise training (ET) on the heart of aortic stenosis (AS) rats are controversial and the mechanisms involved in alterations induced by ET have been poorly clarified. In this study, we analyzed the myocardial proteome to identify proteins modulated by moderate-intensity aerobic ET in rats with chronic supravalvular AS. Wistar rats were divided into four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary aortic stenosis (AS-Sed), and exercised AS (AS-Ex). ET consisted of five treadmill running sessions per week for 16 weeks. Statistical analysis was performed by ANOVA or Kruskal-Wallis and Goodman tests. Results were discussed at a significance level of 5%. At the end of the experiment, AS-Ex rats had higher functional capacity, lower blood lactate concentration, and better cardiac structural and left ventricular (LV) functional parameters than the AS-Sed. Myocardial proteome analysis showed that AS-Sed had higher relative protein abundance related to the glycolytic pathway, oxidative stress, and inflammation, and lower relative protein abundance related to beta-oxidation than C-Sed. AS-Ex had higher abundance of one protein related to mitochondrial biogenesis and lower relative protein abundance associated with oxidative stress and inflammation than AS-Sed. Proteomic data were validated for proteins related to lipid and glycolytic metabolism. Chronic pressure overload changes the abundance of myocardial proteins that are mainly involved in lipid and glycolytic energy metabolism in rats. Moderate-intensity aerobic training attenuates changes in proteins related to oxidative stress and inflammation and increases the COX4I1 protein, related to mitochondrial biogenesis. Protein changes are combined with improved functional capacity, cardiac remodeling, and LV function in AS rats., (© 2024 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.)

Objective: To identify subclinical left ventricle dysfunction (LVD) in obese rats by speckle-tracking echocardiography, and to evaluate the effects of 12-week Moderate-Intensity Continuous Training (MICT) or High-Intensity Interval Training (HIIT) on LV geometry, histology and function in obese rats., Methods: Eighteen male standard or obese Sprague-Dawley rats were randomly divided into the Control group, the MICT group, and the HIIT group. Exercise interventions were conducted for 12 weeks, with equal total load and increased intensity gradient. Using dual-energy X-ray, two-dimensional speckle-tracking echocardiography, pulse Doppler, and HE staining to evalucate body shape, LV morphology, structure, and myocardial mechanics function., Results: (1) Both MICT and HIIT have good weight loss shaping effect. (2) The LV of obese rats underwent pathological remodeling, with decreased longitudinal contractility and synchrony, and increased circumferential contractility and synchrony. (3) Exercise can inhibit LV pathological remodeling, improve myocardial mechanical function. HIIT is superior to MICT. (4) The global longitudinal strain of obese rats in the HIIT group showed a significant correlation with Fat% and Lean%., Conclusion: Obesity can induce LV pathological remodeling and subclinical dysfunction. Compared with MICT, 12-week HIIT can effectively inhibit the pathological remodeling of LV and promote the benign development of myocardial mechanical function in obese rats., Competing Interests: Declaration of Competing Interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Introduction: This study aimed to investigate the potential of short-term aerobic exercise to mitigate skeletal muscle mitochondrial damage following ambient PM2.5 exposure, and how 12 weeks of endurance training can enhance aerobic fitness to protect against such damage., Methods: Twenty-four male C57BL/6 J mice were split into sedentary (SED, n  = 12) and endurance training (ETR, n  = 12) groups. The ETR group underwent 12 weeks of training (10-15 m/min, 60 min/day, 4 times/week), confirmed by an Endurance Exercise Capacity (EEC) test. Post-initial training, the SED group was further divided into SSED (SED and sedentary, n  = 6) and SPE (SED and PM2.5 + Exercise, n  = 6). Similarly, the ETR group was divided into EEX (ETR and Exercise, n  = 6) and EPE (ETR and PM2.5 + Exercise, n  = 6). These groups underwent 1 week of atmospherically relevant artificial PM2.5 exposure and treadmill running (3 times/week). Following treatments, an EEC test was conducted, and mice were sacrificed for blood and skeletal muscle extraction. Blood samples were analyzed for oxidative stress indicators, while skeletal muscles were assessed for mitochondrial oxidative metabolism, antioxidant capacity, and mitochondrial damage using western blot and transmission electron microscopy (TEM)., Results: After 12 weeks of endurance training, the EEC significantly increased ( p < 0.000) in the ETR group compared to the SED group. Following a one-week comparison among the four groups with atmospherically relevant artificial PM2.5 exposure and exercise treatment post-endurance training, the EEX group showed improvements in EEC, oxidative metabolism, mitochondrial dynamics, and antioxidant functions. Conversely, these factors decreased in the EPE group compared to the EEX. Additionally, within the SPE group, exercise effects were evident in HK2, LDH, SOD2, and GPX4, while no impact of short-term exercise was observed in all other factors. TEM images revealed no evidence of mitochondrial damage in both the SED and EEX groups, while the majority of mitochondria were damaged in the SPE group. The EPE group also exhibited damaged mitochondria, although significantly less than the SPE group., Conclusion: Atmospherically relevant artificial PM2.5 exposure can elevate oxidative stress, potentially disrupting the benefits of short-term endurance exercise and leading to mitochondrial damage. Nonetheless, increased aerobic fitness through endurance training can mitigate PM2.5-induced mitochondrial damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Wang, Gu, So, Kook, Park and Kim.)

Background: Oxidative stress plays a major role in the progression of Alzheimer's disease (AD)-related cognitive deficits., Objective: This study was done to determine the protective effects of coenzyme Q10 (CoQ10) and high-intensity interval training (HIIT) alone and in combination for eight continuous weeks, on oxidative status, cognitive functions, and histological changes in the hippocampus in amyloid-β (Aβ)-induced AD rats., Methods: Ninety male Wistar rats were randomly assigned to the sham, control, Q10 (50 mg/kg of CoQ10; P.O.), HIIT (high intensity: 4 min running at 85-90% VO2max, low intensity: 3 min running at 50-60% VO2max), Q10 + HIIT, AD, AD+Q10, AD+HIIT, and AD+Q10 + HIIT groups., Results: The results showed that Aβ injection reduced cognitive functions in the Morris water maze (MWM) test and recognition memory in the novel object recognition test (NORT), which was accompanied by a decrease in total thiol groups, catalase, and glutathione peroxidase activities, an increase in malondialdehyde levels, and neuronal loss in the hippocampus. Interestingly, pretreatment with CoQ10, HIIT, or both, could markedly improve the oxidative status and cognitive decline in the MWM and NOR tests, and hinder neuronal loss in the hippocampus of Aβ-induced AD rats., Conclusion: Therefore, a combination of CoQ10 and HIIT can improve Aβ-related cognitive deficits, probably through an amelioration in hippocampal oxidative status and prevention of neuronal loss.

Skeletal muscle contractile function is impaired in menopause and exercise may mitigate this decline. We used the 4-vinylcyclohexene diepoxide (VCD) model of menopause to investigate the effects of gradual ovarian failure on skeletal muscle contractile function and whether high-intensity interval training (HIIT) can mitigate impairments. Sexually mature female CD-1 mice were assigned to one of three groups: control sedentary ( n = 5), VCD-sedentary ( n = 5), or VCD-training ( n = 5). Following ovarian failure (a 4-mo process), the VCD-training group underwent 8 wk of uphill HIIT. Mice were euthanized 8 wk after ovarian failure, representing late menopause. Single fibers from the soleus (SOL) and extensor digitorum longus (EDL) muscles were dissected, chemically permeabilized, and mechanically tested. Single muscle fibers were maximally activated (pCa 4.5), then isotonic load clamps were performed to evaluate force-velocity-power relationships. Absolute force and peak power were 31.0% and 32.2% lower in VCD-sedentary fibers compared with control fibers, respectively, in both SOL and EDL muscles. Despite reductions in absolute force, there were no concomitant increases in contractile velocity to preserve power production. HIIT attenuated force loss in the VCD-training group such that peak force was not different from the control group across muscles and was partially effective at mitigating power loss (21.7% higher peak power in VCD-training compared with VCD-sedentary) but only in fast-type SOL fibers. These findings indicate that ovarian failure impairs dynamic contractile function-likely through a combination of lower force-generating capacity and slower shortening velocity-and that HIIT may be insufficient to completely counteract the deleterious effects of menopause at the cellular level. NEW & NOTEWORTHY We used the VCD model of menopause to investigate the effects of gradual ovarian failure on skeletal muscle contractile function and whether high-intensity interval training (HIIT) can mitigate impairments. Our findings indicate that ovarian failure impairs dynamic contractile function-likely through a combination of lower force-generating capacity and slower shortening velocity-and that HIIT may be insufficient to completely counteract the deleterious effects of menopause at the cellular level.

Compared to continuous-moderate or low-intensity training, high-intensity interval training (HIIT) is a more time-efficient alternative method that results in similar physiologic benefits. This paper presents a HIIT protocol that can be used to assess various health markers in a Sprague-Dawley rat model of diet-induced obesity. Female Sprague Dawley rats aged 21 days old were randomly assigned to the following groups: control (CON, n = 10), exercise-trained (TRN, n = 10), high-fat diet (HFD, n = 10), and high-fat diet/exercise training (HFD/TRN, n = 10). The control diets consisted of commercial laboratory chow with 10% kilocalories (kcal) from fat (3.82 kcal/g), and the high-fat diets (HFD) consisted of 45% kcal from fat (4.7 kcal/g). The animals had ad libitum access to their assigned diet throughout the study. After an 8 week diet induction period, the exercise cohorts completed four HIIT sessions per week for 8 weeks. Each HIIT session consisted of 10 intervals of 1 min sprints/2 min rest using a rodent treadmill with a motor-driven belt. After the 8 weeks of training, the animals were sacrificed for tissue collection. The results revealed no differences in the distance run between the TRN and HFD/TRN groups, and the training speed steadily increased over the duration of the study, with a final running speed of 115 cm/s and 111 cm/s for the TRN and HFD/TRN groups, respectively. The weekly caloric intake was decreased (p < 0.05) in the TRN group relative to the CON group but increased (p < 0.05) in the HFD/TRN group relative to the HFD group. Lastly, the animals on the HFD had greater (p < 0.05) adiposity, and the trained animals had reduced (p < 0.05) adiposity relative to controls. This protocol demonstrates an efficient method to evaluate the effects of HIIT on various physiologic outcomes in a diet-induced obesity model.

Good aerobic fitness associates positively with cognitive performance and brain health and conversely, low aerobic fitness predisposes to neurodegenerative diseases. To study how genotype together with exercise, started at older age, affects brain and behavior, we utilized rats that differ in inherited aerobic fitness. Rats bred for Low Capacity for Running (LCR) are shown to display less synaptic plasticity and more inflammation in the hippocampus and perform worse than rats bred for a High Capacity for Running (HCR) in tasks requiring flexible cognition. Here we used middle-aged (∼ 16 months) HCR and LCR rats to study how genotype and sex associate with anxiety and neural information filtering, termed sensory gating. Further, we assessed how inherited aerobic capacity associates with hippocampus-dependent learning, measured with contextual fear conditioning task. In females, we also investigated the effects of voluntary wheel running (5 weeks) on these characteristics. Our results indicate that independent of sex or voluntary running, HCR rats were more anxious in open-field tasks, exhibited lower sensory gating and learned more efficiently in contextual fear conditioning task than LCR rats. Voluntary running did not markedly affect innate behavior but slightly decreased the differences between female LCR and HCR rats in fear learning. In conclusion, inherited fitness seems to determine cognitive and behavioral traits independent of sex. Although the traits proved to be rather resistant to change at adult age, learning was slightly improved following exercise in LCR females, prone to obesity and poor fitness., Competing Interests: Competing interests None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Exercise training can increase both mitochondrial content and mitochondrial respiration. Despite its popularity, high-intensity exercise can be accompanied by mild acidosis (also present in certain pathological states), which may limit exercise-induced adaptations to skeletal muscle mitochondria. The aim of this study was to determine if administration of ammonium chloride (0.05 g/kg) to Wistar rats before each individual exercise session (5 high-intensity exercise sessions/wk for 8 wk) reduced training-induced increases in mitochondrial content (measured by citrate synthase activity and protein content of electron transport system complexes) and respiration (measured in permeabilized muscle fibers). In the soleus muscle, the exercise-training-induced increase in mitochondrial respiration was reduced in rats administered ammonium chloride compared to control animals, but mitochondrial content was not altered. These effects were not present in the white gastrocnemius muscle. In conclusion, ammonium chloride administration before each exercise session over 8 wk reduced improvements in mitochondrial respiration in the soleus muscle but did not alter mitochondrial content. This suggests that mild acidosis may affect training-induced improvements in the respiration of mitochondria in some muscles.

We investigated the effects of aging and long-term physical activity on markers of mitochondrial function and dynamics in the cortex and cerebellum of female rats. Additionally, we interrogated markers of oxidative damage and antioxidants. Thirty-four female Lewis rats were separated into three groups. A young group (YNG, n = 10) was euthanized at 6 months of age. Two other groups were aged to 15 months and included a physical activity group (MA-PA, n = 12) and a sedentary group (MA-SED, n = 12). There were no age effects for any of the variables investigated, except for SOD2 protein levels in the cortex (+6.5%, p = 0.012). Long-term physical activity increased mitochondrial complex IV activity in the cortex compared to YNG (+85%, p = 0.016) and MA-SED (+82%, p = 0.023) and decreased carbonyl levels in the cortex compared to YNG (-12.49%, p = 0.034). Our results suggest that the mitochondrial network and redox state of the brain of females may be more resilient to the aging process than initially thought. Further, voluntary wheel running had minimal beneficial effects on brain markers of oxidative damage and mitochondrial physiology., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objective: To investigate the effects of continuing exercise and load-bearing interval exercise on skeletal muscle tissue cell morphology, Ras-related proteins 5 (Rab5) mRNA and protein expression and glucose metabolism in skeletal muscle of type 2 diabetic mellitus (T2DM) rats. Methods: Eight SD rats were selected as controls group (CR), the others SD rats were fed with high fat and high sugar diet for 6 weeks before injecting STZ (35 mg/kg) to construct the T2DM model. Twenty-four T2DM rats were randomly devided into T2DM model group (DRM), continuing exercise group (DCRE) and load-bearing interval exercise group (DWRE), 8 rats in each group. DCRE exercise protocol, that was 15 m/min (10 min), 20 m/min (40 min), 15 m/min (10 min), during the first 1～2 weeks, and 18 m/min (10 min), 25 m/min (40 min), 15 m/min (10 min), during the second 3～8 weeks. DWRE exercise protocol: load weight 15% / 1～2 weeks, 30% / 3～4 weeks, 45% / 5～8 weeks, with 15 m/min (5 min), 12 groups and 3 min rest between groups. After 8 weeks, pathological and morphological changes of skeletal muscle were observed by HE. Rab5 and Glucose transporte 4 (GLUT4) mRNA expressions of skeletal muscle were tested by qRT-PCR. Rab5 protein expression in skeletal muscle was tested by immunofluorescence histochemistry and Western blot, and plasma Rab5 and Glycosylated Hemoglobin (GHb) concentrations were detected by ELISA. Results: Comparison with CR, DRM showed pathological damage of skeletal muscle, the expressions of Rab5 mRNA, protein and GLUT4 mRNA were all decreased in skeletal muscle ( P ＜0.01), the serum levels of Rab5 and GHb were both significantly elevated ( P ＜0.01). Comparison with DRM, both DCRE and DWRE significantly improved pathological damages of skeletal muscle, the expressions of Rab5 mRNA, protein and GLUT4 mRNA were all increased in skeletal muscle ( P ＜ 0.05, P ＜0.01), the serum levels of Rab5 and GHb were decreased ( P ＜0.05, P ＜0.01), and there was no statistical difference between DCRE and DWRE groups ( P ＞0.05). Conclusion: Two exercise modes can improve the pathological injury of skeletal muscle in type 2 diabetic rats, and enhance GLUT4 transport capacity by improving the expression of Rab5 gene and protein in skeletal muscle, and alleviate the imbalance of glucose metabolism homeostasis in skeletal muscle. However, there was no significant difference between the effects of two exercise modes on Rab5 protein and glucose metabolism in skeletal muscle.

The temporal pattern of cortical plasticity induced by high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) is required to clarify their relative benefits to prevent neurological disorders. The purpose of this study is to define the time-dependent effects of work-matched HIIT and MICT on cortical plasticity, endurance, and sensorimotor performances over an 8-week training period in healthy rats. Adult healthy rats performed incremental exercise tests and sensorimotor tests before and at 2, 4, and 8 weeks of training. In parallel, cortical markers related to neurotrophic, angiogenic, and metabolic activities were assessed. Results indicate that HIIT induced an early and superior endurance improvement compared to MICT. We found significant enhancement of speed associated with lactate threshold (SLT) and maximal speed (Smax) in HIIT animals. MICT promoted an early increase in brain-derived neurotrophic factor and angiogenic/metabolic markers but showed less influence at 8 weeks. HIIT upregulated the insulin-like growth factor-1 (IGF-1) as well as neurotrophic, metabolic/angiogenic markers at 2 and 8 weeks and downregulated the neuronal K-Cl cotransporter KCC2 that regulates GABAA-mediated transmission. HIIT and MICT are effective in a time-dependent manner suggesting a complementary effect that might be useful in physical exercise guidelines for maintaining brain health., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Water treadmill (WT) exercise is frequently used for training/rehabilitation of horses. There is limited study into the effect of water depth on limb/back kinematics warranting investigation. The objective was to determine the effect of walking in different water depths, at the same speed, on limb/back kinematics measured simultaneously in a group of horses. Six horses (age:15 ± 6.5 years) completed a standardized WT exercise session (19 minutes duration; speed:1.6 m/s; water depths: 0.0/7.5/21.0/32.0/47.0 cm). Ten waterproof light-emitting-diode tea-light-markers and reflective-spheres were affixed to the skin at predetermined locations; inertial-measurement-units were fixed to the poll/withers/left and right tubera coxae (TC)/sacrum to determine range-of-motion (ROM) changes of these locations. Univariable-mixed-effects-linear-regression-analyses were carried out, with a significance value of P ≤ .05. At maximum carpal/tarsal flexion during swing, regression analyses showed a clear and consistent nonlinear increase in carpal and tarsal flexion at increasing water depths (P < 0.0001 for both variables). As water depth increased there was a significant increase in thoracic spine flexion-extension ROM (P < 0.0001 at all thoracic sites) and increased dorsoventral and mediolateral ROM of the sacrum/left and right TC (P < 0.001 for all variables) as water depth increased. Results suggest that horses responded to an increase in water depth until a threshold depth was reached when the biomechanical response levelled off, and there was increased pelvic roll. In conclusion, changes in limb kinematics brought about by relatively modest increases in water depth at walking speed of 1.6 m/s are sufficient to induce significant changes in back/pelvic movement highlighting key issues with relevance for WT program design., (Copyright © 2022. Published by Elsevier Inc.)

Hypertension is associated with blood-brain barrier alteration and brain function decline. Previously, we established the 2-kidney,1-clip (2K1C) hypertensive mice model by renin-angiotensin system (RAS) stimulating. We found that 2K1C-induced hypertension would impair hippocampus-related memory function and decrease adult hippocampal neurogenesis. Even though large studies have investigated the mechanism of hypertension affecting brain function, there remains a lack of efficient ways to halt this vicious effect. The previous study indicated that running exercise ameliorates neurogenesis and spatial memory function in aging mice. Moreover, studies showed that exercise could normalize RAS activity, which might be associated with neurogenesis impairment. Thus, we hypothesize that running exercise could ameliorate neurogenesis and spatial memory function impairment in the 2K1C-hypertension mice. In this study, we performed 2K1C surgery on eight-weeks-old C57BL/6 mice and put them on treadmill exercise one month after the surgery. The results indicate that running exercise improves the spatial memory and neurogenesis impairment of the 2K1C-mice. Moreover, running exercise normalized the activated RAS and blood-brain barrier leakage of the hippocampus, although the blood pressure was not decreased. In conclusion, running exercise could halt hypertension-induced brain impairment through RAS normalization.

Previously developed rodent resistance-based exercise models, including synergistic ablation, electrical stimulation, weighted-ladder climbing, and most recently, weighted-sled pulling, are highly effective at providing a hypertrophic stimulus to induce skeletal muscle adaptations. While these models have proven invaluable for skeletal muscle research, they are either invasive or involuntary and labor-intensive. Fortunately, many rodent strains voluntarily run long distances when given access to a running wheel. Loaded wheel running (LWR) models in rodents are capable of inducing adaptations commonly observed with resistance training in humans, such as increased muscle mass and fiber hypertrophy, as well as stimulation of muscle protein synthesis. However, the addition of moderate wheel load either fails to deter mice from running great distances, which is more reflective of an endurance/resistance training model, or the mice discontinue running nearly entirely due to the method of load application. Therefore, a novel high-load wheel running model (HLWR) has been developed for mice where external resistance is applied and progressively increased, enabling mice to continue running with much higher loads than previously utilized. Preliminary results from this novel HLWR model suggest it provides sufficient stimulus to induce hypertrophic adaptations over the 9 week training protocol. Herein, the specific procedures to execute this simple yet inexpensive progressive resistance-based exercise training model in mice are described.