Voluntary Exercise Research Articles

Nucleus accumbens D1- and D2-expressing neurons control the balance between feeding and activity-mediated energy expenditure

Accumulating evidence points to dysregulations of the Nucleus Accumbens (NAc) in eating disorders (ED), however its precise contribution to ED symptomatic dimensions remains unclear. Using chemogenetic manipulations in male mice, we found that activity of dopamine D1 receptor-expressing neurons of the NAc core subregion facilitated effort for a food reward as well as voluntary exercise, but decreased food intake, while D2-expressing neurons have opposite effects. These effects are congruent with D2-neurons being more active than D1-neurons during feeding while it is the opposite during running. Chronic manipulations of each subpopulations had limited effects on energy balance. However, repeated activation of D1-neurons combined with inhibition of D2-neurons biased behavior toward activity-related energy expenditure, whilst the opposite manipulations favored energy intake. Strikingly, concomitant activation of D1-neurons and inhibition of D2-neurons precipitated weight loss in anorexia models. These results suggest that dysregulations of NAc dopaminoceptive neurons might be at the core of EDs.

Abstract P478: Short-Term Voluntary Exercise Significantly Influences the Diet-Induced Changes in Cecal Microbial Content in Male Mice

Two leading environmental factors that influence the overall health of humans are diet and physical exercise. However, it is still unclear how these factors influence health and disease susceptibility. Both diet and exercise have been shown to modulate the microbial flora that may significantly influence health and disease; however, it is unclear if diet modulates the effects of exercise on gut microflora. Therefore, this study aimed to determine how diet and exercise modulate the microbial content of the mouse cecum. Male, weanling, C57Bl/6 mice were randomly assigned to receive one of three diets ad libitum: standard laboratory chow, AIN93-G, and our novel Americanized diet (AD). Within each diet, mice were then assigned to a voluntary exercise regimen (wheel access, 16-hours per day, 3-days per week) or a control sedentary group (individually housed in cage without wheel for the same duration and frequency). After 2-weeks of exercise, mice were euthanized and cecal microbial content was determined by16S rDNA sequencing and RT-PCR for Firmicutes (FIRM), Bifidobacterium (GBIFD), Lactobacillus (LB) , and Bacteroides (BACT). Data were analyzed using GLM Procedures in SPSS with significance determined at P<0.05. Pilot results found that diet, exercise, and their interaction significantly influenced FIRM expression. Mice fed the standard chow diet had the lowest expression of FIRM , which was significantly lower than mice fed AIN (P<0.001) and AD (P=0.001). Exercise caused a significant decrease (P<0.001) in FIRM presence, especially in mice fed AIN and AD. Diet and exercise also significantly influenced GBIFD , with mice fed AIN having significantly more GBIFD than mice fed chow and AD (P<0.001 for both). Exercise also caused a significant reduction (P=0.016) in GBIFD , and a reduction in LB expression in mice fed chow and AD, but not AIN (P=0.03). The results of this study highlight how two key aspects of lifestyle, diet and exercise, independently and additively influence the gastrointestinal flora in a preclinical mouse model. Additional studies are needed to validate these findings and determine their physiological significance.

Differential changes in blood flow and oxygen utilization in active muscles between voluntary exercise and electrical muscle stimulation in young adults.

The physiological effects on blood flow and oxygen utilization in active muscles during and after involuntary contraction triggered by electrical muscle stimulation (EMS) remain unclear, particularly compared with those elicited by voluntary (VOL) contractions. Therefore, we used diffuse correlation and near-infrared spectroscopy (DCS-NIRS) to compare changes in local muscle blood flow and oxygen consumption during and after these two types of muscle contractions in humans. Overall, 24 healthy young adults participated in the study, and data were successfully obtained from 17 of them. Intermittent (2-s contraction, 2-s relaxation) isometric ankle dorsiflexion with a target tension of 20% of maximal VOL contraction was performed by EMS or VOL for 2 min, followed by a 6-min recovery period. DCS-NIRS probes were placed on the tibialis anterior muscle, and relative changes in local tissue blood flow index (rBFI), oxygen extraction fraction (rOEF), and metabolic rate of oxygen (rMRO2) were continuously derived. EMS induced more significant increases in rOEF and rMRO2 than VOL exercise but a comparable increase in rBFI. After EMS, rBFI and rMRO2 decreased more slowly than after VOL and remained significantly higher until the end of the recovery period. We concluded that EMS augments oxygen consumption in contracting muscles by enhancing oxygen extraction while increasing oxygen delivery at a rate similar to the VOL exercise. Under the conditions examined in this study, EMS demonstrated a more pronounced and/or prolonged enhancement in local muscle perfusion and aerobic metabolism compared with VOL exercise in healthy participants.NEW & NOTEWORTHY This is the first study to visualize continuous changes in blood flow and oxygen utilization within contracted muscles during and after electrical muscle stimulation (EMS) using combined diffuse correlation and near-infrared spectroscopy. We found that initiating EMS increases blood flow at a rate comparable to that during voluntary (VOL) exercise but enhances oxygen extraction, resulting in higher oxygen consumption. Furthermore, EMS increased postexercise muscle perfusion and oxygen consumption compared with that after VOL exercise.

The effect of neuromuscular electrical stimulation on the human skeletal muscle transcriptome.

The influence on acute skeletal muscle transcriptomics of neuromuscular electrical stimulation (NMES), as compared to established exercises, is poorly understood. We aimed to investigate the effects on global mRNA-expression in the quadriceps muscle early after a single NMES-session, compared to the effects of voluntary knee extension exercise (EX), and to explore the discomfort level. Global vastus lateralis muscle gene expression was assessed (RNA-sequencing) in 30 healthy participants, before and 3 h after a 30-min session of NMES and/or EX. The NMES-treatment was applied using textile electrodes integrated in pants and set to 20% of each participant's pre-tested MVC mean (±SD) 200 (±80) Nm. Discomfort was assessed using Visual Analogue Scale (VAS, 0-10). The EX-protocol was performed at 80% of 1-repetition-maximum. NMES at 20% of MVC resulted in VAS below 4 and induced 4448 differentially expressed genes (DEGs) with 80%-overlap of the 2571 DEGs of EX. Genes well-known to be up-regulated following exercise, for example, PPARGC1A, ABRA, VEGFA, and GDNF, were also up-regulated by NMES. Gene set enrichment analysis demonstrated many common pathways after EX and NMES. Also, some pathways were exclusive to either EX, for example, muscle tissue proliferation, or to NMES, for example, neurite outgrowth and connective tissue proliferation. A 30-min NMES-session at 20% of MVC with NMES-pants, which can be applied with an acceptable level of discomfort, induces over 4000 DEGs, of which 80%-overlap with DEGs of EX. NMES can induce exercise-like molecular effects, that potentially can lead to health and performance benefits in individuals who are unable to perform resistance exercise.

Social jet lag impairs exercise volume and attenuates physiological and metabolic adaptations to voluntary exercise training.

Social jet lag (SJL) is a misalignment between sleep and wake times on workdays and free days. SJL leads to chronic circadian rhythm disruption and may affect nearly 70% of the general population, leading to increased risk for cardiometabolic diseases. This study investigated the effects of SJL on metabolic health, exercise performance, and exercise-induced skeletal muscle adaptations in mice. Ten-week-old C57BL/6J mice (n = 40) were allocated to four groups: control sedentary (CON-SED), control exercise (CON-EX), social jet lag sedentary (SJL-SED), and social jet lag exercise (SJL-EX). CON mice were housed under a 12:12-h light-dark cycle. SJL was simulated by implementing a 4-h phase delay for 3 days to simulate "weekends," followed by a 4-h phase advance back to "weekdays," for 6 wk. EX mice had free access to a running wheel. Graded exercise tests (GXTs) and glucose tolerance tests (GTTs) were performed at baseline and after intervention to monitor the effects of exercise and social jet lag on cardiorespiratory and metabolic health, respectively. SJL led to alterations in activity and running patterns and clock gene expression in skeletal muscle and decreased average running distance (P < 0.05). SJL-SED mice gained significantly more weight compared with CON-SED and SJL-EX mice (P < 0.01). SJL impaired fasting blood glucose and glucose tolerance compared with CON mice (P < 0.05), which was partially restored by exercise in SJL-EX mice. SJL also blunted improvements in exercise performance and mitochondrial content in the quadriceps. These data suggest that SJL blunted some cardiometabolic adaptations to exercise and that proper circadian hygiene is necessary for maintaining health and performance.NEW & NOTEWORTHY In mice, disrupting circadian rhythms with social jet lag for 6 wk caused significant weight gain, higher fasting blood glucose, and impaired glucose tolerance compared with control. Voluntary exercise in mice experiencing social jet lag prevented weight gain, though the mice still experienced increased fasting blood glucose and impaired exercise performance compared with trained mice not experiencing social jet lag. Social jet lag seems to be a potent circadian rhythm disruptor that impacts exercise-induced training adaptations.

Endurance exercise preserves physical function in adult and older male C57BL/6 mice: high intensity interval training (HIIT) versus voluntary wheel running (VWR).

Exercise has been shown to improve physical function, mitigate aspects of chronic disease and to potentially alter the trajectory of age-related onset of frailty and sarcopenia. Reliable and valid preclinical models are necessary to elucidate the underlying mechanisms at the intersection of age, exercise, and functional decline. The purpose of this study was to compare, head to head, the effects of two common pre-clinical models of endurance exercise: high intensity interval training (HIIT) and voluntary wheel running (VWR). The hypothesis was that a prescribed and regimented exercise program, HIIT, would prove to be a superior training method to unregulated voluntary exercise, VWR. To investigate this hypothesis, we evaluated adult (n = 24, designated 10m, aged 6 months at the beginning of the study, 10 months at its completion) and older adult (n = 18, designated 26m, aging from 22 months to 26 months over the course of the study) C57BL/6 male mice. These mice were randomly assigned (with selection criteria) to a 13-week program of voluntary wheel running (VWR), high intensity interval training (HIIT), or sedentary control (SED). The functional aptitude of each mouse was determined pre- and post-training using our composite CFAB (comprehensive functional assessment battery) scoring system consisting of voluntary wheel running (volitional exercise and activity rate), treadmill (endurance), rotarod (overall motor function), grip meter (forelimb strength), and inverted cling (whole body strength/endurance). To measure sarcopenia, we tracked body mass, body composition (with EchoMRI), plantar flexor torque (in 10m), and measured muscle wet mass post-training. Overall, adult CFAB scores decreased while body mass and percent body fat increased as they matured; however, exercise significantly mitigated the changes (p < 0.05) compared to SED. Older adults demonstrated preservation of function (CFAB) and reduced body fat (p < 0.05) compared to SED. To conclude, both types of exercise maintained physical function equally in older mice.

Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise.

JOURNAL/nrgr/04.03/01300535-202503000-00028/figure1/v/2024-06-17T092413Z/r/image-tiff Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group (10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Exercise attenuates the perioperative neurocognitive disorder induced by hyperhomocysteinemia in mice

The perioperative neurocognitive disorder (PND) is a severe complication that affects millions of surgical patients each year. Homocysteine (Hcy) is known to increase the risk of developing PND in both young and elderly mice. However, whether Hcy alone can induce cognitive deficits in middle-aged mice (12-month-old), whether exercise can attenuate Hcy-induced hippocampus-related cognitive deficits after surgery through suppressing neuroinflammation, synaptic elimination, and the level of Hcy remains unknown. The present study aimed to answer these questions through testing the possibility of establishing a PND model using 12-month-old mice which received homocysteine injections before exploratory laparotomy and the therapeutic mechanism of exercise. In the present study, it was found that levels of serum homocysteine were age-dependently increased in mice with a significant difference between that of 18-month-old mice and 6-week, 6-month, and 12-month-old mice. PND occurred in 18-month but not in 12-month-old mice after exploratory laparotomy under isoflurane anesthesia. Intraperitoneal injection of Hcy for 3 consecutive days before surgery rendered 12-month-old mice to develop PND after abdominal laparotomy under isoflurane anesthesia at a minimal dosage of 20mg/kg. Neuroinflammation and synaptic elimination was present in 12-month-old preoperative Hcy-injected mice. Preoperative voluntary wheel exercise could prevent PND in 12-month-old mice that have received Hcy injection before surgery, which might be related to the decreased level of serum Hcy. Activation of glial cells, proinflammatory phenotype markers and synaptic elimination were attenuated in the hippocampus of 12-month-old preoperative Hcy-injected mice by this exercise. These results provide direct evidence that hyperhomocysteinemia can induce postoperative cognitive deficits in middle-aged mice. Pre-surgery exercise can effectively prevent Hcy-precipitated postoperative cognitive dysfunction.

Exercise and insulin glargine administration in mothers with diabetes during pregnancy ameliorate function of testis in offspring: Consequences on apelin-13 and its receptor

AimsDespite the evidence exhibited that diabetes during gestation (DDG) is linked with reproductive dysfunction in offspring, the underlying cellular mechanisms involved are not precisely defined. This study was designed to assess the impact of voluntary exercise and insulin glargine on DDG-induced metabolic and reproductive disorders in male offspring. Main methodsFifty female Wistar rats (three weeks old) received a control diet (n = 10) or high-fat-high-sucrose diet (to induce DDG; n = 40) for six weeks before breeding. From the 7th day of pregnancy onwards, blood glucose over 140 mg/dL was characterized as DDG. Then, the DDG animals were randomly divided into four subgroups with/without voluntary exercise and/or insulin glargine. To evaluate insulin resistance, a glucose tolerance test was performed on the 15th day of pregnancy. After three weeks, male offspring were weaned, and fed a control diet until 12 weeks old. At the end of the experiment, the lipid profile, sex hormones, and apelin-13 in the serum, mRNA expression of apelin receptors (APJ) in the testis and sperm analysis were assessed. Key findingsOur results indicated that voluntary exercise and/or insulin glargine administration in mothers with DDG ameliorated lipid profile, and sex hormones alterations, reduced the serum level of apelin-13, as well as increased APJ expression in testis, and quality of sperm in offspring. SignificanceCombined administration of voluntary exercise and insulin glargine during pregnancy by regulating of apelinergic system and inhibiting the metabolic and reproductive complications induced by DDG, can be considered as a suitable therapeutic strategy for improving sub-or in-fertility in the male offspring.

Orexinergic neurons contribute to autonomic cardiovascular regulation for locomotor exercise.

While the hypothalamic orexinergic nervous system is established as having a pivotal role in the long-term regulation of various organismic functions, including wakefulness, metabolism and hypertensive states, whether this system contributes to the rapid autonomic cardiovascular regulation during physical activity remains elusive. This study aimed to elucidate the role of the orexinergic nervous system in transmitting volitional motor signals, i.e. central command, to drive somatomotor and sympathetic cardiovascular responses. We first found that this system is activated by voluntary locomotor exercise as evidenced by an increased expression of Fos, a marker of neural activation, in the orexinergic neurons of Sprague-Dawley rats engaged in spontaneous wheel running. Next, using transgenic Orexin-Cre rats for optogenetic manipulation of orexinergic neurons, we found that optogenetic excitation of orexinergic neurons caused sympathoexcitation on a subsecond timescale under anaesthesia. In freely moving conscious rats, this excitatory stimulation rapidly elicited exploration-like behaviours, predominantly locomotor activity, along with pressor and tachycardiac responses. Meanwhile, optogenetic inhibition of orexinergic neurons during spontaneous wheel running immediately suppressed locomotor activities and blood pressure elevation without affecting basal cardiovascular homeostasis. Taken together, these findings demonstrate the essential role of the orexinergic nervous system in the central circuitry that transmits central command signals for locomotor exercise. This study not only offers insights into the brain circuit mechanisms precisely regulating autonomic cardiovascular systems during voluntary exercise but also likely contributes to our understanding of brain mechanisms underlying abnormal cardiovascular adjustments to exercise in pathological conditions, such as hypertension. KEY POINTS: The hypothalamic orexinergic nervous system plays various roles in the long-term regulation of autonomic and endocrine functions, as well as motivated behaviours. We present a novel, rapid role of the orexinergic nervous system, revealing its significance as a crucial substrate in the brain circuit mechanisms that coordinate somatomotor and autonomic cardiovascular controls for locomotor exercise. Our data demonstrate that orexinergic neurons relay volitional motor signals, playing a necessary and sufficient role in the autonomic cardiovascular regulation required for locomotor exercise in rats. The findings contribute to our understanding of how the brain precisely regulates autonomic cardiovascular systems during voluntary exercise, providing insights into the central neural mechanisms that enhance physical performance moment-by-moment during exercise.

Cardiac reverse remodeling in a mouse model with many phenotypical features of heart failure with preserved ejection fraction: effects of modifying lifestyle.

Multiple factors cause heart failure with preserved ejection fraction (HFpEF) and involve various systems. HFpEF prevalence is rapidly rising, and its prognosis remains poor after the first hospitalization. Adopting a more active lifestyle has been shown to provide beneficial clinical outcomes for patients with HFpEF. Using a two-hit HfpEF murine model, we studied cardiac reverse remodeling (RR) after stopping the causing stress and introducing voluntary exercise (VE). We checked in 2-mo-old male and female C57Bl6/J mice the heart's response to angiotensin II (ANG II; 1.5 mg/kg/day for 28 days) fed or not with a high-fat diet (HFD). Then, ANG II and/or the HFD were stopped, and VE was started for an additional 4 wk. ANG II and ANG II + HFD (metabolic-hypertensive stress, MHS) caused cardiac hypertrophy (CH) and myocardial fibrosis, left ventricular (LV) concentric remodeling, atrial enlargement, and reduced exercise capacity. HFD alone induced CH and LV concentric remodeling in female mice only. CH and LV concentric remodeling were reversed 4 wk after stopping ANG II, starting VE, and a low-fat diet. Left atrial enlargement and exercise capacity were improved but differed from controls. We performed bulk LV RNA sequencing and observed that MHS upregulated 58% of the differentially expressed genes (DEGs) compared with controls. In the RR group, compared with MHS animals, 60% of the DEGs were downregulated. In an HfpEF mouse model, we show that correcting hypertension, diet, and introducing exercise can lead to extensive cardiac reverse remodeling.NEW & NOTEWORTHY Using a two-hit murine model of heart failure with preserved ejection fraction (HfpEF), combining elevated blood pressure, obesity, and exercise intolerance in male and female animals, we showed that correction of hypertension, normalization of the diet, and introduction of voluntary exercise could help reverse the remodeling of the left ventricle and double exercise capacity. We also identify genes that escape normalization after myocardial recovery and differences between males' and females' responses to stress and recovery.

Exercise mitigates flow recirculation and activates metabolic transducer SCD1 to catalyze vascular protective metabolites.

Exercise promotes pulsatile shear stress in the arterial circulation and ameliorates cardiometabolic diseases. However, exercise-mediated metabolic transducers for vascular protection remain under-investigated. Untargeted metabolomic analysis demonstrated that wild-type mice undergoing voluntary wheel running exercise expressed increased endothelial stearoyl-CoA desaturase 1 (SCD1) that catalyzes anti-inflammatory lipid metabolites, namely, oleic (OA) and palmitoleic acids (PA), to mitigate NF-κB-mediated inflammatory responses. In silico analysis revealed that exercise augmented time-averaged wall shear stress but mitigated flow recirculation and oscillatory shear index in the lesser curvature of the mouse aortic arch. Following exercise, endothelial Scd1-deleted mice (Ldlr-/- Scd1EC-/-) on high-fat diet developed persistent VCAM1-positive endothelium in the lesser curvature and the descending aorta, whereas SCD1 overexpression via adenovirus transfection mitigated endoplasmic reticulum stress and inflammatory biomarkers. Single-cell transcriptomics of the aorta identified Scd1-positive and Vcam1-negative endothelial subclusters interacting with other candidate genes. Thus, exercise mitigates flow recirculation and activates endothelial SCD1 to catalyze OA and PA for vascular endothelial protection.

Effects of long-term voluntary wheel running and selective breeding for wheel running on femoral nutrient canals.

The nutrient artery provides ~50%-70% of the total blood volume to long bones in mammals. Studying the functional characteristics of this artery invivo can be difficult and expensive, so most researchers have measured the nutrient foramen, an opening on the outer surface of the bone that served as the entry point for the nutrient artery during development and bone ossification. Others have measured the nutrient canal (i.e., the passage which the nutrient artery once occupied), given that the external dimensions of the foramen do not necessarily remain uniform from the periosteal surface to the medullary cavity. The nutrient canal, as an indicator of blood flow to long bones, has been proposed to provide a link to studying organismal activity (e.g., locomotor behavior) from skeletal morphology. However, although external loading from movement and activity causes skeletal remodeling, it is unclear whether it affects the size or configuration of nutrient canals. To investigate whether nutrient canals can exhibit phenotypic plasticity in response to physical activity, we studied a mouse model in which four replicate high runner (HR) lines have been selectively bred for high voluntary wheel-running behavior. The selection criterion is the average number of wheel revolutions on days 5 and 6 of a 6-day period of wheel access as young adults (~6-8 weeks old). An additional four lines are bred without selection to serve as controls (C). For this study, 100 female mice (half HR, half C) from generation 57 were split into an active group housed with wheels and a sedentary group housed without wheels for 12 weeks starting at ~24 days of age. Femurs were collected, soft tissues were removed, and femora were micro-computed tomography scanned at a resolution of 12 μm. We then imported these scans into AMIRA and created 3D models of femoral nutrient canals. We tested for evolved differences in various nutrient canal traits between HR and C mice, plastic changes resulting from chronic exercise, and the selection history-by-exercise interaction. We found few differences between the nutrient canals of HR versus C mice, or between the active and sedentary groups. We did find an interaction between selection history and voluntary exercise for the total number of nutrient canals per femur, in which wheel access increased the number of canals in C mice but decreased it in HR mice. Our results do not match those from an earlier study, conducted at generation 11, which was prior to the HR lines reaching selection limits for wheel running. The previous study found that mice from the HR lines had significantly larger total canal cross-sectional areas compared to those from C lines. However, this discrepancy is consistent with studies of other skeletal traits, which have found differences between HR and C mice to be somewhat inconsistent across generations, including the loss of some apparent adaptations with continued selective breeding after reaching a selection limit for wheel-running behavior.

Relationship between paravertebral muscle function, pelvic incidence, and health-related quality of life in patients with degenerative spinal deformity

BackgroundPatients with degenerative spinal deformity often experience symptoms that seriously affect their quality of life, such as low back pain and dysfunction. This study aimed to investigate the relationship between paravertebral muscle function and pelvic incidence (PI) and their effect on health-related quality of life (HRQL) in patients with degenerative spinal deformity.MethodsA total of 112 patients with degenerative spinal deformity in Southwest Hospital (Chongqing, China) were enrolled. They were divided into groups according to PI angle: high (PI > 60°, n = 37), normal (PI 50°–60°, n = 31), and low (PI < 50°, n = 44). Paravertebral muscle strength and endurance were assessed using the prone external fixation test frame. The sagittal vertical axis (SVA) was measured on X-rays of the spine in an anterolateral position, and all subjects were assessed with the Oswestry Disability Index (ODI), Roland–Morris questionnaire (RMQ), and 36-Item Short Form Health Survey (SF-36). Pearson or Spearman coefficients were used to assess the relationship of paravertebral muscle function with SVA, PI, and health-related quality of life.ResultsMaximal voluntary exercise (MVE) in the high-PI group was significantly lower than the MVE of both the normal- and low-PI groups (p < 0.05). There was no significant difference in MVE between the normal- and low-PI groups (p > 0.05). There was no significant difference in endurance time, SVA, ODI, RMQ, and SF-36 among the three groups. Paravertebral muscle MVE was negatively correlated with PI, SVA, ODI, and RMQ (r = − 0.193, − 0.210, − 0.283, − 0.277, p < 0.05). Endurance time of paravertebral muscle was also negatively correlated with SVA, ODI, and RMQ (r = − 0.200, − 0.420, − 0.348, p < 0.05) and positively correlated with SF-36 (r = 0.245, p < 0.05). In addition, paravertebral muscle MVE was positively correlated with the physical functioning score of the SF-36 (r = 0.251, p < 0.05), and the endurance time of paravertebral muscle was positively correlated with the physical functioning, physical role, bodily pain, and social function scores of the SF-36 (r = 0.342, 0.230, 0.209, 0.256, p < 0.05).ConclusionsHigh PI may serve as a risk factor for decreased paraspinal muscle strength in patients with degenerative spinal deformities. Early and targeted exercises focusing on paraspinal muscle strength and endurance could potentially be of positive significance in slowing down the progression of sagittal imbalance, alleviating functional disorders, and increasing health-related quality of life in patients with degenerative spinal deformity.

The plasma metabolome is associated with preservation of physiological function following lifelong aerobic exercise in mice.

Declines in physiological function with aging are strongly linked to age-related diseases. Lifelong voluntary aerobic exercise (LVAE) preserves physiological function with aging, possibly by increasing cellular quality control processes, but the circulating molecular transducers mediating these processes are incompletely understood. The plasma metabolome may predict biological aging and is impacted by a single bout of aerobic exercise. Here, we conducted an ancillary analysis using plasma samples, and physiological function data, from previously reported studies of LVAE in male C57BL/6N mice randomized to LVAE (wheel running) or sedentary (SED) (n = 8-9/group) to determine if LVAE alters the plasma metabolome and whether these changes correlated with preservation of physiological function with LVAE. Physical function (grip strength, coordination, and endurance) was assessed at 3 and 18months of age; vascular endothelial function and the plasma metabolome were assessed at 19months. Physical function was preserved (%decline; mean ± SEM) with LVAE vs SED (all p < 0.05)-grip strength, 0.4 ± 1.7% vs 12 ± 4.0%; coordination, 10 ± 4% vs 73 ± 10%; endurance, 1 ± 15% vs 61 ± 5%. Vascular endothelial function with LVAE (88.2 ± 2.0%) was higher than SED (79.1 ± 2.5%; p = 0.03) and similar to the young controls (91.4 ± 2.9%). Fifteen metabolites were different with LVAE compared to SED (FDR < 0.05) and correlated with the preservation of physiological function. Plasma spermidine, a polyamine that increases cellular quality control (e.g., autophagy), correlated with all assessed physiological indices. Autophagy (LC3A/B abundance) was higher in LVAE skeletal muscle compared to SED (p < 0.01) and inversely correlated with plasma spermidine (r = - 0.5297; p = 0.054). These findings provide novel insight into the circulating molecular transducers by which LVAE may preserve physiological function with aging.

A Single-Cell Transcriptomic Analysis of the Mouse Hippocampus After Voluntary Exercise

Exercise has been recognized as a beneficial factor for cognitive health, particularly in relation to the hippocampus, a vital brain region responsible for learning and memory. Previous research has demonstrated that exercise-mediated improvement of learning and memory in humans and rodents correlates with increased adult neurogenesis and processes related to enhanced synaptic plasticity. Nevertheless, the underlying molecular mechanisms are not fully understood. With the aim to further elucidate these mechanisms, we provide a comprehensive dataset of the mouse hippocampal transcriptome at the single-cell level after 4 weeks of voluntary wheel-running. Our analysis provides a number of interesting observations. For example, the results suggest that exercise affects adult neurogenesis by accelerating the maturation of a subpopulation of Prdm16-expressing neurons. Moreover, we uncover the existence of an intricate crosstalk among multiple vital signaling pathways such as NF-κB, Wnt/β-catenin, Notch, and retinoic acid (RA) pathways altered upon exercise in a specific cluster of excitatory neurons within the Cornu Ammonis (CA) region of the hippocampus. In conclusion, our study provides an important resource dataset and sheds further light on the molecular changes induced by exercise in the hippocampus. These findings have implications for developing targeted interventions aimed at optimizing cognitive health and preventing age-related cognitive decline.

Age-Dependent Effects of Voluntary Wheel Running Exercise on Voiding Behavior and Potential Age-Related Molecular Mechanisms in Mice.

Older men frequently develop lower urinary tract symptoms attributed to benign prostatic hyperplasia (LUTS/BPH). Risk factors for LUTS/BPH include sedentary lifestyle, anxiety/depression, obesity, and frailty, which all increase with age. Although physical exercise may reduce the progression and/or severity of LUTS/BPH, the age-related mechanisms responsible remain unknown. Voiding symptoms, body mass, and frailty were assessed after 4-weeks of voluntary wheel running in 2-month (n = 10) and 24-month (n = 8) old C57Bl/6J male mice. In addition, various social and individual behaviors were examined in these cohorts. Finally, cellular and molecular markers of inflammation and mitochondrial protein expression were assessed in prostate tissue and systemically. Despite running less (aged vs young X¯ = 12.3 vs 30.6 km/week; p = .04), aged mice had reduced voiding symptoms (X¯ = 67.3 vs 23.7; p < .0001) after 1 week of exercise, which was sustained through week 4 (X¯ = 67.3 vs 21.5; p < .0001). Exercise did not affect voiding symptoms in young mice. Exercise also increased mobility and decreased anxiety in both young and aged mice (p < .05). Exercise decreased expression of a key mitochondrial protein (PINK1; p < .05) and inflammation within the prostate (CD68; p < .05 and plasminogen activator inhibitor-1; p < .05) and in the serum (p < .05). However, a frailty index (X¯ = 0.17 vs 0.15; p = .46) and grip strength (X¯ = 1.10 vs 1.19; p = .24) were unchanged after 4 weeks of exercise in aged mice. Voluntary aerobic exercise improves voiding behavior and mobility, and decreases prostatic mitochondrial protein expression and inflammation in aged mice. This promising model could be used to evaluate molecular mechanisms of aerobic exercise as a novel lifestyle intervention for older men with LUTS/BPH.

Obesity-Resistant Mice on a High-Fat Diet Display a Distinct Phenotype Linked to Enhanced Lipid Metabolism.

Individually, metabolic variations can significantly influence predisposition to obesity in the form of the obesity-prone (super-responders) and obesity-resistant (non-responders) phenotypes in response to modern calorie-dense diets. In this study, C57BL/6J mice (n = 76) were randomly assigned to either a low-fat diet (LFD) or a high-fat diet (HFD) for 6 weeks, followed by selection of the normally obese (HFD), non-responders (NR), super-responders (SR), or super-responders switched back to the low-fat diet (SR-LFD) for an additional 8 weeks. SR mice showed the highest gains in body weight, lean and fat body mass, and total and free water, in part due to increased feed efficiency, despite having a respiratory exchange ratio (RER) similar to that of NR mice. A switch to the LFD was sufficient to revert most of the observed physiological changes in the SR-LFD mice; however, voluntary physical activity and exercise capacity did not return to the basal level. NR mice showed the highest food intake, lowest feed efficiency, increased oxygen consumption during the light (rest) cycle, increased physical activity during the dark (active) cycle, and increased heat production during both cycles. These variations were observed in the absence of changes in food intake and fecal parameters; however, NR fecal lipid content was lower, and the NR fecal microbiome profile was characterized by reduced abundance of Actinobacteria. Taken together, our findings suggest that NR mice showed an increased ability to metabolize excessive dietary fats in skeletal muscle at the expense of reduced exercise capacity that persisted for the duration of the study. These findings underscore the need for further comprehensive investigations into the mechanisms of obesity resistance, as they hold potential implications for weight-loss strategies in human subjects.

Voluntary exercise improves pulmonary inflammation through NF-κB and Nrf2 in type 2 diabetic male rats.

This study aimed to evaluate the effects of voluntary exercise as an anti-inflammatory intervention on the pulmonary levels of inflammatory cytokines in type 2 diabetic male rats. Twenty-eight male Wistar rats were divided into four groups (n=7), including control (Col), diabetic (Dia), voluntary exercise (Exe), and diabetic with voluntary exercise (Dia+Exe). Diabetes was induced by a high-fat diet (4 weeks) and intraperitoneal injection of streptozotocin (35 mg/kg), and animals did training on the running wheel for 10 weeks as voluntary exercise. Finally, the rats were euthanized and the lung tissues were sampled for the evaluation of the levels of pulmonary interleukin (IL)-10, IL-11, and TNF-α using ELISA, and the protein levels of Nrf-2 and NF-κB using western blotting and tissue histopathological analysis. Diabetes reduced the IL-10, IL-11, and Nrf2 levels (P<0.001 to P<0.01) and increased the levels of TNF-α and NF-κB compared to the Col group (P<0.001). Lung tissue levels of IL-10, IL-11, and Nrf2 in the Dia+Exe group enhanced compared to the Dia group (P<0.001 to P<0.05), however; the TNF-α and NF-κB levels decreased (P<0.001). The level of pulmonary Nrf2 in the Dia+Exe group was lower than that of the Exe group while the NF-κB level increased (P<0.001). Moreover, diabetes caused histopathological changes in lung tissue which improved with exercise in the Dia+Exe group. These findings showed that voluntary exercise could improve diabetes-induced pulmonary complications by ameliorating inflammatory conditions.

Exercise leads to sex-specific recovery of behavior and pathological AD markers following adolescent ethanol exposure in the TgF344-AD model.

Human epidemiological studies suggest that heavy alcohol consumption may lead to earlier onset of Alzheimer's Disease (AD), especially in individuals with a genetic predisposition for AD. Alcohol-related brain damage (ARBD) during a critical developmental timepoint, such as adolescence, interacts with AD-related pathologies to accelerate disease progression later in life. The current study investigates if voluntary exercise in mid-adulthood can recover memory deficits caused by the interactions between adolescence ethanol exposure and AD-transgenes. Male and female TgF344-AD and wildtype F344 rats were exposed to an intragastric gavage of water (control) or 5 g/kg of 20% ethanol (adolescent intermittent ethanol; AIE) for a 2 day on/off schedule throughout adolescence (PD27-57). At 6 months old, rats either remained in their home cage (stationary) or were placed in a voluntary wheel running apparatus for 4 weeks and then underwent several behavioral tests. The number of cholinergic neurons in the basal forebrain and measure of neurogenesis in the hippocampus were assessed. Voluntary wheel running recovers spatial working memory deficits selectively in female TgF344-AD rats exposed to AIE and improves pattern separation impairment seen in control TgF344-AD female rats. There were sex-dependent effects on brain pathology: Exercise improves the integration of recently born neurons in AIE-exposed TgF344-AD female rats. Exercise led to a decrease in amyloid burden in the hippocampus and entorhinal cortex, but only in male AIE-exposed TgF344-AD rats. Although the number of basal forebrain cholinergic neurons was not affected by AD-transgenes in either sex, AIE did reduce the number of basal forebrain cholinergic neurons in female rats. These data provide support that even after symptom onset, AIE and AD related cognitive decline and associated neuropathologies can be rescued with exercise in unique sex-specific ways.