Voluntary Physical Activity Research Articles

AXIOLOGICAL ASPECTS OF EDUCATION OF RECREATIONAL CULTURE OF STUDENT YOUTH

The article reveals the problems of attracting modern student youth to the cultural forms of leisure organization and presents the education of young people and girls of recreational culture as one of the means of activating this process. Recreational student culture is seen as voluntary physical activity using physical exercises aimed at improving psycho-physiological performance; entertainment and versatile improvement of students' personality in the process of vocational training; as one of the functions of culture related to the restoration of one's spiritual powers, the renewal and the restoration of one's spiritual potential, and the like. Health is the leading value in most definitions, the preservation and restoration of which serves the purpose of recreational activity. The author analyzes two groups of factors of low recreational culture of the modern Ukrainian student (mental-environmental and factor of unrecognized value) and outlines ways of its upbringing on value basis.

Voluntary wheel running promotes myelination in the motor cortex through Wnt signaling in mice

Myelin of the central nervous system exhibits strong plasticity, and skill learning exercise promotes oligodendrogenesis and adaptive myelination. Increasing evidence shows that brain structures and functions are affected by physical activity. However, the impact of voluntary physical activity on central myelination and its underlying mechanism remains unclear. The present study aimed to investigate the effect of voluntary wheel running (VWR) on central oligodendrogenesis and adaptive myelination in mice. Adult C57BL/6 J mice were placed in running wheels and allowed for voluntary running 2 weeks. Myelin levels in the central nervous system were detected using western blotting, qRT-PCR, immunohistochemical staining, and electron microscopy. Oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) were detected using immunohistochemical staining and 5-bromo-2-deoxyuridine (BrdU) assays. Motor abilities of the animals were examined using open-field, rotarod running, and beam-walking behavioral paradigms. Vital molecules of Wnt signaling were detected, and the involvement of such molecules was verified using in vitro culture of OPCs. Our results showed that VWR significantly enhanced the myelination in the motor cortex. VWR promoted the proliferation and differentiation of OPCs, and the maturation of OLs. The VWR-regulated myelination was associated with the improved motor skill and decreased mRNA level of Wnt3a/9a, whereas stimulation of Wnt signaling pathway with Wnt3a or Wnt9a suppressed OPCs proliferation and differentiation in vitro. The present study demonstrated that physical activity is highly efficient at promoting myelination in the motor cortex, by enhancing the proliferation of OPCs and accelerating the generation of myelin, providing a step forward in understanding the beneficial effects of physical activity on central myelination and its underlying mechanism.

Muscle-Specific Sensitivity to Voluntary Physical Activity and Detraining.

Aerobic physical activity triggers adaptations in skeletal muscle including a fast-to-slow shift in myosin heavy chain (MHC) isoforms, an enhanced capillary network, and mitochondrial biogenesis to meet increased demands placed upon this tissue. Although the magnitude of these responses appears to be dependent on muscle phenotype as well as training volume and/or intensity, the whole-muscle response to detraining remains mostly unexplored. Here, we hypothesized that the shifts toward slower MHC phentotype and the increased capillarity and mitochondrial oxidative markers induced with training would return toward sedentary (SED) control levels sooner in the fast plantaris than in the slow soleus muscle as a result of detraining. Soleus and plantaris muscles from 8-week (TR 8wk) voluntarily running adult female Sprague–Dawley rats were compared to muscles from SED and detrained rats (DETR) (4 weeks voluntary running followed by 4 weeks of reduced activity), which were subdivided into low- (DETR Lo) and high-running-distance (DETR Hi) groups. We show that maintaining the fast-to-slow MHC isoform shift required consistent aerobic training in the soleus and plantaris muscles: detraining clearly abolished any fast-to-slow gains in the plantaris, whereas the training volume in DETR Hi rats appeared to influence the MHC return to basal levels in the soleus. Total capillary number (per mm2) in the plantaris increased in all groups compared to SED levels, but, in the soleus, this enhancement was observed only in the TR 8wk rats. Generally, increased mitochondrial markers for aerobicitiy were observed in TR 8wk plantaris, but not soleus, muscles. In a second experiment, we show that the muscle-specific adaptations were similar after 4 weeks of voluntary exercise (TR 4wk) as in 4 weeks (TR 8wk). Taken together, our findings suggest that the plantaris muscle is more sensitive to voluntary physical activity and detraining than the soleus muscle; these results also demonstrate that the soleus muscle requires a greater aerobic challenge (i.e., intensity, duration) to trigger phenotypic, angiogenic, or aerobic enzyme adaptations. Our findings generally suggest that muscular aerobic fitness to voluntary running, or its loss during detraining, manifests as changes occurring primarily within fast, rather than slow, muscle phenotypes.

Voluntary wheel running during adolescence distinctly alters running output in adulthood in male and female rats

Adult female rats show greater running output compared with age-matched male rats, and the midbrain dopaminergic system may account for behavioral differences in running output. However, it is unknown if the lower running output in adult males can be regulated by wheel running experience during adolescence, and whether wheel running experience during adolescence will diminish the sex differences in running output during adulthood. We therefore determined and compared the exercise output in adult male and female rats that either had initiated voluntary wheel running only during adulthood or during adolescence. Our results demonstrate that running output in adult males were significantly higher when running was initiated during adolescence, and this higher running output was not significantly different from females. Running output did not differ during adulthood in females when wheel running was initiated during adolescence or during adulthood. Higher running output in females was associated with reduced expression of tyrosine hydroxylase and hyperactivation of calcium/calmodulin-dependent protein kinase II (CaMKII) in the dorsal striatum. Notably, running during adolescence-induced higher exercise output in adult males was associated with hyperactivation of CaMKII in the dorsal striatum, indicating a mechanistic role for CaMKII in running output. Together, the present results indicate sexually dimorphic adaptive biochemical changes in the dorsal striatum in rats that had escalated running activity, and highlight the importance of including sex as a biological variable in exploring neuroplasticity changes that predict enhanced exercise output in a voluntary physical activity paradigm.

Voluntary physical activity counteracts Chronic Heart Failure progression affecting both cardiac function and skeletal muscle in the transgenic Tgαq*44 mouse model.

Physical activity is emerging as an alternative nonpharmaceutical strategy to prevent and treat a variety of cardiovascular diseases due to its cardiac and skeletal muscle beneficial effects. Oxidative stress occurs in skeletal muscle of chronic heart failure (CHF) patients with possible impact on muscle function decline. We determined the effect of voluntary‐free wheel running (VFWR) in preventing protein damage in Tgαq*44 transgenic mice (Tg) characterized by a delayed CHF progression. In the early (6 months) and transition (12 months) phase of CHF, VFWR increased the daily mean distance covered by Tg mice eliminating the difference between Tg and WT present before exercise at 12 months of age (WT Pre‐EX 3.62 ± 1.66 vs. Tg Pre‐EX 1.51 ± 1.09 km, P < 0.005; WT Post‐EX 5.72 ± 3.42 vs. Tg Post‐EX 4.17 ± 1.8 km, P > 0.005). This effect was concomitant with an improvement of in vivo cardiac performance [(Cardiac Index (mL/min/cm2): 6 months, untrained‐Tg 0.167 ± 0.005 vs. trained‐Tg 0.21 ± 0.003, P < 0.005; 12 months, untrained‐Tg 0.1 ± 0.009 vs. trained‐Tg 0.133 ± 0.005, P < 0.005]. Such effects were associated with a skeletal muscle antioxidant response effective in preventing oxidative damage induced by CHF at the transition phase (untrained‐Tg 0.438 ± 0.25 vs. trained‐Tg 0.114 ± 0.010, P < 0.05) and with an increased expression of protein control markers (MuRF‐1, untrained‐Tg 1.12 ± 0.29 vs. trained‐Tg 14.14 ± 3.04, P < 0.0001; Atrogin‐1, untrained‐Tg 0.9 ± 0.38 vs. trained‐Tg 7.79 ± 2.03, P < 0.01; Cathepsin L, untrained‐Tg 0.91 ± 0.27 vs. trained‐Tg 2.14 ± 0.55, P < 0.01). At the end‐stage of CHF (14 months), trained‐Tg mice showed a worsening of physical performance (decrease in daily activity and weekly distance and time of activity) compared to trained age‐matched WT in association with oxidative protein damage of a similar level to that of untrained‐Tg mice (untrained‐Tg 0.62 ± 0.24 vs. trained‐Tg 0.64 ± 0.13, P > 0.05). Prolonged voluntary physical activity performed before the onset of CHF end‐stage, appears to be a useful tool to increase cardiac function and to reduce skeletal muscle oxidative damage counteracting physical activity decline.

Maternal physical activity-induced adaptive transcriptional response in brain and placenta of mothers and rat offspring.

Maternal physical activity induces brain functional changes and neuroplasticity, leading to an improvement of cognitive functions, such as learning and memory in the offspring. This study investigated the effects of voluntary maternal physical activity on the gene expression of the neurotrophic factors (NTFs): BDNF, NTF4, NTRK2, IGF-1 and IGF-1r in the different areas of mother's brain, placenta and foetus brain of rats. Female Wistar rats (n = 15) were individually housed in voluntary physical activity cages, containing a running wheel, for 4 weeks (period of adaptation) before gestation. Rats were classified as inactive (I, n = 6); active (A, n = 4) and very active (VA, n = 5) according to daily distance spontaneously travelled. During gestation, the dams continued to have access to the running wheel. At the 20th day of gestation, gene expression of NTFs was analysed in different areas of mother's brain (cerebellum, hypothalamus, hippocampus and cortex), placenta and the offspring's brain. NTFs gene expression was evaluated using quantitative PCR. Very active mothers showed upregulation of IGF-1 mRNA in the cerebellum (36.8%) and NTF4 mRNA expression in the placenta (24.3%). In the cortex, there was a tendency of up-regulation of NTRK2 mRNA (p = 0.06) in the A and VA groups when compared to I group. There were no noticeable changes in the gene expression of NTFs in the offspring's brain. Our findings suggest the existence of a developmental plasticity induced by maternal physical activity in specific areas of the brain and placenta representing the first investment for offspring during development.

Physical exercise positively modulates DOX-induced hepatic oxidative stress, mitochondrial dysfunction and quality control signaling

Doxorubicin (DOX), a widely used and efficient antineoplastic agent, is mainly limited by cardiotoxicity, although other tissues including liver are also affected. The effects of exercise to cope with DOX side-effects has already been studied in the heart and brain, demonstrating successful results. However, the benefits of this non-pharmacological strategy have not been so extensively checked in the liver. We here aimed to ascertain whether exercise could mitigate DOX-induced liver harmful effects using mitochondria as a model for evaluating toxicity.Twenty-four male rats were divided into four groups: SED + SAL (sedentary with saline administration), SED + DOX (sedentary with DOX administration), ET + DOX (endurance-trained with DOX administration) and VPA + DOX (voluntary physical activity with DOX administration). Isolated liver mitochondria were obtained for evaluation of their respiratory activity and transmembrane electrical potential endpoints. Molecular markers of oxidative damage (carbonyls, MDA, aconitase, MnSOD), mitochondrial dynamics (PGC-1α, TFAM, OPA1, DRP1, MFN1) and auto(mito)phagy signaling (p62, LC3, Beclin1, Bcl-2, PINK, Parkin) were measured. Transmission electron microscopy evaluation was used to analyze mitochondrial morphological alterations.When compared to SED + SAL, respiratory function of SED + DOX was compromised. Decreased SOD and aconitase activities and increased MDA content, decreases in PGC-1α, TFAM, OPA1 and MFN1 expressions, and increases in DRP1 and LC3II/LC3I ratio were also observed after DOX administration. However, these alterations were reverted or mitigated in the ET + DOX group. Semi-quantitative and qualitative analyses from microphotographs showed that liver mitochondria of SED + DOX animals were more circular and had lower density, whereas the animals with exercise showed a tendency to revert this phenotype and increase the mitochondrial density.Taken together, our results suggest that physical exercise, particularly ET, positively reversed the deleterious effects caused by DOX administration, such as oxidative damage, mitochondrial dysfunction, and altered mitochondrial dynamics toward fission, thus contributing to increase liver resistance against DOX administration.

Aerobic Exercise Reduced Body Weight through Midbrain-striatal Dopaminergic Plasticity in Obese Mice

PURPOSE: Previous research indicates that midbrain-striatal dopaminergic disruption is associated with obesity and involved in feeding behavior and voluntary physical activity. Since the action of exercise on midbrain-striatal dopamine, it may be an effective strategy to improve physical inactivity and overeating induced by food reward dysfunction in obesity. We therefore explored the mechanisms. METHODS: Male C57BL/6 mice were randomly divided into control group (C, n=12), exercise group(CE, n=12)fed a normal diet (13% fat), and an additional group (H, n=40) fed a high fat diet (51% fat). Obese mice in H were further divided into obesity group (O, n=12) and obesity + exercise group (OE, n=12). The CE and OE mice underwent treadmill exercise (5-13 m/min, about 58%-75% VO2max, 50 min/d, 5 d/wk for 8 wks). The food preference test and open-field test were used to assess food reward, and voluntary physical activity. Tyrosine hydroxylase (TH)+ neurons were detected by immunohistochemistry, and the expression of TH protein in midbrain-striatum were measured by western blot. RESULTS: Body weight of OE was 15.2% lower than that of O (P < 0.01). Sucrose preference, physical activity level and time were decreased by 25.8%, 46.77% and 37.56% in O compare to C (P < 0.05, P < 0.01, P < 0.01), but were 18.2%, 37.28% and 26.35% higher, respectively, in OE than O (P < 0.05). TH+ cells in substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) decreased by 15.41% and 18.45%, respectively, in O compare to C (P < 0.05), but increased by 12.62% and 15.53% in OE compare to O (P < 0.05). TH+ fibers in dorsal striatum nucleus accumbens were 16.36% and 17.48% lower in O than C (P < 0.05), but was 12.54% and 14.13% higher in OE vs. O (P < 0.05). In addition, the expression of TH protein in midbrain and striatum decreased by 18.46% (P < 0.05) and 16.35% (P < 0.05) in O compared with C, but increased by 12.23% and 11.58% in OE compare to O (P < 0.05). CONCLUSIONS: The aerobic exercise inhibits body weight gain, improves food reward and voluntary physical activity in obese mice. The exercise-induced midbrain-striatal dopaminergic plasticity may be one of the important mechanisms for this adaptation.

Rats Selectively Bred for High Voluntary Physical Activity Behavior are Not Protected from the Deleterious Metabolic Effects of a Western Diet When Sedentary

ABSTRACTBackgroundPhysical activity and diet are well-established modifiable factors that influence chronic disease risk. We developed a selectively bred, polygenic model for high and low voluntary running (HVR and LVR, respectively) distances. After 8 generations, large differences in running distance were noted. Despite these inherent behavioral differences in physical activity levels, it is unknown whether HVR rats would be inherently protected from diet-induced metabolic dysfunction.ObjectivesThe aim of this study was to determine whether HVR rats without voluntary running wheels would be inherently protected from diet-induced metabolic dysfunction.MethodsYoung HVR, LVR, and a wild-type (WT) control group were housed with no running wheel access and fed either a normal diet (ND) or a high-sugar/fat Western diet (WD) for 8 wk. Body weight, percentage body fat (by dual-energy X-ray absorptiometry scan), blood lipids [total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TGs), nonesterified fatty acids], and hepatic TG content were measured, and indices of insulin sensitivity were determined via an intravenous glucose tolerance test. Additionally, weekly energy intake and feed efficiency were calculated.ResultsAfter 8 wk, significant differences in body weight and body fat percentage were noted in all WD animals compared with ND animals, with the LVR-WD exhibiting the greatest increase due, in part, to their enhanced feed efficiency. Lipid dysregulation was present in all WD rat lines compared with ND counterparts. Furthermore, LVR-WD rats had higher total cholesterol, HDL cholesterol, and TG concentrations, and higher areas under the curve (AUC) for insulin than HVR-WD and WT-WD, although HVR-WD animals had higher AUCglucose than both LVR-WD and WT-WD and higher LDL than WT-WD.ConclusionsIn the absence of high voluntary running behavior, the genetic predisposition for high running in HVR did not largely protect them from the deleterious effects of a WD compared with LVR, suggesting genetic factors influencing physical activity levels may, in part, be independent from genes influencing metabolism.

Whole-Body ARHGAP21-Deficiency Improves Energetic Homeostasis in Lean and Obese Mice.

Inhibition of Rab-GAP TBC1 domain family member 1 (TBC1D1) reduces body weight and increases energy expenditure in mice. Here, we assessed the possible involvement of GTPase activating protein 21 (ARHGAP21), a Rho-GAP protein, in energy homeostasis. Wild-type and whole-body ARHGAP21-haplodeficient mice were fed either chow or high-fat diet for 10 weeks. These mice were analyzed for body weight, food intake, voluntary physical activity, and energy expenditure by indirect calorimetry. Real-time PCR was performed to determine changes in the expression of hypothalamic-anorexic genes. Whole-body ARHGAP21-haplodeficient mice showed lower body weight and food intake associated with increased energy expenditure. These mice also showed higher expression of hypothalamic-anorexic genes such as POMC and CART. Our data suggest that the reduction in body weight of ARHGAP21-haplodeficient mice was related to alterations in the central nervous system. This suggests a new role for ARHGAP21 in energetic metabolism and prompts us to consider GAP protein members as possible targets for the prevention and treatment of obesity and related diseases.

Regular Aerobic Voluntary Exercise Increased Oxytocin in Female Mice: The Cause of Decreased Anxiety and Increased Empathy-Like Behaviors

Background:It is known that regular physical activity reduces anxiety. Low anxiety levels affect mood, emotions, and empathy. Oxytocin is a powerful hormone that regulates social interaction, sexual reproduction, maternal–infant bonding, milk release, empathy, and anxiety. Empathy is an important behavior in the living community; and also important for sportsmen during sportive competition and daily living life, because sportsmen are also role model of people.Aims:To investigate the effects of voluntary physical activity on oxytocin, anxiety, and empathy levels as well as the relationship between them.Study Design:Animal experiment.Methods:Male and female mice were made to exercise in running wheel cages for 6 weeks. Their empathy and anxiety levels were evaluated by using Helping Behavior test and elevated plus maze and open field test, respectively. And then the brain and blood oxytocin levels were measured.Results:Empathy-like behavior was improved in both genders of the exercise groups (door-opening time decreased in both genders of exercise groups, p for both=0.0001). As a response to exercise, both the brain and serum oxytocin levels increased in female mice (both of p=0.0001); however, in males, oxytocin levels increased in only the brain (p<0.05). Anxiety levels decreased in all the exercise groups (increased time spent in the middle area of open field test, both genders, p=0.002; increased time spent in the open arms of elevated plus maze test, females p=0.004, males p=0.0001). There was a strong negative correlation between serum oxytocin levels and door opening time of helping behavior equipment, and moderate negative correlation was found between the brain oxytocin levels and door-opening time of helping behavior equipment in females. However, there was no correlation between both the brain and serum oxytocin levels and empathy behavior in males. But there were very strong positive correlations between low anxiety indicators and both the brain and serum oxytocin levels in both the genders.Conclusion:Voluntary physical activity decreases anxiety and increases empathy-like behavior in mice; which is associated with increased oxytocin levels in female mice but not in male mice. Further research is required to investigate the mechanisms of exercise effect on anxiety and empathic brain pathways in males.

The Effect of Growth Restriction on Voluntary Physical Activity Engagement in Mice.

The purpose of this study was to determine the effect of growth restriction on the biological regulation of physical activity. Using a cross-fostering, protein-restricted nutritive model, mice were growth-restricted during either gestation (GUN; N = 3 litters) or postnatal life (PUN; N = 3 litters). At 21 d of age, all mice pups were weaned and fed a nonrestrictive healthy diet for the remainder of the study. At 45 d of age, mice were individually housed in cages with free moving running wheels to assess physical activity engagement. At day 70, mice were euthanized, and the nucleus accumbens was analyzed for dopamine receptor 1 expression. Skeletal muscle fiber type and cross-sectional area of the soleus, extensor digitorom longus, and diaphragm were analyzed by immunohistochemistry. The soleus from the other hindleg was evaluated for calsequestrin 1 and annexin A6 expression. The PUN female mice (15,365 ± 8844 revolutions per day) had a reduction (P = 0.0221) in wheel revolutions per day as compared with the GUN (38,667 ± 8648 revolutions per day) and CON females (36,421.0 ± 6700 revolutions per day). The PUN female mice also expressed significantly higher dopamine receptor 1 compared (P = 0.0247) to the other groups. The PUN female soleus had a higher expression of calsequestrin 1, along with more type IIb fibers (P = 0.0398). Growth restriction during lactation reduced physical activity in female mice by reducing the central drive to be active and displayed a more fatigable skeletal muscle phenotype.

Voluntary wheel running effects on intra-accumbens opioid driven diet preferences in male and female rats

Palatability driven feeding and voluntary physical activity are mediated by and influence similar neural mechanisms, notably through the actions of opioids within the nucleus accumbens. Recent studies suggest that access to a voluntary running wheel results in sex dependent behavioral and physiological adaptations related to opioid mediated palatability-driven feeding. To explore this relationship, male and female Wistar rats were given either access to a voluntary running wheel (RUN group) or no access (SED group) for one week prior to being stereotaxically implanted with bilateral cannulae targeting the nucleus accumbens. Following 7 days of recovery, with RUN or SED conditions continuing the duration of the experiment, all rats were assessed daily (2 h/day) for feeding behavior of concurrently accessible high-carbohydrate and high-fat diet for one week. Following this week, all rats were administered the μ-opioid receptor agonist D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO) (0.0025 μg, 0.025 μg, or 0.25 μg/0.5 μl/side) or the opioid antagonist naloxone (20 μg/0.5 μl/side) into the nucleus accumbens and given concurrent access (2 h) to both diets. All groups expressed a significant baseline preference for the high-carbohydrate diet. DAMGO administration, compared to saline treatment, led to significant increased consumption of the high-carbohydrate diet in all treatment groups. While high-fat diet consumption also increased following DAMGO administration, the influence of DAMGO was much more robust for the preferred high-carbohydrate diet in all groups. Compared to males, females consumed significantly more of both diets at baseline and following DAMGO treatment. Both male and female rats in the RUN condition consumed more high-carbohydrate diet compared to rats in the SED condition. While males exhibited similar increased consumption of both diets regardless of RUN or SED condition, females in the RUN condition displayed a greater sensitivity to DAMGO-driven consumption of the preferred high-carbohydrate, compared to SED females.

From clock to functional pacemaker.

In mammals, the central pacemaker that coordinates 24‐hr rhythms is located in the suprachiasmatic nucleus (SCN). Individual neurons of the SCN have a molecular basis for rhythm generation and hence, they function as cell autonomous oscillators. Communication and synchronization among these neurons are crucial for obtaining a coherent rhythm at the population level, that can serve as a pace making signal for brain and body. Hence, the ability of single SCN neurons to produce circadian rhythms is equally important as the ability of these neurons to synchronize one another, to obtain a bona fide pacemaker at the SCN tissue level. In this chapter we will discuss the mechanisms underlying synchronization, and plasticity herein, which allows adaptation to changes in day length. Furthermore, we will discuss deterioration in synchronization among SCN neurons in aging, and gain in synchronization by voluntary physical activity or exercise.

Beneficial Effects of Voluntary Wheel Running in an Endometriosis Animal Model

Endometriosis is a chronic gynecological disorder defined as the presence of endometrial glands and stroma outside the endometrial cavity. This condition is characterized by peritoneal inflammation, fibrosis, adhesions and ovarian cysts, which result in chronic pelvic pain, painful periods and infertility. Our previous studies have demonstrated that exposure to stress and modulation of the hypothalamic pituitary axis exacerbates the development and severity of endometriosis. A physically active lifestyle has been shown to confer health benefits in many chronic conditions by potentially acting as a stress buffer. However, no experimental data exist regarding the impact of exercise on the course of endometriosis.HypothesisPhysical exercise can ‘realign/reset’ dysregulation of the brain‐gut axis resulting in reduced endometriosis symptoms in an animal model.MethodsEndometriosis was induced in female Sprague Dawley rats by implanting uterine tissue next to the intestinal mesentery on day 0. Sham controls received sutures only. One group of endometriosis animals had access to a running wheel for 2 weeks prior to endometriosis induction until time of sacrifice at day 60 (EEX; n=6). Sham controls (Sham; n=5) and Endo (n=6) received no exercise. Anxiety was measured using open field and zero maze 1 week after surgery and at time of sacrifice. All animals were examined for developed vesicles which were collected and measured. Colon and uterine tissue were analyzed for damage and myeloperoxidase (MPO) levels. Brain, liver, spleen, adrenal glands, leg muscles and fat were collected and stored for future analysis.ResultsEndo animals developed vesicles in 82.61% of the implants with an average total area of 50.27±9.48mm2 and weight of 0.053±0.006g per animal. These animals also had significantly increased macroscopic colonic damage compared to Sham (p&lt;0.0001). Exposure to exercise significantly decreased the number of vesicles that developed (54.17%; p&lt;0.05), as well as their size (20.25±5.84mm2, p&lt;0.05) and weight (0.035±0.005g, p&lt;0.05), although no significant differences in anxiety were noted between the groups. EEX also had less macroscopic (p&lt;0.05) and microscopic colonic damage, with no significant difference in MPO. EEX had higher levels of lactoferrin, known to be a natural immunomodulator, which tended to inversely correlate with lesion size. Adrenal glands tended to be smaller in Endo compared to Sham, whereas EEX had significantly larger adrenal glands/body weight than Endo alone (p&lt;0.05).ConclusionsOur results suggest that voluntary physical activity might protect against endometriosis and alleviate the associated symptomatology via immune modulation of the brain‐gut axis. This offers the potential for further exploration of this complementary therapy in the patient population.Support or Funding InformationSupported in part by P20GM103475‐16 &amp; R15AT009915This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The androgen receptor in the hypothalamus positively regulates hind-limb muscle mass and voluntary physical activity in adult male mice

We have previously shown that expression of the androgen receptor (AR) in neurons within the brain positively regulates hind-limb muscle mass and physical activity in male mice. To further investigate the region of the brain responsible for mediating these effects of testosterone and to determine whether they are only important for muscle mass accrual during development or whether they are also important for the maintenance of muscle mass in the adult, we deleted the AR specifically in the hypothalamus of adult male mice (Hyp-ARKOs). Hyp-ARKO mice were generated by bilateral stereotaxic microinjection of an adeno-associated virus (AAV) expressing GFP and iCre recombinase under the control of the e-synapsin promoter into the hypothalamus of 10-week-old exon 3-AR floxed male mice. AR mRNA was deleted by 45% in the hypothalamus of Hyp-ARKOs at 5 weeks post-AAV-eSyn-iCre injection. This led to an increase in the mass of the androgen-dependent organs, seminal vesicles and kidneys, by 30% (P < 0.01) and 10% (P < 0.05) respectively, and an increase in serum luteinizing hormone (LH) by 2 fold (P < 0.05). Whilst the mean value for serum testosterone was higher in the Hyp-ARKOs, this did not reach statistical significance. Despite a phenotype consistent with increased androgen bioactivity in Hyp-ARKOs, which would be expected to increase muscle mass, the mass of the hind-limb muscles, gastrocnemius (Gast) (P = 0.001), extensor digitorum longus (EDL) (P < 0.001) and soleus (Sol) (P < 0.01) were paradoxically decreased by 12–19% compared to controls. Voluntary physical activity was reduced by 65% (P < 0.05) in Hyp-ARKO male mice and was associated with a reduction in gene expression of Drd1a and Maob (P ≤ 0.05) in the hypothalamus, suggesting involvement of the brain dopaminergic system. These data provide compelling evidence that androgen signalling via the AR in the hypothalamus acts to positively regulate the maintenance of hind-limb muscle mass and voluntary activity in adult male mice, independent of AR signalling in peripheral tissues.

ISSLS Prize in Basic science 2019: Physical activity attenuates fibrotic alterations to the multifidus muscle associated with intervertebral disc degeneration.

Chronic low back pain causes structural remodelling and inflammation in the multifidus muscle. Collagen expression is increased in the multifidus of humans with lumbar disc degeneration. However, the extent and mechanisms underlying the increased fibrotic activity in the multifidus are unknown. Physical activity reduces local inflammation that precedes multifidus fibrosis during intervertebral disc degeneration (IDD), but its effect on amelioration of fibrosis is unknown. This study aimed to assess the development of fibrosis and its underlying genetic network during IDD and the impact of physical activity. Wild-type and SPARC-null mice were either sedentary or housed with a running wheel, to allow voluntary physical activity. At 12months of age, IDD was assessed with MRI, and multifidus muscle samples were harvested from L2 to L6. In SPARC-null mice, the L1/2 and L3/4 discs had low and high levels of IDD, respectively. Thus, multifidus samples from L2 and L4 were allocated to low- and high-IDD groups compared to assess the effects of IDD and physical activity on connective tissue and fibrotic genes. High IDD was associated with greater connective tissue thickness and dysregulation of collagen-III, fibronectin, CTGF, substance P, TIMP1 and TIMP2 in the multifidus muscle. Physical activity attenuated the IDD-dependent increased connective tissue thickness and reduced the expression of collagen-I, fibronectin, CTGF, substance P, MMP2 and TIMP2 in SPARC-null animals and wild-type mice. Collagen-III and TIMP1 were only reduced in wild-type animals. These data reveal the fibrotic networks that promote fibrosis in the multifidus muscle during chronic IDD. Furthermore, physical activity is shown to reduce fibrosis and regulate the fibrotic gene network. These slides can be retrieved under Electronic Supplementary Material.

Effect of physical activity on structural asymmetry of mouse hippocampus

The relevance of studies of adult neurogenesis is evident in connection with the potential use of these new neurons to replace neurons lost in the process of life. Despite considerable efforts, little is known about the fnal fate of these cells, the functional signifcance of their connections and the regulation of their development. It is known that physical activity signifcantly increases the number of fssile progenitors, the precursors of new neurons in the dentate gyrus of the hippocampus. The existing immunohistochemical methods for labeling new neurons do not allow tracing the temporal dynamics of changes in the volume of brain structures in the same animal, induced by external impacts, such as voluntary exercise. This makes it an urgent task to develop and improve methods for long­term control of changes that occur in the adult hippocampus due to the induction of neurogenesis. The main purpose of this work was to non­invasively track, by using magnetic resonance imaging (MRI), the temporal dynamics of changes in the volume of the hippocampus in the same animals that had voluntary physical activity. It was found that voluntary exercise did not change the total volume of the mouse hippocampus. However, the difference in the volume ratio between the right and left parts of the hippocampus was signifcantly lower compared with the control group. The reconstruction and analysis of protein­protein interactions that ensure the survival of a large number of new neurons and their integration into existing neural networks in the hippocampus have been carried out. The proposed approach allows the non­invasive registration of changes in the ratio of the volumes of these paired brain structures.

Effect of NAC treatment and physical activity on neuroinflammation in subchronic Parkinsonism; is physical activity essential?

BackgroundNeuroprotective strategies are becoming relevant to slow down dopaminergic cell death and inflammatory processes related to the progressive neurodegeneration in Parkinson’s disease (PD). Interestingly, among others, physical activity (PA) or anti-oxidant agents (such as N-acetyl-L-cysteine, NAC) are common therapeutic strategies. Therefore, this study aims to analyze if there is a synergistic effect of physical activity along with NAC treatment on dopaminergic degeneration and neuroinflammatory response in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism model after subchronic intoxication.MethodsTo ascertain this possibility, 48 8-week-old male mice (C57BL/6 strain) were used. Twenty four of them were placed individually in cages where voluntary physical activity was automatically monitored during 30 days and were divided into groups: (i) control; (ii) NAC; (iii) MPTP, and (iv) MPTP+NAC. The other 24 mice were divided into the same four groups but without physical activity.ResultsThe data collected during the treatment period showed that there was an overall increase in the total running distance in all groups under physical activity, including Parkinsonian animals. However, the monitoring data per day showed that the activity routine by MPTP and MPTP+NAC groups was disrupted by alterations in the circardian rhythm because of MPTP intoxication. Results from post-mortem studies in the substantia nigra pars compacta (SNpc) showed significant decrease in the number of TH+ cells in all MPTP groups. Moreover, TH+ expression in the striatum was significantly decreased in all MPTP groups. Thus, PA + NAC treatment do not protect dopaminergic neurons against a subchronic intoxication of MPTP. Regarding glial response, the results obtained from microglial analysis do not show significant increase in the number of Iba-1+ cell in MPTP+NAC and MPTP+PA + NAC. In the striatum, a significant decrease is observed only in the MPTP+NAC group compared with that of the MPTP group. The microglial results are reinforced by those obtained from the analysis of astroglial response, in which a decrease in the expression of GFAP+ cells are observed in MPTP+NAC and MPTP+PA + NAC compared with MPTP groups both in the SNpc and in the striatum. Finally, from the study of the astroglial response by the co-localization of GFAP/S100b, we described some expression patterns observed based on the severity of the damage produced by the MPTP intoxication in the different treated groups.ConclusionsThese results suggest that the combination of physical activity with an anti-oxidant agent does not have a synergistic neuroprotective effect in the nigrostriatal pathway. Our results show a potential positive effect, only due to NAC treatment, on the neuroinflammatory response after subchronic MPTP intoxication. Thus, physical activity is not essential, under these conditions. However, we believe that physical activity, used for therapeutic purposes, has a beneficial long-term effect. In this line, these results open the door to design longer studies to demonstrate its promising effect as neuroprotective strategy.

Hooked on Exercise: The Relationship between Exercise Addiction and Healthy Adherence in Collegiate Student-Athletes

Introduction: Exercise addiction is a prevalent issue among NCAA student-athletes that is often undiagnosed. The effects of excessive exercise involvement include but are not limited to lack of recovery time, acquisition of overuse injuries, and development of eating disorders. In addition, exercise addiction can result in low athletic and academic performances, subsequent depression, and resistance to seek professional assistance. The study findings may aid athletic administration and coaching staff in developing appropriate training methods that would facilitate student-athletes’ healthy adherence to physical activity. Purpose: The purpose of the current study was to explore: a) the levels of Division I student-athletes’ physiological and psychological dependence on physical activity (exercise addiction); b) the frequency and duration of student-athletes’ voluntary physical activity, in addition to the NCAA required training time; c) the motivational factors behind student-athletes’ voluntary physical activity, and d) the relationship between student-athletes’ exercise dependence and their weekly hours of voluntary physical activity. Methods: In total, 106 NCAA Division I collegiate athletes completed the Exercise Dependence Scale (EDS-21) and reported the duration and frequency of physical activity performed in addition to the NCAA required training. Participants also indicated the motivating forces behind their voluntary physical activity. Multiple linear regression and ANOVA tests were conducted to establish statistical significance for the relationships of interest. Results: Findings indicated, out of 106 student-athletes, 14.2% of athletes were identified as exercise dependent, while 62.3% of athletes demonstrated withdrawal symptoms. Exercise dependent student-athletes engaged in up to 6 hours of weekly physical activity in addition to the required 20-hour physical training (M = 4.27, SD = 0.26). On the NCAA required day off, 63 student-athletes (59.43%) engaged in up to 2 hours of physical activity (M = 1.34, SD = 0.13). Improving athletic performance was the main motivation behind athletes’ voluntary physical activity. Further, the results of multiple linear regression and ANOVA revealed a strong positive relationship between student-athletes’ exercise dependence and their weekly hours of voluntary physical activity (F (1, 104) = 181.139, p R = 0.797). Thus, exercise dependent student-athletes engaged in much higher amounts of voluntary physical activity than symptomatic and asymptomatic student-athletes (Mean differences = 1.145 and 3.267 hours, respectively). Discussion: Athletic administration and coaching staff can shape athletes’ perceptions of healthy exercise habits and facilitate long-term healthy adherence to physical activity. Future research can examine the effectiveness of educational programs for exercise addiction prevention on student-athletes’ abilities to detect maladaptive exercise habits.