Sedentary Rats Research Articles

Os benefícios do exercício físico de alta intensidade antes e após a indução da doença de Parkinson em ratos

Abstract High-intensity physical activity is a non-pharmacological intervention that has been tested as a treatment for Parkinson’s disease (PD). The objective of the study was to investigate the benefits of high-intensity physical exercise on the number of neurons and astrocytes in a a rat model of Parkinson’s disease submitted to training before and after the inducing injury. Seventy Wistar rats were used, distributed as follows: nine rats trained before PD induction (DP-Exa), nine trained after PD induction (DP-Exd), 10 trained before and after PD induction (DP-Exad), and nine sedentary rats (DP-Sed). There were also the same groups but with the rats exposed to the sham surgery (control). High-intensity physical exercise on a vertical ladder was performed before and/or after PD induction for 5 days/week, 30-45 min a day, for 4 weeks. PD was induced with an electrolytic lesion (AP -4.9, ML 1.7, and DV 8.1). At the end of the experiment, the brain was removed for Nissl staining and immunohistochemistry of glial fibrillary acidid protein (GFAP) in the substantia nigra and striatum. The DP-Exa, Sham-Exa, DP-Exad, and Sham-Exad groups showed a greater number of neurons and higher expression of GFAP in the substantia nigra and stiatum compared with the the DP-Exd, Sham-Exd, DP-Sed, and Sham-Sed groups. Thus, rats that performed high-intensity training before or before and after PD induction had higher densities of neurons and astrocytes.

A novel genetic model provides a unique perspective on the relationship between postexercise glycogen concentration and increases in the abundance of key metabolic proteins after acute exercise.

Some acute exercise effects are influenced by postexercise (PEX) diet, and these diet-effects are attributed to differential glycogen resynthesis. However, this idea is challenging to test rigorously. Therefore, we devised a novel genetic model to modify muscle glycogen synthase 1 (GS1) expression in rat skeletal muscle with an adeno-associated virus (AAV) short hairpin RNA knockdown vector targeting GS1 (shRNA-GS1). Contralateral muscles were injected with scrambled shRNA (shRNA-Scr). Muscles from exercised (2-hour-swim) and time-matched sedentary (Sed) rats were collected immediately postexercise (IPEX), 5-hours-PEX (5hPEX), or 9-hours-PEX (9hPEX). Rats in 5hPEX and 9hPEX experiments were refed (RF) or not-refed (NRF) chow. Muscles were analyzed for glycogen, abundance of metabolic proteins (pyruvate dehydrogenase kinase 4, PDK4; peroxisome proliferator-activated receptor γ coactivator-1α, PGC1α; hexokinase II, HKII; glucose transporter 4, GLUT4), AMP-activated protein kinase phosphorylation (pAMPK), and glycogen metabolism-related enzymes (glycogen phosphorylase, PYGM; glycogen debranching enzyme, AGL; glycogen branching enzyme, GBE1). shRNA-GS1 versus paired shRNA-Scr muscles had markedly lower GS1 abundance. IPEX versus Sed rats had lower glycogen and greater pAMPK, and neither of these IPEX-values differed for shRNA-GS1 versus paired shRNA-Scr muscles. IPEX versus Sed groups did not differ for abundance of metabolic proteins, regardless of GS1 knockdown. Glycogen in RF-rats was lower for shRNA-GS1 versus paired shRNA-Scr muscles at both 5hPEX and 9hPEX. HKII protein abundance was greater for 5hPEX versus Sed groups, regardless of GS1 knockdown or diet, and despite differing glycogen levels. At 9hPEX, shRNA-GS1 versus paired shRNA-Scr muscles had greater PDK4 and PGC1α abundance within each diet group. However, the magnitude of PDK4 or PGC1α changes was similar in each diet group regardless of GS1 knockdown although glycogen differed between paired muscles only in RF-rats. In summary, we established a novel genetic approach to investigate the relationship between muscle glycogen and other exercise effects. Our results suggest that exercise-effects on abundance of several metabolic proteins did not uniformly correspond to differences in postexercise glycogen.

High intensity interval training exercise increases dopamine D2 levels and modulates brain dopamine signaling.

Previous research has outlined the health benefits of exercise including its therapeutic potential for substance use disorders (SUD). These data have already been utilized and it is now common to find exercise as part of SUD treatment and relapse prevention programs. However, we need to better understand different exercise regimens and determine which would be the most beneficial for SUDs. Recently, high intensity interval training (HIIT) has gained attention in comparison with aerobic and resistance exercise. Little is known regarding the neurobiological mechanisms of HIIT, including its effects on dopamine signaling and receptor levels in the brain. The present study examined the effects of chronic HIIT exercise on dopamine signaling as measured by dopamine type 1-like receptor (D1R)-like, dopamine type 2-like receptor (D2R)-like, and tyrosine hydroxylase (TH) quantification in the brains of male and female rats as measured by [3H] SCH 23390 and [3H] spiperone autoradiography, and TH-immunoreactive optical density values. Rats were separated in two groups: sedentary and HIIT exercise. Exercise was on a treadmill for 30 min daily (10 3 min cycles) for six weeks with progressive speed increased up to 0.8 mph (21.5 m/min). Results showed for D2R-like binding, a significant effect across the ventral caudate putamen (V CPU) between sexes, such that mean D2R-like binding was 14% greater for males than females. In the nucleus accumbens shell (Nac Shell), the HIIT Exercise rats showed 16% greater D2R-like binding as compared to the sedentary rats. No significant effects of HIIT exercise were found across groups for brain D1R-like binding levels or TH expression. These results suggest that HIIT exercise can modulate dopamine signaling by way of increased D2R. These findings support the premise that HIIT exercise plays an important role in dopamine signaling and, may provide a potential mechanism for how HIIT exercise can impact the brain and behavior.

Comparison of the effects of BDNF/TRKB signalling on metabolic biomarkers in the liver of sedentary and trained rats with normal and knockout BDNF genotypes.

Introduction: The effect of brain-derived neurotrophic factor (BDNF) on the modulation of metabolic processes in the liver is poorly understood. Therefore, the aim of this study was to investigate whether hepatic concentrations or activities of metabolic biomarkers depend on altered BDNF/TrkB content in the liver, resulting from different BDNF genotypes of rats. In addition, it was assessed whether 5-week moderate endurance training modifies the levels of BDNF/Trk-B signaling and studied hepatic markers. Methods: Experiments were performed on wild-type and heterozygous BDNF knockout (HET, SD-Bdnf) rats, which were divided into four groups: control with normal genotype (Bdnf+/+), control with BDNF knockout genotype (Bdnf+/-), trained with normal genotype (Bdnf+/+T) and trained with BDNF knockout genotype (Bdnf +/-T). BDNF/TrkB concentrations as well as selected metabolic biomarkers including lipids-total cholesterol (CHOL), low-density lipoprotein (LDL), triglycerides (TG); enzymes-alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP); hormones-insulin (INS) and leptin (LEPT) as well as interleukin-6 (IL-6) as regeneration indicator were measured directly in liver homogenates. Results and Discussion: The study showed that Bdnf+/- rats exhibited reduced BDNF/TrkB signaling (BDNF, p < 0.0001; Trk-B, p = 0.0005), altered lipid levels (CHOL, p < 0.0001; LDL, p < 0.0001; TG, p = 0.0006) and reduced hepatic ALAT (p = 0.0004) and GGT (p < 0.0001) activity, which may contribute to hepatic steatosis and obesity, as well as indicate impairment of specific metabolic pathways in the liver. Interestingly, endurance training did not alter hepatic BDNF and TrkB content, but improved ALAT (p = 0.0366) and ASAT (p = 0.0191) activities and increased hepatic IL-6 (p = 0.0422) levels in Bdnf +/- rats, suggesting enhanced liver regeneration in animals with BDNF allele loss.

Exercise Modifies the Brain Metabolic Response to Chronic Cocaine Exposure Inhibiting the Stria Terminalis.

It is well known that exercise promotes health and wellness, both mentally and physiologically. It has been shown to play a protective role in many diseases, including cardiovascular, neurological, and psychiatric diseases. The present study examined the effects of aerobic exercise on brain glucose metabolic activity in response to chronic cocaine exposure in female Lewis rats. Rats were divided into exercise and sedentary groups. Exercised rats underwent treadmill running for six weeks and were compared to the sedentary rats. Using positron emission tomography (PET) and [18F]-Fluorodeoxyglucose (FDG), metabolic changes in distinct brain regions were observed when comparing cocaine-exposed exercised rats to cocaine-exposed sedentary rats. This included activation of the secondary visual cortex and inhibition in the cerebellum, stria terminalis, thalamus, caudate putamen, and primary somatosensory cortex. The functional network of this brain circuit is involved in sensory processing, fear and stress responses, reward/addiction, and movement. These results show that chronic exercise can alter the brain metabolic response to cocaine treatment in regions associated with emotion, behavior, and the brain reward cascade. This supports previous findings of the potential for aerobic exercise to alter the brain's response to drugs of abuse, providing targets for future investigation. These results can provide insights into the fields of exercise neuroscience, psychiatry, and addiction research.

Reducing sugar intake through chronic swimming training: Exploring palatability changes and central vasopressin mechanisms

Excessive sugar intake has been associated with the onset of several non-communicable chronic diseases seen in humans. Physical activity could affect sweet taste perception which may affect sugar intake. Therefore, it was investigated the chronic effects of swimming training on sucrose intake/preference, reactivity to sucrose taste, self-care in neurobehavioral stress, and the possible involvement of the vasopressin type V1 receptor in sucrose solution intake. Male Wistar rats, of from different cohorts were used, subjected to a sedentary lifestyle (SED) or swimming training (TR - 1 h/day, 5×/week, for 8 weeks, with no added load). Weekly intake was verified in SED and TR rats after access to a sucrose solution 1×/week, 2 h/day, for eight weeks. Chronic effects of swimming and/or a sedentary lifestyle were carried out three days after the end of the physical exercise protocol. Swimming training reduced the intake of sucrose solution from the third week onwards in the two-bottle test measured once a week for 8 weeks. After the ending of the swimming protocol, sucrose intake was also reduced as per its preference. This reduced intake is probably correlated with the carbohydrate aspect of sucrose since saccharin intake was not affected. In addition, chronic swimming training was shown to reduce ingestive responses, increase neutral responses, without interfering with aversive, in the sucrose solution taste reactivity test. In addition, these results are not related to a depressive-like behavior, nor to neurobehavioral stress. Furthermore, treatment with vasopressin V1 receptor antagonist abolished the reduced sucrose intake in trained rats. The results suggest that swimming performed chronically is capable of reducing intake and preference for sucrose by decreasing the palatability of sucrose without causing depressive-type behavior or stress. In addition, the results also suggest that central V1 vasopressin receptors are part of the mechanisms activated to reduce sucrose intake in trained rats.

Atrial fibrosis and local right atrial inflammation are characteristic of strenuous, but not moderate exercise, and underlie increased AF inducibility in heavily trained rats

Abstract Introduction The U-shaped relationship between exercise load and atrial fibrillation (AF) risk, where moderate exercise is protective but strenuous training increases the risk of AF, is currently well accepted (1, 2). Clinical and experimental data suggest that atrial fibrosis and parasympathetic tone (PT) enhancement may underlie the excess risk of AF in endurance athletes (3). Delving into the atrial differences between moderate exercise and strenuous training may be important to understand the pathophysiology of exercise-induced AF. Purpose To compare the atrial structural, electrophysiological and molecular remodelling occurring after long-term moderate and strenuous exercise. Methods Male Wistar rats were randomly assigned to sedentary (SED), moderate (MOD, 35 cm/s, 45 minutes) or high intensity exercise (INT, 60 cm/s, 60 minutes) for 16 weeks. An electrocardiogram (ECG) and electrophysiological study (EPS) were performed before sacrifice. Left (LA) and right (RA) atrial samples were collected for fibrosis assessment and a mRNA array. Results After the exercise protocol, weight of SED rats was higher (486±77 g) compared with both the MOD (377±28 g) and INT groups (385±43 g). In the ECG (Figure 1), INT rats presented a prolonged P-wave compared with SED and MOD. Both trained groups presented with significant bradycardia compared with SED, along with enhanced PT (heart rate variability: low to high frequency ratio). The remaining ECG parameters were similar between groups. Consistent with an enhanced PT, the Wenckebach cycle length was similarly prolonged in both trained groups in the EPS. Conversely, the sinus node recovery time was prolonged in INT rats compared with SED and MOD. AF inducibility increased from SED to MOD to INT. Myocardial fibrosis was measured in atrial samples stained with Sirius red. In both the RA and LA, fibrosis was significantly higher in the INT group (6,3±0.8 %) compared with the SED (4,4±0.2 %) and MOD (4,3±0.5 %) groups. An mRNA array showed large differences between atria. 384 and 419 genes were deregulated between INT and MOD (nominal p&amp;lt;0.05) in the RA and LA, respectively. Only 19 genes were consistent between both atria. In pathway analyses, the inflammatory response pathway was enriched (upregulation) in the RA, but not in the LA, of INT rats compared with MOD (Figure 2). Conclusions In healthy rats, strenuous training promoted a differential, pathological remodelling involving atrial fibrosis and sinus node dysfunction, compared with moderate exercise. Local inflammation may play a role in strenuous exercise-induced fibrosis in the RA. PT enhancement was similar in both groups.Figure 1.Figure 2.

Voluntary wheel running prevents formation of membrane attack complexes and myelin degradation after peripheral nerve injury

Regular aerobic activity is associated with a reduced risk of chronic pain in humans and rodents. Our previous studies in rodents have shown that prior voluntary wheel running can normalize redox signaling at the site of peripheral nerve injury, attenuating subsequent neuropathic pain. However, the full extent of neuroprotection offered by voluntary wheel running after peripheral nerve injury is unknown. Here, we show that six weeks of voluntary wheel running prior to chronic constriction injury (CCI) reduced the terminal complement membrane attack complex (MAC) at the sciatic nerve injury site. This was associated with increased expression of the MAC inhibitor CD59. The levels of upstream complement components (C3) and their inhibitors (CD55, CR1 and CFH) were altered by CCI, but not increased by voluntary wheel running. Since MAC can degrade myelin, which in turn contributes to neuropathic pain, we evaluated myelin integrity at the sciatic nerve injury site. We found that the loss of myelinated fibers and decreased myelin protein which occurs in sedentary rats following CCI was not observed in rats with prior running. Substitution of prior voluntary wheel running with exogenous CD59 also attenuated mechanical allodynia and reduced MAC deposition at the nerve injury site, pointing to CD59 as a critical effector of the neuroprotective and antinociceptive actions of prior voluntary wheel running. This study links attenuation of neuropathic pain by prior voluntary wheel running with inhibition of MAC and preservation of myelin integrity at the sciatic nerve injury site.

Effects of Nandrolone Decanoate on Skeletal Muscle and Neuromuscular Junction of Sedentary and Exercised Rats.

Background and Objectives: Nandrolone decanoate (ND) is the most widely used among the anabolic androgenic steroids (AAS), synthetic substances derived from testosterone, to improve muscular and health gains associated with exercises. The AAS leads to physical performance enhancement and presents anti-aging properties, but its abuse is associated with several adverse effects. Supraphysiological doses of AAS with or without physical exercise can cause morphological and functional alterations in neuromuscular interactions. This study aims to investigate the effects of ND supraphysiological doses in neuromuscular interactions, focusing on the soleus muscle and its neuromuscular junctions (NMJs) in rats, associated or not with physical exercise. Materials and Methods: Forty male Sprague Dawley rats were divided into four groups: sedentary and exercised groups, with or without ND at the dose of 10 mg/kg/week. The animals were treated for eight weeks, with intramuscular injections, and the soleus muscle was collected for morphological analyses. Results: The supraphysiological doses of ND in the sedentary group caused muscle degeneration, evidenced by splitting fibers, clusters of small fibers, irregular myofibrils, altered sarcomeres, an increase in collagen deposition and in the number of type I muscle fibers (slow-twitch) and central nuclei, as well as a decrease in fibers with peripheral nuclei. On the other hand, in the ND exercise group, there was an increase in the NMJs diameter with scattering of its acetylcholine receptors, although no major morphological changes were found in the skeletal muscle. Thus, the alterations caused by ND in sedentary rats were partially reversed by physical exercise. Conclusions: The supraphysiological ND exposure in the sedentary rats promoted an increase in muscle oxidative pattern and adverse morphological alterations in skeletal muscle, resulting from damage or post-injury regeneration. In the ND-exercised rats, no major morphological changes were found. Thus, the physical exercise partially reversed the alterations caused by ND in sedentary rats.

Moderate- and High-Intensity Endurance Training Alleviate Diabetes-Induced Cardiac Dysfunction in Rats.

Exercise training is an encouraging approach to treat cardiac dysfunction in type 2 diabetes (T2DM), but the impact of its intensity is not understood. We aim to investigate whether and, if so, how moderate-intensity training (MIT) and high-intensity interval training (HIIT) alleviate adverse cardiac remodeling and dysfunction in rats with T2DM. Male rats received standard chow (n = 10) or Western diet (WD) to induce T2DM. Hereafter, WD rats were subjected to a 12-week sedentary lifestyle (n = 8), running MIT (n = 7) or HIIT (n = 7). Insulin resistance and glucose tolerance were assessed during the oral glucose tolerance test. Plasma advanced glycation end-products (AGEs) were evaluated. Echocardiography and hemodynamic measurements evaluated cardiac function. Underlying cardiac mechanisms were investigated by histology, western blot and colorimetry. We found that MIT and HIIT lowered insulin resistance and blood glucose levels compared to sedentary WD rats. MIT decreased harmful plasma AGE levels. In the heart, MIT and HIIT lowered end-diastolic pressure, left ventricular wall thickness and interstitial collagen deposition. Cardiac citrate synthase activity, mitochondrial oxidative capacity marker, raised after both exercise training modalities. We conclude that MIT and HIIT are effective in alleviating diastolic dysfunction and pathological cardiac remodeling in T2DM, by lowering fibrosis and optimizing mitochondrial capacity.

Selective Androgen Receptor Modulators Combined with Treadmill Exercise Have No Bone Benefit in Healthy Adult Rats.

The effects of combination treatments using the selective androgen receptor modulators (SARMs) ostarine (OST) or ligandrol (LIG) with treadmill exercise (TE) were studied in healthy adult rats. Fifteen-week-old male Wistar rats were divided into groups (n = 10/group). Experiment 1 consisted of (1) Control group: sedentary rats receiving vehicle; (2) OST: sedentary rats receiving OST; (3) TE: training rats receiving vehicle; (4) OST + TE: training rats receiving OST. Experiment 2 consisted of (1) LIG: sedentary group receiving LIG; (2) LIG + TE: training group receiving LIG. The TE regime was as follows: 25 m/min, 5° elevation, 40 min, five times/week, and the sedentary regime was 5 min, three times/week. OST and LIG were administered subcutaneously (0.4 mg/kg body weight/day, five times/week). After eight weeks, bone samples underwent microcomputed tomographical, biomechanical, histological, and ashing analyses. All the treatments had weak effects on the bone structure without affecting bone biomechanics. The OST + TE improved bone structure, while the LIG + TE had unfavorable effects. In serum, OST, OST + TE, and LIG + TE altered cholesterol and lipoprotein levels; TE did not change the serum parameters. The SARM treatments had no clear bone benefit, and the serum effects can be considered as side effects. TE represents a safe treatment. Because SARMs are increasingly applied in gyms along with physical activities, attention should be paid to possible side effects.

Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain

BackgroundExercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer's disease (AD). These beneficial effects may be partly mediated by blood-borne factors. Here we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability, and an in vivo rat model of AD to test whether such plasma impacts cognitive function, amyloid pathology, and neurogenesis. MethodsMouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-β and treated with plasma collected from human male donors 3 h after a single bout of high-intensity exercise. For in vivo studies, blood was collected from exercise-trained young male Wistar rats (high-intensity intervals 5 days/week for 6 weeks). Transgenic AD rats (McGill-R-Thy1-APP) were injected 5 times/fortnight for 6 weeks at 2 months or 5 months of age with either (a) plasma from the exercise-trained rats, (b) plasma from sedentary rats, or (c) saline. Cognitive function, amyloid plaque pathology, and neurogenesis were assessed. The plasma used for the treatment was analyzed for 23 cytokines. ResultsPlasma from exercised donors enhanced cell viability by 44.1% (p = 0.032) and reduced atrophy by 50.0% (p < 0.001) in amyloid-β-treated cells. In vivo exercised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippocampal neurogenesis by ∼3 fold, regardless of pathological stage, when compared to saline-treated rats. Concentrations of 7 cytokines were significantly reduced in exercised plasma compared to sedentary plasma. ConclusionOur proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote adult hippocampal neurogenesis in the AD rat brain. This effect may be partly due to reduced pro-inflammatory signaling molecules in exercised plasma.

Exercise training modifies the bone and endocrine response to graded reductions in energy availability in skeletally mature female rodents.

Reductions in energy availability leading to weight loss can induce loss of bone and impact important endocrine regulators of bone integrity. We sought to elucidate whether endurance exercise (EX) can mitigate bone loss observed in sedentary (SED) skeletally mature rodents subjected to graded energy deficits. Female virgin rats (n=84, 5-mo-old; 12/group) were randomized to baseline controls and either sedentary (SED) or exercise (EX) conditions, and within each exercise status to adlib-fed (ADLIB), or moderate (MOD) or severe (SEV) energy restriction diets for 12 weeks. Rats assigned to EX groups performed treadmill running to increase weekly energy expenditure by 10%. MOD-ER-SED, SEV-ER-SED, MOD-ER-EX and SEV-ER-EX were fed modified AIN93M diets with 20%, 40% 10%, and 30% less energy content, respectively, with 100% of all other nutrients provided. Energy availability (EA) was effectively reduced by ~14% and ~30% in the MOD-ER and SEV-ER groups, respectively. MOD-ER for 12 weeks resulted in few negative impacts on bone and, except for serum leptin in MOD-ER-SED rats, no significant changes in endocrine factors. By contrast, SEV-ER in SED rats resulted in significantly lower total body and femoral neck bone mass, and reduced serum estradiol, IGF-1 and leptin. EX rats experiencing the same reduction in energy availability as SEV-ER-SED exhibited higher total body mass, lean mass, total BMC, and higher serum IGF-1 at the end of 12 weeks. Bone mechanical properties at 3 bone sites (mid-femur, distal femur, femoral neck) were minimally impacted by ER but positively affected by EX. These findings indicate that combining increased EX energy expenditure with smaller reductions in energy intake to achieve a targeted reduction in EA provides some protection against loss of bone mass and lean mass in skeletally mature female rats, likely due to better preservation of circulating IGF-1, and that bone mechanical integrity is not significantly degraded with either moderate or severe reduced EA.

Arı Sütünün Tüketici Egzersize Bağlı Oksidatif Stres Üzerindeki Rolü

In this study, the effects of Royal Jelly (RJ) on oxidative stress caused by exhaustive swimming exercise in rat tissues were evaluated. Methods: Twenty four male Wistar albino rats were indiscriminately distributed into four experimental groups: Sedentary control (SC); SC with administration of RJ (100 mg kg-1) (SC + RJ); exhaustive swimming exercise (E); Exhaustive swimming exercise with administration of RJ (100 mg kg-1) (E + RJ). 100 mg kg-1 of RJ were dissolved in drinking water. Rats in the SC+RJ and E+RJ groups supplemented with RJ (100 mg kg-1) orally once a day for two weeks. Rats in groups E and E+RJ subjected to acute exhaustive swimming exercise on the 14th day of the study, then some biochemical parameters related to oxidative stress of all groups were measured. Results: The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN) and creatinine (CRE) levels significantly raised in the exercised rats compared with the sedentary rats (P &lt; 0.05). The decreased superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase (CAT) activities of muscular and hepatic tissues significantly increased and the high malondialdehyde (MDA) levels of muscular, hepatic and kidney tissues significantly reduced in exercised rats treated with RJ (P &lt; 0.05). Conclucion: Collectively, in this study, protective effects of RJ on tissues against oxidative damage after exhaustive exercise were observed.

588-P: Probing the Role of Muscle Glycogen Resynthesis on Postexercise AMPK Activation and Metabolic Protein Abundance Using a Novel Genetic Model

Acute exercise can alter the abundance of key metabolic proteins in skeletal muscle. These effects are influenced by postexercise (PEX) refeeding. Muscle glycogen resynthesis is a putative mediator of these refeeding effects. However, it is challenging to test this idea, because glycogen resynthesis is only one of many outcomes with refeeding. Therefore, we devised a novel genetic model to modify muscle expression of glycogen synthase 1 (GS1) using injection of rat skeletal muscle with adeno-associated viral (AAV) vectors for short hairpin RNA targeting GS1 (shRNA-GS1). Contralateral muscles were injected with scrambled shRNA (shRNA-Scr). Rats were sedentary (SED) or exercised (120min swim-exercise). Muscles were collected immediately postexercise (IPEX) and 9-hours PEX (9hPEX), along with time-matched SED controls. The 9hPEX and their SED-control rats were either refed (RF) or not-refed (NRF). Muscles were analyzed for glycogen and phosphorylation and abundance of key metabolic proteins. Muscles injected with shRNA-GS1 vs shRNA-Scr had lower GS1 abundance in all groups. Regardless of genotype, in IPEX vs SED rats: glycogen fell to similarly low values and phosphorylation of AMPK Thr172 (pAMPK) and its substrate ACC Ser79 (pACC) were comparably increased. Muscle glycogen was increased in all groups of 9h-RF rats, but it was lower for shRNA-GS1 vs shRNA-Scr from RF-9hPEX rats. In the NRF-9hPEX rats, pAMPK and pACC were greater for shRNA-GS1 vs shRNA-Scr muscles. Muscle pyruvate dehydrogenase kinase-4 abundance from 9hPEX rats (both NRF and RF) was greater for shRNA-GS1 vs shRNA-Scr. Hexokinase II (HKII) abundance was greater for 9hPEX vs SED in NRF rats regardless of genotype. In RF-9hPEX rats, HKII abundance was greater for shRNA-GS1 vs shRNA-Scr. These results support the idea that some PEX effects on metabolic protein abundance are influenced by muscle GS1 abundance and the extent of glycogen resynthesis Disclosure S.Kwak: None. A.Zheng: None. E.B.Arias: None. H.Wang: None. X.Pan: None. D.Duan: None. Y.Yue: None. G.D.Cartee: None. Funding National Institutes of Health (R01DK071771); University of Michigan

Lifelong exercise training promotes the remodelling of the immune system and prostate signalome in a rat model of prostate carcinogenesis

This work aimed to understand how lifelong exercise training promotes the remodelling of the immune system and prostate signalome in a rat model of PCa. Fifty-five male Wistar rats were divided into four groups: control sedentary, control exercised, induced PCa sedentary and induced PCa exercised. Exercised animals were trained in a treadmill for 53 weeks. Pca induction consisted on the sequential administration of flutamide, N-methyl-N-nitrosourea and testosterone propionate implants. Serum concentrations of C-reactive protein (CRP) and tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) were not different among groups. Peripheral levels of γδ T cells were higher in Pca exercised group than in the PCa sedentary group (p < 0.05). Exercise training also induced Oestrogen Receptor (ESR1) upregulation and Mitogen-activated Protein Kinase 13 (MAPK13) downregulation, changed the content of the phosphorylated (at Ser-104) form of this receptor (coded by the gene ESR1) and seemed to increase Erα phosphorylation and activity in exercised PCa rats when compared with sedentary PCa rats. Our data highlight the exercise-induced remodelling of peripheral lymphocyte subpopulations and lymphocyte infiltration in prostate tissue. Moreover, exercise training promotes the remodelling prostate signalome in this rat model of prostate carcinogenesis.

EFFECTS OF SWIMMING TRAINING IN OBESITY INSTALLATION IN ADULTS OFFSPRING BORN WITHIN A SMALL LITTER

The excessive supply of energy during pregnancy and breastfeeding period, favors the highaccumulation of white adipose tissue (WAT) throughout life, commonly associated withinsulin resistance (IR), dyslipidemia and cardiovascular disease in adulthood. Chronic aerobicexercises reduce accumulation of WAT, preventing the development of metabolic diseases.On the 2 nd postnatal day, litter size was set to: normal (NL) with 9 pups per mother and small(SL) with 3 pups per mother, was used just male rats. After weaning (21 days), NL and SLrats, were divided into sedentary (Sed) and exercised (Exe), forming 4 experimentalsubgroups; NL Sed , NL Exe , SL Sed and SL Exe . From 22–90 days of life exercised groups performedswimming training 3 times for week during 30 minutes. Litter handling influenced bodyweight, retroperitoneal and mesenteric-WAT (p&amp;lt;0.0001) in adulthood. SL Sed animals showedan increase in these parameters when compared to NL Sed and NL Exe animals (P&amp;lt;0.0001).Swimming training reduced body weight and WAT deposits in NL and SL groups(P&amp;lt;0.0001). SL Sed and SL Exe animals showed elevated glucose values at 2h post-glucose loadwhen compared to NL animals. Kitt was also altered by litter reduction (P&amp;lt;0.0001), with SL Sedanimals had higher Kitt values compared to NL Sed and NL Exe rats. This response wasnormalized in SL Exe group.We conclude that lactational hypernutrition causes obesityassociated with disruption of glucose homeostasis and swimming training normalizes insulinsensitivity but is insufficient to restore glucose homeostasis during glucose tolerance test.

Exercise augments small conductance Ca2+ -activated potassium channel (SK) function in the paraventricular nucleus (PVN) of Sprague Dawley rats to reduce sympathetic outflow

Elevated sympathetic outflow is a key feature of cardiovascular disease (CVD) that worsens disease progression. Our lab has shown that SK channels expressed in the PVN play a crucial role in regulating neuronal activity and sympathetic outflow, and that SK channels become dysfunctional in rats fed a high salt diet. Exercise has been shown to be an effective treatment for reducing sympathoexcitation in CVD including hypertension and heart failure, but the underlying mechanisms are not fully understood. We hypothesized that aerobic exercise would upregulate SK channel function in the PVN to reduce sympathetic nerve activity (SNA). To test this, 5–6 week old Sprague Dawley rats were randomly divided into sedentary (SED) and exercise (EXT) two groups and fed a 0.4% NaCl normal salt diet. Following acclimation, EXT groups ran on a motorized treadmill 5 days/week for 8-10 weeks. Conscious blood pressure was measured weekly via tail plethysmography. After 8-10 weeks, animals were anesthetized and underwent in vivo surgery to record the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) following PVN microinjection of the SK channel blocker, apamin (0.25mM, 60nL/side). The data showed that the RSNA response to PVN apamin was significantly enhanced in EXT rats compared with SED rats (320.8 ± 174.6 % baseline, n=9 vs 184.8 ± 143.1 % baseline, n=9; p = 0.02). The corresponding ABP response to apamin was not significantly different in EXT rats compared with SED rats (20.40 ± 9.98 mmHg, n=9 vs 25.27 ± 9.97 mmHg, n=8; p = 0.1658). Our data indicates exercise enhances PVN SK channel function to reduce sympathetic outflow. This improvement of SK channel function may be one mechanism by which exercise reduces SNA in CVD including hypertension and heart failure. Support: 1R15HL145655 (Chen); 1R15 HL150703 (Shan); MTU Health Research Institute. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sympathetic pressor responses to glutamate nanoinjections in the rostral ventrolateral medulla are influenced by ovarian hormones in active but not sedentary female rats

Cardiovascular disease (CVD) is the leading cause of death worldwide. One of the leading risk factors for CVD is hypertension. The incidence of hypertension in females increases drastically after the onset of menopause, suggesting female reproductive hormones have cardioprotective effects. However, the interaction between female reproductive hormones and blood pressure-lowering effects of regular physical activity are poorly understood. Blood pressure is controlled by a region of the brainstem known as the rostral ventrolateral medulla (RVLM). Previously, we reported that female rats had lower resting blood pressure than male rats, but had higher sympathoexcitatory responses to direct activation of the RVLM, as did sedentary animals from both sexes. Therefore, the purpose of our study was to examine the interaction between ovarian hormones and sedentary and active conditions. We hypothesized that during low or high hormone stages, sedentary female rats would have higher blood pressure responses to activation of the RVLM compared to the physically active female rats. In addition, we hypothesized that ovariectomy (OVX) would reduce the ability of exercise to blunt pressor responses to RVLM activation. OVX or sham surgeries were performed at four weeks of age and groups were split into active (running wheels) or sedentary conditions (no running wheels) for 12 weeks. At 16 weeks of age, vaginal lavages were collected under Isoflurane anesthesia to categorize stages of the estrous cycle and all rats received glutamate nanoinjections (1, 10, &amp; 100 mM; 30 nl ea.) into the RVLM, under Inactin anesthesia. Sedentary versus active conditions promoted significantly greater pressor responses to nanoinjections of glutamate (100 mM) in the RVLM in both the high hormone (proestrus/estrus; 25±2 vs 14±3 mmHg, p&lt;0.001) and low hormone (diestrus/metestrus; 21±2 vs 14±2 mmHg, p=0.007) groups. In OVX rats, the beneficial effects of exercise appeared to be lost as pressor responses to 100 mM of glutamate were similar in sedentary versus active rats (20±2 vs 25±6 mmHg, resp., p&gt;0.05). Our results indicate that the absence of ovarian hormones offset the decreased pressor responses originating from the RVLM in active but not sedentary animals and could help explain the increased risk for CVD in females after menopause. They also demonstrate the increased risks of CVD and hypertension associated with a sedentary lifestyle as a result of this greater sensitivity to sympathoexcitation. 1R01-HL161233 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

BDNF-related mechanisms of neuroplasticity in the rostral ventrolateral medulla of sedentary versus active rats

Overactivity of the sympathetic nervous system is implicated in cardiovascular disease (CVD), the leading cause of death. Sympathetic nerve activity is regulated by a region in the brainstem, the rostral ventrolateral medulla (RVLM). The RVLM contains sympathoexcitatory neurons, which when overactive, likely contribute to hypertension, a leading risk factor for CVD. RVLM neurons undergo structural and functional neuroplasticity. Our laboratory reported that sedentary vs active conditions promote increased dendritic branching in rostral regions of the RVLM. Increased dendritic branching is consistent with previous observations of greater sympathoexcitation after activation of the RVLM in sedentary vs active rats. Regulation of dendritic branching is mediated by brain-derived neurotrophic factor (BDNF). Interestingly, the mature form (mBDNF) but not its precursor (proBDNF) is significantly elevated in rostral regions of the RVLM in sedentary rats. Since conversion of proBDNF to mBDNF is facilitated by tissue plasminogen activator (tPA), the purpose of this study was to determine whether tPA expression in the RVLM is different under sedentary vs active conditions. We hypothesized that tPA levels are higher in rostral regions of the RVLM of sedentary vs active animals. Four-week-old, male Sprague-Dawley rats were divided into two groups: Active (running wheels) or Sedentary (no running wheel) for 12 weeks (n=4 ea.). Rats were sacrificed for fresh tissue removal under deep anesthesia, and brainstems were cryosectioned serially (80 μm). Bilateral tissue punches of the RVLM were retrieved and rostrocaudal boundaries were verified by cresyl violet staining of post-punched sections. Bilateral punches were pooled for gel electrophoresis based on rostrocaudal location. Expression levels of tPA and GAPDH (loading control) were detected using fluorescent immunoblotting and acquisition on a Typhoon Laser-scanner. Band densities were quantified using ImageQuant software. Sedentary conditions resulted in significant increases in tPA/GAPDH in the most rostral RVLM region compared to the two caudal regions (p=0.0006, for both; two way ANOVA). In contrast, active conditions did not result in increases of tPA/GAPDH in rostral vs caudal regions of the RVLM (p&gt;0.05, across all levels); appearing lower in the most rostral region compared to sedentary rats (p=0.085). Interestingly, tPA/GAPDH was significantly lower in the most caudal region of the RVLM in sedentary vs active rats (p=0.017). Our data suggests that sedentary conditions may drive increased tPA and possibly greater conversion of proBDNF to mBDNF in the rostral RVLM. However, higher tPA expression may also contribute to similar branching following active conditions in the caudal RVLM compared to sedentary rats. Thus, additional studies are necessary to clarify the role of tPA in mechanisms of neuroplasticity in RVLM neurons involved in blood pressure regulation in sedentary vs active animals. 1R01-HL161233 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.