Chronic enhancement of neuromuscular activity increases acetylcholinesterase gene expression in skeletal muscle

We determined levels of mRNA encoding acetylcholinesterase (AChE) in muscles of rats subjected to chronic enhancement of neuromuscular activation. After 8 wk of voluntary wheel running, extensor digitorum longus (EDL) muscles displayed a 72% increase in total AChE activity as a result of a selective threefold increase in the G4 content. Soleus muscles, on the other hand, exhibited a 30% decrease in A12 while displaying a small (33%) increase in total AChE activity. These enzymatic adaptations were paralleled by increases in the levels of AChE mRNAs in both EDL (32%; P < 0.03) and soleus (42%; P < 0.02) muscles. In addition, compensatory hypertrophy of the plantaris muscle increased total AChE activity by 75%. This change was reflected by an elevation in all AChE molecular forms with A12 (89%) and A8 (179%) showing the most prominent increases. Similar to exercise-trained muscles, hypertrophied plantaris muscles displayed an increase in AChE transcripts (25%; P < 0.04). These results indicate that increases in neuromuscular activity modulate expression of the AChE gene in vivo and suggest the involvement of pretranslational regulatory mechanisms in the adaptive response of AChE to enhanced neuromuscular activation.

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Abstract 12231: PECAM1 is Essential for Flow-mediated Gab1 Tyrosine Phosphorylation and Signaling in vitro and in vivo

Circulation ◽

10.1161/circ.132.suppl_3.12231 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Suowen Xu ◽

Marina Koroleva ◽

Keigi Fujiwara ◽

Zheng Gen Jin

Keyword(s):

Tyrosine Phosphorylation ◽

Wheel Running ◽

Tyrosine Phosphatase ◽

Common Mechanism ◽

Membrane Localization ◽

No Production ◽

Voluntary Wheel Running ◽

Voluntary Wheel

Introduction: Impaired activation of endothelial nitric oxide (NO) synthase (eNOS) and ensued NO production is a common mechanism of various cardiovascular pathologies, including hypertension and atherosclerosis. Specific signaling cascades, generated by vascular endothelial cells (ECs) in response to laminar flow, modulate EC structure and functions, NO production in particular. We have previously shown that flow-stimulated Gab1 (Grb2-associated binder-1) tyrosine phosphorylation mediates eNOS activation. However, the upstream mechanism that regulates Gab1 tyrosine phosphorylation remains unclear. Hypothesis: We hypothesized that platelet endothelial cell adhesion molecule-1 (PECAM1), a key molecule in an endothelial mechanosensing complex, specifically mediates Gab1 tyrosine phosphorylation and its downstream Akt and eNOS activation in ECs upon flow rather than hepatocyte growth factor (HGF) stimulation. Methods: Western blot, en face staining and voluntary wheel running. Results: Small interfering RNA (siRNA) targeting PECAM1 abolished flow- but not HGF-induced Gab1 tyrosine phosphorylation and Akt, eNOS activation as well as Gab1 membrane translocation. Protein-tyrosine phosphatase SHP2, which has been shown to interact with Gab1, was involved in a flow signaling pathway as well as HGF-induced signaling, as SHP2 siRNA diminished the flow- and HGF-induced Gab1 tyrosine phosphorylation, membrane localization and downstream signaling. Pharmacological inhibition of PI3K by LY294002 decreased flow, but not HGF-mediated Gab1 phosphorylation and membrane localization as well as eNOS activation. Finally, we observed that flow-mediated Gab1 and eNOS phosphorylation in vivo induced by voluntary wheel running was reduced in PECAM1 knockout mice. Conclusions: These results demonstrate a specific role of PECAM1 in flow-mediated Gab1 tyrosine phosphorylation and eNOS signaling in ECs

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Effects of a high-fat diet and voluntary wheel running on gluconeogenesis and lipolysis in rats

Journal of Applied Physiology ◽

10.1152/jappl.1999.86.4.1374 ◽

1999 ◽

Vol 86 (4) ◽

pp. 1374-1380 ◽

Cited By ~ 26

Author(s):

Deborah A. Podolin ◽

Yuren Wei ◽

Michael J. Pagliassotti

Keyword(s):

High Fat Diet ◽

Corn Oil ◽

Wheel Running ◽

Whole Body ◽

Free Access ◽

Fat Pad ◽

High Fat ◽

Voluntary Wheel Running ◽

Voluntary Wheel

The purpose of the present study was to determine the effects of diet composition and exercise on glycerol and glucose appearance rate (Ra) and on nonglycerol gluconeogenesis (Gneo) in vivo. Male Wistar rats were fed a high-starch diet (St, 68% of energy as cornstarch, 12% corn oil) for a 2-wk baseline period and then were randomly assigned to one of four experimental groups: St ( n = 7), high-fat (HF; 35% cornstarch, 45% corn oil; n = 8), St with free access to exercise wheels (StEx; n = 7), and HF with free access to exercise wheels (HFEx; n = 7). After 8 wk, glucose Rawhen using [3-3H]glucose, glycerol Rawhen using [2H5]glycerol (estimate of whole body lipolysis), and [3-13C]alanine incorporation into glucose (estimate of alanine Gneo) were determined. Body weight and fat pad mass were significantly ( P < 0.05) decreased in exercise vs. sedentary animals only. The average amount of exercise was not significantly different between StEx (3,212 ± 659 m/day) and HFEx (3,581 ± 765 m/day). The ratio of glucose to alanine enrichment and absolute glycerol Ra(μmol/min) were higher ( P < 0.05) in HF and HFEx compared with St and StEx rats. In separate experiments, the ratio of3H in C-2 to C-6 of glucose from3H2O (estimate of Gneo from pyruvate) was also higher ( P < 0.05) in HF ( n = 5) and HFEx ( n = 5), compared with St ( n = 5) and StEx ( n = 5) rats. Voluntary wheel running did not significantly increase estimated alanine or pyruvate Gneo or absolute glycerol Ra. Voluntary wheel running increased ( P< 0.05) glycerol Rawhen normalized to fat pad mass. These data suggest that a high-fat diet can increase in vivo Gneo from precursors that pass through pyruvate. They also suggest that changes in the absolute rate of glycerol Ramay contribute to the high-fat diet-induced increase in Gneo.

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Effect of Voluntary Wheel Running on Striatal Dopamine Level and Neurocognitive Behaviors after Molar Loss in Rats

Behavioural Neurology ◽

10.1155/2017/6137071 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Linlin Zhang ◽

Yi Feng ◽

Wenliang Ji ◽

Jianzhang Liu ◽

Kun Liu

Keyword(s):

Physical Exercise ◽

Wheel Running ◽

Striatal Dopamine ◽

Control Group ◽

Dopamine Level ◽

Sprague Dawley ◽

Voluntary Wheel Running ◽

Cognition And Emotion ◽

Voluntary Wheel

The aim of the present study is to evaluate the effect of voluntary wheel running on striatal dopamine level and behavior of cognition and emotion in molar loss rats. Twenty-four Sprague-Dawley rats were enrolled in this study and randomly divided into following 4 groups: control group (C group), molar loss group (ML group), 1-week physical exercise before molar loss group (1W-ML group), and 4-week physical exercise before molar loss group (4W-ML group). The rats both in 4W-ML and 1W-ML groups were placed in the voluntary running wheel in order to exercise for 4 weeks and 1 week, respectively. Then, the rats in 4W-ML, 1W-M, and ML groups received bilateral molar loss operation. After 10 days, striatal dopamine level was detected by in vivo microdialysis coupled with high-performance liquid chromatography (HPLC) and electrochemical detection. All the rats received behavior test after microdialysis detection. The behavior tests including passive avoidance test were used to assess cognition and elevated plus maze test for emotion. The results indicated that voluntary wheel running promoted striatal dopamine level in rats of molar loss. Behavioral data indicated that voluntary wheel running promoted cognition and emotion recovery after molar loss. Therefore, we concluded physical exercise significantly improved the neurocognitive behaviors and increased the striatal dopamine level after molar loss in rats.

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Comparison of changes in electrical activity, in isolated and in vivo hearts, induced by voluntary exercise in female rats

10.1101/2020.11.16.385021 ◽

2020 ◽

Author(s):

Rachel Stones ◽

Mark Drinkhill ◽

Ed White

Keyword(s):

Exercise Training ◽

Electrical Activity ◽

Wheel Running ◽

Left Ventricular ◽

Voluntary Exercise ◽

Female Rats ◽

Heart Weight ◽

Voluntary Wheel Running ◽

Voluntary Wheel

AbstractRegular mild exercise is recommended to the general population as beneficial to health. Regular exercise typically leads to structural and electrical remodelling of the heart but in human studies it is difficult to relate the extrinsic and intrinsic influences on intact hearts to changes seen at the single cell level. In this study we wished to test whether changes in electrical activity in intact hearts, in response to voluntary wheel running exercise training, were consistent with our previous observations in single cardiac myocytes and whether these changes resulted in altered susceptibility to arrhythmic stimuli.Female rats performed 5 weeks of voluntary wheel running. Implanted telemetry transmitters were used to measure electrocardiograms (ECGs) and determine heart rate variability (HRV) in conscious, unrestrained, trained (TRN) and sedentary (SED) animals. In isolated hearts, left ventricular epicardial monophasic action potentials (MAPs) were recorded and the responses to potentially arrhythmic interventions were assessed.Exercise training caused cardiac hypertrophy, as indexed by a significantly greater heart weight to body weight ratio. Consistent with previous measurements of action potential duration in single myocytes, MAPs were significantly longer at 50%, 75% and 90% repolarization. Arrhythmic susceptibility was not different between SED and TRN hearts. Trained animals displayed significantly altered HRV by week 5, in a manner consistent with reduced sympathetic tone, however resting ECG parameters, including those most associated with repolarisation duration, were unaltered. We conclude that intrinsic changes to cellular cardiac electrophysiology, induced by mild voluntary exercise, are not attenuated by the electronic loading that occurs in intact hearts. However, in vivo, extrinsic neuro-hormonal control of the heart may minimize the effects of intrinsic alterations in electrical activity.

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Voluntary wheel running increases satellite cell abundance and improves recovery from disuse in gastrocnemius muscles from mice

Journal of Applied Physiology ◽

10.1152/japplphysiol.00451.2017 ◽

2018 ◽

Vol 124 (6) ◽

pp. 1616-1628 ◽

Cited By ~ 11

Author(s):

Matthew J. Brooks ◽

Ameena Hajira ◽

Junaith S. Mohamed ◽

Stephen E. Alway

Keyword(s):

Satellite Cell ◽

Cell Activation ◽

Wheel Running ◽

Cell Activity ◽

Type I ◽

Cross Sectional ◽

Voluntary Wheel Running ◽

Satellite Cell Activity ◽

Voluntary Wheel

Reloading of atrophied muscles after hindlimb suspension unloading (HSU) can induce injury and prolong recovery. Low-impact exercise, such as voluntary wheel running, has been identified as a nondamaging rehabilitation therapy in rodents, but its effects on muscle function, morphology, and satellite cell activity after HSU are unclear. This study tested the hypothesis that low-impact wheel running would increase satellite cell proliferation and improve recovery of muscle structure and function after HSU in mice. Young adult male and female C57BL/6 mice ( n = 6/group) were randomly placed into five groups. These included HSU without recovery (HSU), normal ambulatory recovery for 14 days after HSU (HSU+NoWR), and voluntary wheel running recovery for 14 days after HSU (HSU+WR). Two control groups were used: nonsuspended mouse cage controls (Control) and voluntary wheel running controls (ControlWR). Satellite cell activation was evaluated by providing mice 5-bromo-2′-deoxyuridine (BrdU) in their drinking water. As expected, HSU significantly reduced in vivo maximal force, decreased in vivo fatigability, and decreased type I and IIa myosin heavy chain (MHC) abundance in plantarflexor muscles. HSU+WR mice significantly improved plantarflexor fatigue resistance, increased type I and IIa MHC abundance, increased fiber cross-sectional area, and increased the percentage of type I and IIA muscle fibers in the gastrocnemius muscle. HSU+WR mice also had a significantly greater percentage of BrdU-positive and Pax 7-positive nuclei inside muscle fibers and a greater MyoD-to-Pax 7 protein ratio compared with HSU+NoWR mice. The mechanotransduction protein Yes-associated protein (YAP) was elevated with reloading after HSU, but HSU+WR mice had lower levels of the inactive phosphorylated YAPserine127, which may have contributed to increased satellite cell activation with reloading after HSU. These results indicate that voluntary wheel running increased YAP signaling and satellite cell activity after HSU and this was associated with improved recovery. NEW & NOTEWORTHY Although satellite cell involvement in muscle remodeling has been challenged, the data in this study suggest that voluntary wheel running increased satellite cell activity and suppressed Yes-associated protein (YAP) protein relative to no wheel running and this was associated with improved muscle recovery of force, fatigue resistance, expression of type I myosin heavy chain, and greater fiber cross-sectional area after disuse.

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Activation pattern of ACE2/Ang-(1–7) and ACE/Ang II pathway in course of heart failure assessed by multiparametric MRI in vivo in Tgαq*44 mice

Journal of Applied Physiology ◽

10.1152/japplphysiol.00571.2017 ◽

2018 ◽

Vol 124 (1) ◽

pp. 52-65 ◽

Cited By ~ 7

Author(s):

Urszula Tyrankiewicz ◽

Mariola Olkowicz ◽

Tomasz Skórka ◽

Magdalena Jablonska ◽

Anna Orzylowska ◽

...

Keyword(s):

Heart Failure ◽

Wheel Running ◽

Late Onset ◽

Early Stage ◽

Multiparametric Mri ◽

Ang Ii ◽

Voluntary Wheel Running ◽

End Stage ◽

Voluntary Wheel

Here, we analyzed systemic (plasma) and local (heart/aorta) changes in ACE/ACE-2 balance in Tgαq*44 mice in course of heart failure (HF). Tgαq*44 mice with cardiomyocyte-specific Gαq overexpression and late onset of HF were analyzed at different age for angiotensin pattern in plasma, heart, and aorta using liquid chromatography/mass spectrometry, for progression of HF by in vivo magnetic resonance imaging under isoflurane anesthesia, and for physical activity by voluntary wheel running. Six-month-old Tgαq*44 mice displayed decreased ventricle radial strains and impaired left atrial function. At 8–10 mo, Tgαq*44 mice showed impaired systolic performance and reduced voluntary wheel running but exhibited preserved inotropic reserve. At 12 mo, Tgαq*44 mice demonstrated a severe impairment of basal cardiac performance and modestly compromised inotropic reserve with reduced voluntary wheel running. Angiotensin analysis in plasma revealed an increase in concentration of angiotensin-(1–7) in 6- to 10-mo-old Tgαq*44 mice. However, in 12- to 14-mo-old Tgαq*44 mice, increased angiotensin II was noted with a concomitant increase in Ang III, Ang IV, angiotensin A, and angiotensin-(1–10). The pattern of changes in the heart and aorta was also compatible with activation of ACE2, followed by activation of the ACE pathway. In conclusion, mice with cardiomyocyte Gαq protein overexpression develop HF that is associated with activation of the systemic and the local ACE/Ang II pathway. However, it is counterbalanced by a prominent ACE2/Ang-(1–7) activation, possibly allowing to delay decompensation. NEW & NOTEWORTHY Changes in ACE/ACE-2 balance were analyzed based on measurements of a panel of nine angiotensins in plasma, heart, and aorta of Tgαq*44 mice in relation to progression of heart failure (HF) characterized by multiparametric MRI and exercise performance. The early stage of HF was associated with upregulation of the ACE2/angiotensin-(1–7) pathway, whereas the end-stage HF was associated with downregulation of ACE2/angiotensin-(1–7) and upregulation of the ACE/Ang II pathway. ACE/ACE-2 balance seems to determine the decompensation of HF in this model.

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Hippocampal Morphology in a Rat Model of Depression: The Effects of Physical Activity

The Open Neuroimaging Journal ◽

10.2174/1874440001509010001 ◽

2015 ◽

Vol 9 (1) ◽

pp. 1-6 ◽

Cited By ~ 11

Author(s):

Adam Sierakowiak ◽

Anna Mattsson ◽

Marta Gómez-Galán ◽

Teresa Feminía ◽

Lisette Graae ◽

...

Keyword(s):

Physical Activity ◽

Genetic Model ◽

Wheel Running ◽

Ex Vivo ◽

Hippocampal Volume ◽

Antidepressant Effect ◽

Spine Density ◽

Voluntary Wheel Running ◽

Voluntary Wheel

Accumulating in vivo and ex vivo evidences show that humans suffering from depression have decreased hippocampal volume and altered spine density. Moreover, physical activity has an antidepressant effect in humans and in animal models, but to what extent physical activity can affect hippocampal volume and spine numbers in a model for depression is not known. In this study we analyzed whether physical activity affects hippocampal volume and spine density by analyzing a rodent genetic model of depression, Flinders Sensitive Line Rats (FSL), with Magnetic Resonance Imaging (MRI) and ex vivo Golgi staining. We found that physical activity in the form of voluntary wheel running during 5 weeks increased hippocampal volume. Moreover, runners also had larger numbers of thin spines in the dentate gyrus. Our findings support that voluntary wheel running, which is antidepressive in FSL rats, is associated with increased hippocampal volume and spine numbers.

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Combined overexpression of SIRT1 and knockout of GCN5 in adult skeletal muscle does not affect glucose homeostasis or exercise performance in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00370.2019 ◽

2020 ◽

Vol 318 (2) ◽

pp. E145-E151 ◽

Cited By ~ 3

Author(s):

Kristoffer Svensson ◽

Shahriar Tahvilian ◽

Vitor F. Martins ◽

Jessica R. Dent ◽

Adrianna Lemanek ◽

...

Keyword(s):

Skeletal Muscle ◽

Glucose Homeostasis ◽

Mitochondrial Biogenesis ◽

Exercise Performance ◽

Wheel Running ◽

Contractile Function ◽

Muscle Contractile ◽

Combined Overexpression ◽

Voluntary Wheel

Sirtuin 1 (SIRT1) and general control of amino acid synthesis 5 (GCN5) regulate mitochondrial biogenesis via opposing modulation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) acetylation status and activity. However, the combined contribution of SIRT1 and GCN5 to skeletal muscle metabolism and endurance performance in vivo is unknown. In this study, we investigated the impact of combined skeletal muscle-specific overexpression of SIRT1 and deletion of GCN5 on glucose homeostasis, skeletal muscle mitochondrial biogenesis and function, and metabolic adaptation to endurance exercise training in mice. We generated mice with combined and tamoxifen-inducible skeletal muscle-specific overexpression of SIRT1 and knockout of GCN5 (dTG) and floxed [wild type (WT)] littermates using a Cre-LoxP approach. All mice were treated with tamoxifen at 5–6 wk of age, and 4–7 wk later glucose homeostasis, skeletal muscle contractile function, mitochondrial function, and the effects of 14 days of voluntary wheel running on expression of metabolic proteins and exercise capacity were assessed. There was no difference in oral glucose tolerance, skeletal muscle contractile function, mitochondrial abundance, or maximal respiratory capacity between dTG and WT mice. Additionally, there were no genotype differences in exercise performance and markers of mitochondrial biogenesis after 14 days of voluntary wheel running. These results demonstrate that combined overexpression of SIRT1 and loss of GCN5 in vivo does not promote metabolic remodeling in skeletal muscle of sedentary or exercise-trained mice.

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The amount of acetylcholinesterase on the parasite surface reflects the differential sensitivity of schistosome species to metrifonate

Parasitology ◽

10.1017/s0031182000068244 ◽

1994 ◽

Vol 108 (2) ◽

pp. 153-160 ◽

Cited By ~ 29

Author(s):

M. Camacho ◽

R. Tarrab-Hazdai ◽

B. Espinoza ◽

R. Arnon ◽

A. Agnew

Keyword(s):

Life Cycle ◽

Ache Activity ◽

Schistosoma Haematobium ◽

Adult Stage ◽

Molecular Form ◽

Differential Sensitivity ◽

Molecular Forms ◽

Ache Inhibitors ◽

Schistosoma Bovis

SUMMARYAcetylcholinesterase (AChE) is present in all stages of the life-cycle of schistosomes and is located in muscle and on the surface of the parasite. Metrifonate is a drug that inhibits AChE. We compared the AChEs from three schistosome species (Schistosoma mansoni, Schistosoma haematobium and Schistosoma bovis) that have different susceptibilities to metrifonate in vivo. Sensitivities to AChE inhibitors were similar. The subunits of AChE were 110 kDa and 76 kDa and the dominant molecular form of AChE was a G2 form in all three species. This was the major form on the tegument while additional molecular forms were associated with the internal tissues. Differences in relative amounts of AChE activity between these species were found in the adults but not in the schistosomula. At the adult stage the major difference between species lay in the relative amounts of AChE activity in their teguments. S. haematobium teguments carried 20 times and S. bovis 6·9 times the activity present on S. mansoni teguments. These quantitative differences associate with the relative sensitivities of these species to metrifonate.

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