ABSTRACT
OBJECTIVE: This study aims to examine the effect of sepsis on the dynamics of skeletal muscle partial oxygen pressure during muscle contractions as well as the effect of reactive oxygen species (ROS) scavenger (ascorbic acid, Asc). METHODS: Twenty-seven male Sprague-Dawley rats (2-3 months old) were randomly assigned to three groups; sham, cecal ligation and puncture (CLP), or CLP plus ascorbic acid treatment group (CLP + Asc). Electrical stimuli-induced muscle contractions and partial oxygen pressure measurements were performed at 3 h after CLP. The interstitial oxygen pressure (PO2 is) in the spinotrapezius muscle was measured by the phosphorescence quenching method. RESULTS: The PO2 is at rest was not different between the three groups. The PO2 is decreased from rest to contraction in all groups. Compared to the sham, the time to decrease PO2 is was significantly faster in CLP but not in CLP + Asc (p < .05). Compared to the sham, the PO2 is during muscle contractions was significantly lower in both CLP and CLP + Asc (p < .05, respectively). CONCLUSIONS: Our results suggest that CLP-induced sepsis accelerated the decay of PO2 is at the onset of muscle contractions and maintained a low level of PO2 is during muscle contractions.
Subject(s)
Reactive Oxygen Species , Sepsis , Animals , Male , Rats , Ascorbic Acid/pharmacology , Muscle, Skeletal/physiology , Oxygen , Rats, Sprague-Dawley , Reactive Oxygen Species/pharmacologyABSTRACT
OBJECTIVE: This study aimed to clarify the effect of Type I diabetes (DIA) on transcapillary PO2 gradients, which are oxygen-driving factors between the blood and the interstitium, in the contracting muscle of rats. METHODS: Wistar male rats were divided into the diabetic (streptozocin i.p.) and sham groups. Microvascular and interstitial PO2 were measured in the extensor digitorum longus muscle during electrical stimulation-induced muscle contraction, using the phosphorescence quenching method. Transcapillary PO2 gradient, ΔPO2, was calculated as microvascular minus interstitial PO2. RESULTS: Resting microvascular PO2 was higher in the diabetic group than in the sham group (6.3 ± 1.7 vs. 4.7 ± 0.9 mmHg, p < 0.05) and remained for 180 s. Interstitial PO2 from rest to muscle contraction did not differ between the groups. The ΔPO2 was higher in the diabetic group than in the sham group at rest and during muscle contraction (4.03 ± 1.42 vs. 2.46 ± 0.90 mmHg at rest; 3.67 ± 1.51 vs. 2.22 ± 0.65 mmHg during muscle contraction, p < 0.05). Marked muscle atrophy was observed in the diabetic group. CONCLUSION: DIA increased microvascular and transcapillary PO2 gradients in the skeletal muscle. The enhanced PO2 gradients were maintained from rest to muscle contraction in diabetic muscle.
Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1 , Muscle Contraction , Muscle, Skeletal , Oxygen , Rats, Wistar , Animals , Male , Rats , Muscle, Skeletal/metabolism , Muscle, Skeletal/physiopathology , Muscle, Skeletal/blood supply , Oxygen/metabolism , Diabetes Mellitus, Experimental/physiopathology , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 1/metabolism , Capillaries/metabolism , Capillaries/physiopathology , Capillaries/pathology , Microcirculation , Muscular Atrophy/metabolism , Muscular Atrophy/physiopathology , Muscular Atrophy/pathologyABSTRACT
PURPOSE: Chronic physical stress in female athletes can reduce mental health and athletic performance. Therefore, a chronic physical stress assessment method is required. METHODS: This study examined whether hair cortisol concentration (HCC) predicted chronic physical stress changes in female university football players. We took measurements in August and December, just before the Japan college national tournament. RESULTS: Self-reported training load was significantly positively correlated with HCC. Self-reported training load had no significant relationship with fatigue as measured by the Profile of Mood States 2nd Edition or with the stressors from the Stressor Scale for College Students. HCC was negatively correlated with reaction time in the spatial Stroop task, although the repeated correlation analysis showed no significant relationship. CONCLUSION: These results suggest that the chronic physical stress experienced by female footballers cannot be predicted by psychological indicators; however, they can be predicted by HCC, which could be used to prevent overtraining in these athletes.
ABSTRACT
A 28-year-old female patient with no particular medical history had a sore throat seven days before admission. Subsequently, she developed malaise, right abdominal pain, and a fever of 38°C and visited our hospital. A blood test revealed a mild inflammatory response and elevated liver enzymes, and she was admitted to the hospital for detailed examination and acute liver injury treatment. Various viral tests and autoantibody measurements revealed elevated Epstein-Barr virus (EBV) immunoglobulin M and negative EB nuclear antigen antibodies. Therefore, she was diagnosed with primary infectious mononucleosis-associated EB viral hepatitis. Abdominal computed tomography upon admission revealed swollen lymph nodes around the stomach;thus, esophagogastroduodenoscopy (EGD) was performed. A histopathological examination revealed severe lymphocytic infiltration, and EB encoding region in situ hybridization demonstrated that 10-20% of the lymphocytes were EBV-infected. Drip and rest treatment improved the patient's liver enzymes, and her symptoms resolved. Repeat EGD after two months revealed improved gastric erosions. Here, we report a case of EBV-associated gastritis that was discovered due to perigastric lymphadenopathy accompanied by infectious mononucleosis. This report includes a review of the literature because a few studies reported EBV-associated gastritis.
Subject(s)
Epstein-Barr Virus Infections , Gastritis , Hepatitis, Viral, Human , Infectious Mononucleosis , Lymphadenopathy , Humans , Female , Adult , Infectious Mononucleosis/complications , Herpesvirus 4, Human , Epstein-Barr Virus Infections/complications , Lymphadenopathy/etiology , Lymphadenopathy/complications , Gastritis/etiology , Gastritis/diagnosis , Antibodies, ViralABSTRACT
BACKGROUND: Methylglyoxal (MGO) is a known toxic byproduct of glycolysis, with MGO-induced cytotoxicity believed to contribute to the pathogenesis of several diseases. Glyoxalase I (GLO1) is a key enzyme for eliminating MGO in mammalian cells, therefore, compounds affecting GLO1 activity are potential therapeutic agents for MGO-induced disorders. Previously, we found nordihydroguaiaretic acid (NDGA) as a potent GLO1 inhibitor. METHODS: The inhibitory characteristics of NDGA were determined spectrophotometrically with recombinant GLO1. NDGA-induced growth-inhibition and accumulation of MGO-derived advanced glycation end products (AGEs) were examined in EA.hy926 cells. RESULTS: NDGA showed significant inhibition of GLO1 enzymatic activity in a dose-dependent manner. Its Ki value was estimated to be 146-fold lower than that of myricetin, a known GLO1 inhibitor. The co-addition of MGO with NDGA to the cells resulted in significant growth inhibition, suggesting that MGO accumulation, sufficient to affect cell growth, was caused by NDGA inhibiting GLO1. These findings were supported by the observations that the addition of aminoguanidine, a typical MGO scavenger, significantly reversed cell-growth inhibition by co-addition of MGO with NDGA, and that an increase in intracellular MGO-derived AGEs was observed during incubation with the co-addition of MGO with NDGA. CONCLUSION: NDGA was found to be a novel and potent inhibitor of GLO1. The co-addition of NDGA with MGO to the cells resulted in increased intracellular MGO accumulation followed by enhanced cell-growth inhibition.
Subject(s)
Lactoylglutathione Lyase , Masoprocol , Pyruvaldehyde , Cell Proliferation , Lactoylglutathione Lyase/antagonists & inhibitors , Magnesium Oxide , Masoprocol/pharmacology , Pyruvaldehyde/metabolism , Humans , Cell LineABSTRACT
KEY POINTS: We investigated the mechanisms underlying faster force recovery from eccentric contractions (ECCs) in female than in male mice, focusing on mitochondrial responses. At 3 days after repeated ECCs (REC3), female mice showed faster recovery from ECC-induced force depression than male mice. At REC3, the mitochondria in females displayed superior responses to those in males: (i) mitochondrial Ca2+ uniporter content of muscles at REC3 was higher than that of rested muscles in females, and (ii) mitochondrial volume density in females was higher than that in males at REC3. Ovariectomized (OVX) female mice showed lower mitochondrial responses at REC3, similar to those observed in male mice, but oestrogen replacement nullified such lower responses in OVX. We concluded that: (i) superior mitochondrial responses after ECCs, at least in part, cause faster force recovery from ECCs in females than in males, and (ii) oestrogen contributes to such superior responses in the mitochondria in females. ABSTRACT: The purpose of this study was to investigate the mechanisms underlying sex differences in force recovery after eccentric contractions (ECCs). The left limbs of female and male mice were exposed to repeated ECCs (five sets of 50 contractions) elicited in vivo in the plantar flexor muscles. Isometric torques were measured before, immediately and at 3 days after ECCs (REC3), and gastrocnemius muscles obtained at REC3 were used for biochemical and morphological analyses. At REC3, a greater torque depression at 40 Hz was observed in males than females. Additionally, the following differences were observed at REC3: (i) in males but not females, triad structure was distorted, (ii) mitochondrial Ca2+ uniporter (MCU) content was increased in females but not in males, and (iii) mitochondrial volume density at REC3 was lower in males than in females. To examine the contribution of oestrogen to torque recovery, female mice were assigned to sham-operated (Sham), ovariectomized (OVX) and OVX treated with 17ß-oestradiol (OVX + E2) groups. At REC3, (i) greater torque depression at 40 Hz was observed in the OVX group than in the Sham and OVX + E2 groups, (ii) MCU content was increased in the Sham and OVX + E2 groups but not the OVX group, and (iii) mitochondrial volume density at REC3 was lower in the OVX group than the Sham and OVX + E2 groups. These results suggest that faster force recovery in females than in males is, at least partly, ascribable to superior mitochondrial responses, and oestrogen supplementation, in part, enhances such responses.
Subject(s)
Muscle Contraction , Muscle, Skeletal , Animals , Estradiol/pharmacology , Estrogens , Female , Male , Mice , TorqueABSTRACT
Heat stress, via its effects on muscle intracellular Ca2+ concentrations ([Ca2+]i), has been invoked as a putative therapeutic countermeasure to type 1 diabetes-induced muscle atrophy. Using a circulation- and neurally intact in vivo muscle preparation, we tested the hypothesis that impaired muscle Ca2+ homeostasis in type 1 diabetic rats is due to attenuated heat stress tolerance mediated via transient receptor potential vanilloid 1 (TRPV1). Male Wistar rats were randomly assigned to one of the following four groups: 1) healthy control 30°C (CONT 30°C); 2) CONT 40°C; 3) diabetes 30°C (DIA 30°C); and 4) DIA 40°C. The temperature of 40°C was selected because it exceeds the TRPV1 activation threshold. Spinotrapezius muscles of Wistar rats were exteriorized in vivo and loaded with the fluorescent Ca2+ probe Fura-2 AM. [Ca2+]i was estimated over 20 min using fluorescence microscopy (340/380 nm ratio) in quiescent muscle held at the required temperature, using a calibrated heat source applied to the ventral muscle surface. Western blotting was performed to determine the protein expression levels of TRPV1 in spinotrapezius muscle. After 20 min of heat stress, the CONT 40°C condition induced a 12.3 ± 5% [Ca2+]i (P < 0.05) elevation that was markedly absent in the DIA 40°C or other conditions. Thus, no significant differences were found among DIA 40°C, DIA 30°C, and CONT 30°C. TRPV1 protein expression was decreased by 42.0 ± 9% in DIA compared with CONT (P < 0.05) and, unlike CONT, heat stress did not increase TRPV1 phosphorylation. In conclusion, diabetes suppresses TRPV1 protein expression and function and inhibits the elevated myocyte [Ca2+]i evoked normally by heat stress. These results suggest that capsaicin or other therapeutic strategies to increase Ca2+ accumulation via TRPV1 might be more effective than hyperthermic therapy for type 1 diabetic patients.
Subject(s)
Calcium/metabolism , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 1/metabolism , Heat Stress Disorders/metabolism , Muscle, Skeletal/metabolism , TRPV Cation Channels/metabolism , Animals , Blood Glucose/metabolism , Capsaicin/pharmacology , Diabetes Mellitus, Experimental/physiopathology , Diabetes Mellitus, Type 1/physiopathology , Heat Stress Disorders/physiopathology , Homeostasis , Male , Muscle, Skeletal/drug effects , Muscle, Skeletal/physiopathology , Phosphorylation , Rats, Wistar , TRPV Cation Channels/agonists , Time FactorsABSTRACT
Peripheral artery disease (PAD) in the lower limb compromises oxygen supply due to arterial occlusion. Ischemic skeletal muscle is accompanied by capillary structural deformation. Therefore, using novel microscopy techniques, we tested the hypothesis that endothelial cell swelling temporally and quantitatively corresponds to enhanced microvascular permeability. Hindlimb ischemia was created in male Wistar rat's by iliac artery ligation (AL). The tibialis anterior (TA) muscle microcirculation was imaged using intravenously infused rhodamine B isothiocyanate dextran fluorescent dye via two-photon laser scanning microscopy (TPLSM) and dye extravasation at 3 and 7 days post-AL quantified to assess microvascular permeability. The TA microvascular endothelial ultrastructure was analyzed by transmission electron microscopy (TEM). Compared with control (0.40 ± 0.15 µm3 × 106), using TPLSM, the volumetrically determined interstitial leakage of fluorescent dye measured at 3 (3.0 ± 0.40 µm3 × 106) and 7 (2.5 ± 0.8 µm3 × 106) days was increased (both P < 0.05). Capillary wall thickness was also elevated at 3 (0.21 ± 0.06 µm) and 7 (0.21 ± 0.08 µm) days versus control (0.11 ± 0.03 µm, both P < 0.05). Capillary endothelial cell swelling was temporally and quantitatively associated with elevated vascular permeability in the AL model of PAD but these changes occurred in the absence of elevations in protein levels of vascular endothelial growth factor (VEGF) its receptor (VEGFR2 which decreased by AL-7 day) or matrix metalloproteinase. The temporal coherence of endothelial cell swelling and increased vascular permeability supports a common upstream mediator. TPLSM, in combination with TEM, provides a sensitive and spatially discrete technique to assess the mechanistic bases for, and efficacy of, therapeutic countermeasures to the pernicious sequelae of compromised peripheral arterial function.
Subject(s)
Capillary Permeability/physiology , Ischemia/physiopathology , Microscopy, Confocal , Muscle, Skeletal/blood supply , Animals , Hindlimb/physiopathology , Ligation/methods , Microcirculation/physiology , Microscopy, Confocal/methods , Microvessels/physiopathology , Neovascularization, Physiologic/physiology , Rats, WistarABSTRACT
The effect of cooling on in vivo intracellular calcium ion concentration [Ca2+]i after eccentric contractions (ECs) remains to be determined. We tested the hypothesis that cryotherapy following ECs promotes an increased [Ca2+]i and induces greater muscle damage in two muscles with substantial IIb and IIx fiber populations. The thin spinotrapezius (SPINO) muscles of Wistar rats were used for in vivo [Ca2+]i imaging, and tibialis anterior (TA) muscles provided greater fidelity and repeatability of contractile function measurements. SPINO [Ca2+]i was estimated using fura 2-AM and the magnitude, location, and temporal profile of [Ca2+]i determined as the temperature near the muscle surface post-ECs was decreased from 30°C (control) to 20°C or 10°C. Subsequently, in the TA, the effect of post-ECs cooling to 10°C on muscle contractile performance was determined at 1 and 2 days after ECs. TA muscle samples were examined by hematoxylin and eosin staining to assess damage. In SPINO, reducing the muscle temperature from 30°C to 10°C post-ECs resulted in a 3.7-fold increase in the spread of high [Ca2+]i sites generated by ECs (P < 0.05). These high [Ca2+]i sites demonstrated partial reversibility when rewarmed to 30°C. Dantrolene, a ryanodine receptor Ca2+ release inhibitor, reduced the presence of high [Ca2+] sites at 10°C. In the TA, cooling exacerbated ECs-induced muscle strength deficits via enhanced muscle fiber damage (P < 0.05). By demonstrating that cooling post-ECs potentiates [Ca2+]i derangements, this in vivo approach supports a putative mechanistic basis for how postexercise cryotherapy might augment muscle fiber damage and decrease subsequent exercise performance.
Subject(s)
Calcium/metabolism , Cold Temperature , Muscle Contraction/physiology , Muscle, Skeletal/physiology , Animals , Male , Rats , Rats, WistarABSTRACT
Ruthenium complexes are very useful phosphorescent probes for the visualization of hypoxia. We designed and synthesized three ruthenium complexes possessing bromopyrene, naphthalene, or anthracene units to improve the oxygen response. These ruthenium complexes provided strong phosphorescence under hypoxic conditions, while an increase in oxygen concentration led to a decrease in phosphorescence intensity. Among the ruthenium complexes, that with a bromopyrene unit (Ru-BrPy) had the best properties. This showed good cellular uptake and bright emission in cells, and had the highest sensitivity for molecular oxygen. Thus, Ru-BrPy is a promising candidate as a molecular probe for detecting cellular hypoxia.
Subject(s)
Coordination Complexes/chemistry , Fluorescent Dyes/chemistry , Oxygen/chemistry , Pyrenes/chemistry , Ruthenium/chemistry , A549 Cells , Cell Hypoxia , Cell Survival/drug effects , Coordination Complexes/metabolism , Coordination Complexes/toxicity , Fluorescent Dyes/metabolism , Humans , Microscopy, Fluorescence , Oxygen/analysisABSTRACT
Exercise increases the expression of brain-derived neurotrophic factor (BDNF) in the brain and contributes to cognitive and sensorimotor functions. This study aimed to elucidate how repeated exercise modifies BDNF expression elicited by a single bout of exercise in the brain using in vivo bioluminescence imaging (BLI). Bdnf-luciferase (Luc) mice with the firefly luciferase gene inserted at the translation start point of the Bdnf gene were used for BLI to monitor changes in BDNF expression in the brain. The treadmill exercise at a speed of 10 m/s for 60 min was repeated 5 days a week for 4 weeks. BLI in individual subjects was repeated four times: before the exercise intervention, on the first exercise day, and 14 and 28 days after the start of the intervention. Each BLI was performed after a single bout of exercise and monitored for 8 h after exercise. Repetitive BLI showed that the exercise regimen enhanced BDNF expression in the brain, specifically at 4-8 h after a single bout of exercise. Repeated exercise for 2 weeks accelerated the start of enhancement after a single bout of exercise, but not after 4 weeks of repeated exercise. This study showed that repeated exercise modulated the time window of exercise-enhanced BDNF expression, suggesting that repeated exercise could change the sensitivity of gene expression to a single bout of exercise. These findings can be attributed to the advantages of in vivo BLI, which allowed us to precisely measure the time course of BDNF expression after repeated exercise in individual subjects.
Subject(s)
Brain-Derived Neurotrophic Factor , Brain , Luminescent Measurements , Physical Conditioning, Animal , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/genetics , Animals , Physical Conditioning, Animal/physiology , Physical Conditioning, Animal/methods , Brain/metabolism , Luminescent Measurements/methods , Male , Mice , Time Factors , Mice, Inbred C57BLABSTRACT
Epigenetic regulation is involved in post-stroke neuroplasticity. We investigated the effects of intracerebral hemorrhage (ICH) on histone acetylation and gene expression related to neuronal plasticity in the bilateral sensorimotor cortices, which may affect post-stroke sensorimotor function. Wistar rats were randomly divided into the SHAM and ICH groups. We performed ICH surgery stereotaxically based on the microinjection of a collagenase solution in the ICH group. Foot fault and cylinder tests were performed to evaluate motor functions at 4-time points, including pre-ICH surgery. The amount of acetyl histones and the mRNA expression of neurotrophic factors crucial to neuroplasticity in the bilateral sensorimotor cortices were analyzed approximately 2 weeks after ICH surgery. Sensorimotor functions of the ICH group were inferior to those of the SHAM group during 2 weeks post-ICH. ICH increased the acetylation of histone H3 and H4 over the sham level in the ipsilateral and contralateral cortices. ICH increased the mRNA expression of IGF-1, but decreased the expression of BDNF compared with the sham level in the ipsilateral cortex. The present study suggests that histone acetylation levels are enhanced in bilateral sensorimotor cortices after ICH, presenting an altered epigenetic platform for gene expressions related to neuronal plasticity.
Subject(s)
Epigenesis, Genetic , Sensorimotor Cortex , Rats , Animals , Histones/metabolism , Rats, Wistar , Acetylation , Cerebral Hemorrhage/genetics , Cerebral Hemorrhage/metabolism , Sensorimotor Cortex/metabolism , RNA, Messenger/metabolismABSTRACT
Physical exercise increases brain-derived neurotrophic factor (BDNF) expression in the brain. However, the absence of non-invasive and repetitive monitoring of BDNF expression in the brains of living animals has limited the understanding of how BDNF expression changes after exercise. This study aimed to elucidate the temporal dynamics of BDNF expression in the brain after a single bout of exercise, using in vivo bioluminescence imaging. This study included Bdnf-Luc mice with a firefly Luciferase gene inserted at the translation start site of the mouse Bdnf gene. BDNF expression was evaluated based on the luminescence signal of the luciferase substrate administered to mice. Bioluminescence imaging was performed at 0, 1, 3, 6, 12, and 24 h after treadmill exercise (15 m/min for 1 h). Compared to the sedentary condition of each mouse, the luminescence signal increased by approximately 60 % between 1 and 3 h after exercise. The luminescence signal remained slightly increased by approximately 20 % even 6-24 h after exercise. This study is the first to demonstrate exercise-enhanced BDNF expression in the brains of living animals. These results provide evidence that a single bout of exercise transiently increases BDNF expression in the brain within a limited time window.
Subject(s)
Brain-Derived Neurotrophic Factor , Physical Conditioning, Animal , Mice , Animals , Brain-Derived Neurotrophic Factor/metabolism , Brain/metabolism , Genes, ReporterABSTRACT
Aseptic abscesses are rare extraintestinal manifestations of inflammatory bowel disease. Herein, we present the case of a 69-year-old female patient with ulcerative colitis in whom multiple aseptic abscesses were successfully treated with infliximab. Aseptic abscesses associated with ulcerative colitis are difficult to differentiate from infectious abscesses. In the present case, we reached a diagnosis of aseptic abscesses associated with ulcerative colitis as antibiotics were ineffective and repeated Gram stains and cultures of blood and abscess were negative. Aseptic abscesses are commonly found in the spleen, lymph nodes, liver, and skin; however, in the present case, the periosteum was the major site. Prednisolone is often effective for aseptic abscesses; however, the present patient was initially treated with a combination of 40 mg/day of prednisolone and granulocyte and monocyte adsorption apheresis, with inadequate effect. Infliximab was administered as the patient was steroid-resistant, with strong effect. Subsequently, infliximab treatment has been continued, with no recurrence after 2 years. However, as there have been reports of cases of recurrence even after remission with treatment, careful follow-up in the future is therefore necessary.
Subject(s)
Colitis, Ulcerative , Inflammatory Bowel Diseases , Female , Humans , Aged , Colitis, Ulcerative/complications , Colitis, Ulcerative/drug therapy , Infliximab/therapeutic use , Abscess/etiology , Abscess/complications , Inflammatory Bowel Diseases/complications , PrednisoloneABSTRACT
We studied the preventive effects of heat or cold therapy after repeated eccentric contraction against torque reduction, muscle soreness, and range of motion (ROM) due to delayed-onset muscle soreness (DOMS). A total of 42 healthy male subjects were randomly allocated into three groups: the HEAT group received heat therapy using an ultra-short-wave device; the ICE group received ice therapy using an ice pack; the Control group received no intervention. The measurements included maximal voluntary isometric, concentric, and eccentric elbow flexion torque, elbow extension ROM, pressure pain threshold, and muscle soreness with stretching muscle thickness and echo intensity. The measurements were taken before (pre), after (post), after (t-post), one-four days after, and seven days after the muscle damage protocol. The results showed the main effect of time on all measurements, but no significant interactions were observed. The results of this study suggest that heat or cold therapy in the first 30 min after intense eccentric exercise is insufficient to exert a preventive effect against DOMS.
ABSTRACT
Transcranial static magnetic field stimulation (tSMS) has inhibitory neuromodulatory effects on the human brain. Most of the studies on static magnetic fields have been performed in vitro. To further understand the biological mechanisms of tSMS, we investigated the effects of in vivo tSMS on motor behavior in normal awake rats. The skull of a male Wistar rat was exposed and a polyethylene tube was attached to the skull using dental cement at the center of the motor cortex (nâ¯=â¯7) or the other cortex (nâ¯=â¯6). By attaching a cylindrical NdFeB neodymium magnet into the tube, in vivo tSMS (REAL) was performed. For SHAM, we applied a similar size non-magnetic stainless-steel cylinder. All rats received twice each SHAM and REAL stimulation every two days using a crossover design, and motor function was measured during the stimulation. Activity level and asymmetry of forelimb use were not affected, but less accurate movements in the horizontal ladder test were found in REAL stimulation of the motor cortex. This study shows that in vivo tSMS has inhibitory neuromodulatory effects on motor behavior depending on the stimulated region on the rat cortex.
Subject(s)
Motor Activity/radiation effects , Motor Cortex/radiation effects , Stroke Rehabilitation/methods , Transcranial Magnetic Stimulation/methods , Animals , Evoked Potentials, Motor/physiology , Evoked Potentials, Motor/radiation effects , Feasibility Studies , Humans , Male , Models, Animal , Motor Activity/physiology , Motor Cortex/physiopathology , RatsABSTRACT
Exercise is recognized to increase the expression of neurotrophic genes in the hippocampus and prevent cognitive impairment. Histone deacetylase (HDAC) inhibitor acetylate histones and enhance gene transcription in epigenetic regulation. HDAC inhibitors are expected to be an efficacious pharmacological treatment for cognitive function. This study aimed to examine the effect of HDAC inhibitors and exercise on epigenetic markers and neurotrophic gene expression in the hippocampus to find a more enriched brain conditioning for cognitive function based on the synergic effects of pharmacological treatment and behavioral therapy. Thirteen-week-old male mice were divided into four groups. Intraperitoneal administration of an HDAC inhibitor (1.2 g/kg sodium butyrate, NaB) and treadmill exercise (approximately 10 m/min for 60 min) were performed 5 days a week for 4 weeks. NaB administration increased the expression of an immediate-early gene, a neurotrophin, and a neurotrophin receptor in the hippocampus. These results indicate that HDAC inhibition could present an enriched platform for neuronal plasticity in the hippocampus and cognitive function. The novel object recognition test showed that NaB administration increased the score. Notably, the step-through passive avoidance test showed improved learning and memory in the presence of exercise and exercise, indicating that the mice acquired fear memory, specifically in the presence of NaB administration plus exercise. This study found that repetitive administration of HDAC inhibitors improved cognitive function and HDAC inhibitor administration plus exercise has a synergic effect on learning and memory, accompanying the enhancement of crucial gene transcriptions for neuronal plasticity in the hippocampus.
Subject(s)
Gene Expression/drug effects , Hippocampus/drug effects , Hippocampus/metabolism , Histone Deacetylases/drug effects , Memory/drug effects , Neuronal Plasticity/drug effects , Animals , Brain-Derived Neurotrophic Factor/metabolism , Butyric Acid/pharmacology , Cognition/drug effects , Cognition/physiology , Epigenesis, Genetic/drug effects , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/metabolism , Male , Mice , Physical Conditioning, Animal/physiologyABSTRACT
We investigated sex differences in mitochondrial Ca2+ handling properties in mouse fast-twitch skeletal muscle. Changes in cytoplasmic Ca2+ concentration ([Ca2+]cyto) were measured in vivo using tibialis anterior muscles from male and female mice. The muscles were exposed to increasing concentrations of cyclopiazonic acid [CPA; sarcoplasmic reticulum (SR) Ca2+-ATPase inhibitor] (from 10 to 30 to 50 µM at 10 min intervals). Thirty minutes after treatment, [Ca2+]cyto was increased by 31.6 ± 2.0% and 13.5 ± 4.5% of initial [Ca2+]cyto in male and female muscles, respectively, and there was a significant difference between sexes. However, muscle preincubation for 5 min with 10 µM carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (an inhibitor of mitochondria Ca2+ uptake) eradicated this difference between sexes with respect to the CPA-induced [Ca2+]cyto increase. Both intermyofibrillar mitochondrial number and volume, assessed in longitudinal fiber sections, were higher in females compared with males (mitochondria number: 13.1 ± 1.0 in males vs. 19.9 ± 2.3 in females; mitochondrial volume: 0.034 ± 0.004 µm3/µm3 fiber volume in males vs. 0.066 ± 0.008 µm3/µm3 fiber volume in females, both P < 0.05). There were no sex differences in the content of SR Ca2+-ATPase, mitochondrial Ca2+ uniporter, mitofusin (Mfn) 1, or Mfn2. These results suggest that 1) mitochondrial Ca2+ uptake ability is greater in female than male myocytes, and 2) this superior Ca2+ uptake ability of female myocytes is due, partly, to the higher intermyofibrillar mitochondrial content but not to the expression of mitochondrial proteins related to mitochondrial Ca2+ uptake.NEW & NOTEWORTHY This investigation presents evidence that female versus male fast-twitch muscle exhibits a greater mitochondrial calcium ion uptake capability that is partly conferred by the higher intermyofibrillar mitochondrial volume density.
Subject(s)
Calcium/physiology , Muscle Fibers, Fast-Twitch/physiology , Sarcoplasmic Reticulum/physiology , Sex Characteristics , Animals , Female , Male , Mice , MitochondriaABSTRACT
Heat stress promotes intramyocyte calcium concentration ([Ca2+]i) accumulation via transient receptor potential vanilloid 1 (TRPV1) channels. We tested the hypothesis that muscle contractile activity concomitant with heat stress would accelerate the increase in [Ca2+]i via TRPV1, further impairing [Ca2+]i homeostasis. Spinotrapezius muscles of adult Wistar rats were exteriorized in vivo and loaded with the fluorescent Ca2+ probe fura 2-AM. Heat stress (muscle surface temperature 40°C) was used as TRPV1 activator. An isometric contraction (100 Hz, 5-10 V, 30 s) was induced electrically concomitant with heat stress. [Ca2+]i was determined for 20 min using in vivo fluorescence microscopy, and the phosphorylation response of TRPV1 was determined by Western blotting. Heat stress induced a significant [Ca2+]i increase of 18.5 ± 8.1% at 20 min and TRPV1 phosphorylation (+231%), which was inhibited by addition of the TRPV1 inhibitor (capsazepine). However, contrary to expectations, the heat stress and isometric contraction condition almost completely inhibited TRPV1 phosphorylation and the consequent [Ca2+]i elevation (<2.8% accumulation during heat stress, P > 0.05). In conclusion, this in vivo physiological model demonstrated that isometric muscle contraction(s) can suppress the phosphorylation response of TRPV1 and maintain [Ca2+]i homeostasis during heat stress. NEW & NOTEWORTHY This investigation is the first document the dynamics of intramyocyte calcium concentration ([Ca2+]i) increase in the myoplasm of skeletal muscle fibers in response to heat stress where the muscle blood flow is preserved. Heat stress at 40°C drives a myoplasmic [Ca2+]i accumulation in concert with transient receptor potential vanilloid 1 (TRPV1) phosphorylation. However, muscle contraction caused TRPV1 channel deactivation by dephosphorylation of TRPV1. TRPV1 inactivation via isometric contraction(s) permits maintenance of [Ca2+]i homeostasis even under high imposed muscle temperature.
Subject(s)
Calcium/metabolism , Heat-Shock Response/drug effects , Muscle Contraction/drug effects , TRPV Cation Channels/antagonists & inhibitors , Animals , Capsaicin/analogs & derivatives , Capsaicin/pharmacology , Heat Stress Disorders/drug therapy , Heat Stress Disorders/metabolism , Isometric Contraction/drug effects , Male , Muscle Fibers, Skeletal/metabolism , Phosphorylation/drug effects , Rats , Rats, WistarABSTRACT
BACKGROUND: Gait dysfunction associated with spasticity and hyperreflexia is a primary symptom in patients with compression of cervical spinal cord. The objective of this study was to link maximum compression ratio (CR) to spatiotemporal/pedobarographic parameters. METHODS: Quantitative gait analysis was performed by using a pedobarograph in 75 elderly males with a wide range of cervical compression severity. CR values were characterized on T1-weighted magnetic resonance imaging (MRI). Statistical significances in gait analysis parameters (speed, cadence, stride length, step with, and toe-out angle) were evaluated among different CR groups by the non-parametric Kruskal-Wallis test followed by the Mann-Whitney U test using Bonferroni correction. The Spearman test was performed to verify correlations between CR and gait parameters. RESULTS: The Kruskal-Wallis test revealed significant decline in gait speed and stride length and significant increase in toe-out angle with progression of cervical compression myelopathy. The post-hoc Mann-Whitney U test showed significant differences in these parameters between the control group (0.45Subject(s)
Gait Disorders, Neurologic/etiology
, Gait/physiology
, Spinal Cord Compression/complications
, Aged
, Cervical Vertebrae
, Gait Disorders, Neurologic/diagnosis
, Gait Disorders, Neurologic/physiopathology
, Humans
, Magnetic Resonance Imaging
, Male
, Middle Aged
, Spinal Cord Compression/diagnostic imaging
, Spinal Cord Compression/physiopathology