A Wireless 2-Channel Layered EMG/NIRS Sensor System for Local Muscular Activity Evaluation.

A wireless 2-channel layered sensor system that enables electromyography (EMG) and near-infrared spectroscopy (NIRS) measurements at two local positions was developed. The layered sensor consists of a thin silver electrode and a photosensor consisting of a photoemitting diode (LED) or photodiode (PD). The EMG and NIRS signals were simultaneously measured using a pair of electrodes and photosensors for the LED and PD, respectively. Two local muscular activities are presented in detail using layered sensors. In the experiments, EMG and NIRS signals were measured for isometric constant and ramp contractions at each forearm using layered sensors. The results showed that local muscle activity analysis is possible using simultaneous EMG and NIRS signals at each local position.

A Wireless Multi-Layered EMG/MMG/NIRS Sensor for Muscular Activity Evaluation.

A wireless multi-layered sensor that allows electromyography (EMG), mechanomyography (MMG) and near-infrared spectroscopy (NIRS) measurements to be carried out simultaneously is presented. The multi-layered sensor comprises a thin silver electrode, transparent piezo-film and photosensor. EMG and MMG measurements are performed using the electrode and piezo-film, respectively. NIRS measurements are performed using the photosensor. Muscular activity is then analyzed in detail using the three types of data obtained. In experiments, the EMG, MMG and NIRS signals were measured for isometric ramp contraction at the forearm and cycling exercise of the lateral vastus muscle with stepped increments of the load using the layered sensor. The results showed that it was possible to perform simultaneous EMG, MMG and NIRS measurements at a local position using the proposed sensor. It is suggested that the proposed sensor has the potential to evaluate muscular activity during exercise, although the detection of the anaerobic threshold has not been clearly addressed.

Enzymatically modified isoquercitrin supplementation intensifies plantaris muscle fiber hypertrophy in functionally overloaded mice.

BACKGROUND: Enzymatically modified isoquercitrin (EMIQ) is produced from rutin using enzymatic hydrolysis followed by treatment with glycosyltransferase in the presence of dextrin to add glucose residues. EMIQ is absorbed in the same way as quercetin, a powerful antioxidant reported to prevent disused muscle atrophy by targeting mitochondria and to have ergogenic effects. The present study investigated the effect of EMIQ on skeletal muscle hypertrophy induced by functional overload. METHODS: In Study 1, 6-week-old ICR male mice were divided into 4 groups: sham-operated control, sham-operated EMIQ, overload-operated control, and overload-operated EMIQ groups. In Study 2, mice were divided into 3 groups: overload-operated whey control, overload-operated whey/EMIQ (low dose), and overload-operated whey/EMIQ (high dose) groups. The functional overload of the plantaris muscle was induced by ablation of the synergist (gastrocnemius and soleus) muscles. EMIQ and whey protein were administered with food. Three weeks after the operation, the cross-sectional area and minimal fiber diameter of the plantaris muscle fibers were measured. RESULTS: In Study 1, functional overload increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. EMIQ supplementation significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle in both the sham-operated and overload-operated groups. In Study 2, EMIQ supplementation combined with whey protein administration significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. CONCLUSION: EMIQ, even when administered as an addition to whey protein supplementation, significantly intensified the fiber hypertrophy of the plantaris muscle in functionally overloaded mice. EMIQ supplementation also induced fiber hypertrophy of the plantaris in sham-operated mice.

Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle.

Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise.

Effect of AMPK activation on monocarboxylate transporter (MCT)1 and MCT4 in denervated muscle.

It is now evident that exercise training leads to increases in monocarboxylate transporter (MCT)1 and MCT4, but little is known about the mechanisms of coupling muscle contraction with these changes. The aim of this study was to investigate the effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) induced activation of AMP-activated protein kinase (AMPK) on MCT1, MCT4, and GLUT4 in denervated muscle. Protein levels of MCT4 and GLUT4 after 10 days of denervation were significantly decreased in mice gastrocnemius muscle, while MCT1 protein levels were not altered. AICAR treatment for 10 days significantly increased MCT4, and GLUT4 protein levels in innervated muscle as shown in previous studies. We found that the MCT1 protein level was also increased in AICAR treated innervated muscle. AICAR treatment prevented the decline in MCT4 and GLUT4 protein levels in denervated muscle. Thus, the current study suggests that MCT1 and MCT4 protein expression in muscles, as well as GLUT4, may be regulated by AMPK-mediated signal pathways, and AMPK activation can prevent denervation-induced decline in MCT4 protein.

Intrinsic ability of adult stem cell in skeletal muscle: an effective and replenishable resource to the establishment of pluripotent stem cells.

Adult stem cells play an essential role in mammalian organ maintenance and repair throughout adulthood since they ensure that organs retain their ability to regenerate. The choice of cell fate by adult stem cells for cellular proliferation, self-renewal, and differentiation into multiple lineages is critically important for the homeostasis and biological function of individual organs. Responses of stem cells to stress, injury, or environmental change are precisely regulated by intercellular and intracellular signaling networks, and these molecular events cooperatively define the ability of stem cell throughout life. Skeletal muscle tissue represents an abundant, accessible, and replenishable source of adult stem cells. Skeletal muscle contains myogenic satellite cells and muscle-derived stem cells that retain multipotent differentiation abilities. These stem cell populations have the capacity for long-term proliferation and high self-renewal. The molecular mechanisms associated with deficits in skeletal muscle and stem cell function have been extensively studied. Muscle-derived stem cells are an obvious, readily available cell resource that offers promise for cell-based therapy and various applications in the field of tissue engineering. This review describes the strategies commonly used to identify and functionally characterize adult stem cells, focusing especially on satellite cells, and discusses their potential applications.

Monitoring neurodegeneration in diabetes using adult neural stem cells derived from the olfactory bulb.

INTRODUCTION: Neurons have the intrinsic capacity to produce insulin, similar to pancreatic cells. Adult neural stem cells (NSCs), which give rise to functional neurons, can be established and cultured not only by intracerebral collection, which requires difficult surgery, but also by collection from the olfactory bulb (OB), which is relatively easy. Adult neurogenesis in the hippocampus (HPC) is significantly decreased in diabetes patients. As a result, learning and memory functions, for which the HPC is responsible, decrease. METHODS: In the present study, we compared the effect of diabetes on neurogenesis and insulin expression in adult NSCs. Adult NSCs were derived from the HPC or OB of streptozotocin-induced diabetic rats. Comparative gene-expression analyses were carried out by using extracted tissues and established adult NSC cultures from the HPC or OB in diabetic rats. RESULTS: Diabetes progression influenced important genes that were required for insulin expression in both OB- and HPC-derived cells. Additionally, we found that the expression levels of several genes, such as voltage-gated sodium channels, glutamate transporters, and glutamate receptors, were significantly different in OB and HPC cells collected from diabetic rats. CONCLUSIONS: By using identified diabetes-response genes, OB NSCs from diabetes patients can be used during diabetes progression to monitor processes that cause neurodegeneration in the central nervous system (CNS). Because hippocampal NSCs and OB NSCs exhibited similar gene-expression profiles during diabetes progression, OB NSCs, which are more easily collected and established than HPC NSCs, may potentially be used for screening of effective drugs for neurodegenerative disorders that cause malignant damage to CNS functions.

The insulin regulatory network in adult hippocampus and pancreatic endocrine system.

There is a very strong correlation between the insulin-mediated regulatory system of the central nervous system and the pancreatic endocrine system. There are many examples of the same transcriptional factors being expressed in both regions in their embryonic development stages. Hormonal signals from the pancreatic islets influence the regulation of energy homeostasis by the brain, and the brain in turn influences the secretions of the islets. Diabetes induces neuronal death in different regions of the brain especially hippocampus, causes alterations on the neuronal circuits and therefore impairs learning and memory, for which the hippocampus is responsible. The hippocampus is a region of the brain where steady neurogenesis continues throughout life. Adult neurogenesis from undifferentiated neural stem cells is greatly decreased in diabetic patients, and as a result their learning and memory functions decline. Might it be possible to reactivate stem cells whose functions have deteriorated and that are present in the tissues in which the lesions occur in diabetes, a lifestyle disease, which plagues modern humans and develops as a result of the behavior of insulin-related factor? In this paper we summarize research in regard to these matters based on examples in recent years.

Reduction of ribosome biogenesis with activation of the mTOR pathway in denervated atrophic muscle.

Mammalian target of rapamycin (mTOR) pathway positively regulates the cell growth through ribosome biogenesis in many cell type. In general, myostatin is understood to repress skeletal muscle hypertrophy through inhibition of mTOR pathway and myogenesis. However, these relationships have not been clarified in skeletal muscle undergoing atrophy. Here, we observed a significant decrease of skeletal muscle mass at 2 weeks after denervation. Unexpectedly, however, mTOR pathway and the expression of genes related to myogenesis were markedly increased, and that of myostatin was decreased. However, de novo ribosomal RNA synthesis and the levels of ribosomal RNAs were dramatically decreased in denervated muscle. These results indicate that ribosome biogenesis is strongly controlled by factors other than the mTOR pathway in denervated atrophic muscle. Finally, we assessed rRNA transcription factors expression and observed that TAFIa was the only factor decreased. TAFIa might be a one of the limiting factor for rRNA synthesis in denervated muscle.

Fundamental study of detection of muscle hypertrophy-oriented gene doping by myostatin knock down using RNA interference.

To investigate the feasibility of developing a method for detection of gene doping in power-athletes, we devised an experimental model system. Myostatin is a potent negative regulator of skeletal muscle development and growth, and myostatin-knockout mice exhibit a double-muscle phenotype. To achieve knockdown, we constructed plasmids expressing short hairpin interfering RNAs (shRNAs) against myostatin. These shRNAs were transfected into C2C12 cultured cells or injected into the tibialis anterior (TA) muscle of adult mice. By performing in vitro and in vivo experiments, we found that some shRNAs effectively reduced the expression of myostatin, and that the TA muscle showed hypertrophy of up to 27.9%. Then, using real-time PCR, we tried to detect the shRNA plasmid in the serum or muscles of mice into which it had been injected. Although we were unable to detect the plasmid in serum samples, it was detectable in the treated muscle at least four weeks after induction. We were also able to detect the plasmid in muscle in the vicinity of the TA. This gene doping model system will be useful for further studies aimed at doping control. Key pointsUsing a myostatin knockdown plasmid, we have succeeded in creating a model system for gene doping using mice that resulted in muscle hypertrophy greater than that reported previously.We confirmed that there was a limit of gene doping detection using real-time PCR, either from serum or muscle smple.This model experimental system can be utilized for examining indirect methods of gene doping detection such as immune responses to gene transfer or a profiling approach using DNA microarray.

Effects of citrulline supplementation on fatigue and exercise performance in mice.

During high-intensity exercise, the concentration of ammonia is augmented in skeletal muscle. Ammonia activates phosphofructokinase and prevents oxidation of pyruvate to acetyl CoA, thus leading to exhaustion. Citrulline is an amino acid component of the urea cycle in the liver, along with ornithine and arginine. The aim of this study was to examine the effect of citrulline supplementation on fatigue and performance during high-intensity exercise. We constructed a swimming exercise protocol, in which mice were subjected to exhaustive swimming with a load of 5% body weight, and measured the time until exhaustion, the blood levels of lactate and ammonia, and the glycogen content of the gastrocnemius and biceps femoris muscles. Citrulline supplementation significantly increased the swimming time until exhaustion. Exercise-induced blood ammonia elevation was repressed by citrulline supplementation, and exercise-induced blood lactate increment in the citrulline-supplemented group was significantly lower than that in the non-supplemented group. Citrulline supplementation may facilitate the detoxification of ammonia via the urea cycle and inhibit additional glycolysis. Our findings suggest that citrulline supplementation may be useful for improving the exercise performance of athletes.

Expression of monocarboxylate transporter (MCT) 1 and MCT4 in overloaded mice plantaris muscle.

A number of studies have shown that changes in muscle contractile activity regulate the expression of monocarboxylate transporters (MCTs) in the skeletal muscle. The aim of this study was to investigate the effect of functional overload on MCT1 and MCT4 protein expression. Plantaris muscles were functionally overloaded for 15 days by ablation of the synergistic muscles. MCT1 and MCT4 mRNA abundance increased by 160-161% (p < 0.01) and 265-325% (p < 0.05), respectively, after 1-3 days of functional overload. MCT1 and MCT4 protein expression increased by 92 and 61%, respectively, after 12 days of functional overload (p < 0.05). AMP-activated protein kinase (AMPK) phosphorylation status [phospho-AMPK (Thr172)/total AMPK] was significantly elevated after 3-9 days of functional overload. Plasma testosterone concentration was elevated after 12 days of functional overload, while blood lactate concentration was not altered. Thus, the current study demonstrated that heavy mechanical loading induces increase in MCT1 and MCT4 protein expression in the muscles with increase in AMPK phosphorylation status and plasma testosterone concentration.

Simple method for the identification of oxidative fibers in skeletal muscle.

Skeletal muscle is composed of several different types of myofiber: slow oxidative (SO), fast glycolytic oxidative and fast glycolytic. However, the classification is usually determined by myosin heavy chain typing rather than by metabolic index. In this study, the oxidative metabolic index was investigated as a possible method of myofiber typing. Myoglobin, which is involved in oxygen transport and storage in myofibers, and mitochondria, which are the central organelles for oxidative metabolism, were studied. High levels of myoglobin and mitochondria are believed to exist in SO fibers, but the current study showed that they are considerably richer in some fast type fibers. As myofiber typing using the oxidative metabolic index is important physiologically, an attempt was made to find a simple method for this purpose. Some mitochondrial proteins have been observed to auto-fluoresce but until now this effect was too faint to detect easily. Owing to the recent advances in cooling charge-coupled device technology, such auto-fluorescence can now be used for myofiber typing, and the simple and rapid method for doing so is reported here.