Norikatsu Kasuga's research while affiliated with Aichi University of Education and other places

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Publications (50)


Figure 1. Intramuscular and surface EMG recordings from the denervated TA muscles during sciatic nerve stimulation after 1 week of denervation.
Figure 2. 3D images of the tibia. Trabecular bone at the metaphyseal section and cortical bone at the mid-diaphysis of the tibia were evaluated using micro-CT.
Figure 3. Immunofluorescence photomicrographs of tibialis anterior (TA) muscles for laminin (red) in the CON (A), DN (B), and DN+ES (C) groups, and quantification of mean myofiber cross-sectional area (FCSA) (D) and muscle force (E). Bar 50 μm. *P < 0.05 vs. CON; † P < 0.05 vs. DN. (CON, control; DN, sciatic nerve denervation; DN+ES, sciatic nerve denervation + electrical stimulation).
Figure 4. 3D images of trabecular bone at the analysis site of the tibiae (A), and the trabecular bone volume fraction (BV/TV, B), trabecular thickness (Tb.Th, C), trabecular number (Tb.N, D), connectivity density (Conn.D, E), and increased trabecular separation (Tb.Sp, F). *P < 0.05 vs. CON; † P < 0.05 vs. DN.
Figure 5. Representative 3D images of the tibia mid-diaphysis from micro-CT (upper panel) and representations of the load-displacement curves from CON, DN, and DN+ES rat tibiae loaded by three-point bending (lower panel). (CON, control; DN, sciatic nerve denervation; DN+ES, sciatic nerve denervation + electrical stimulation).

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Low-Frequency Electrical Stimulation of Denervated Skeletal Muscle Retards Muscle and Trabecular Bone Loss in Aged Rats
  • Article
  • Full-text available

June 2019

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58 Reads

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15 Citations

International Journal of Medical Sciences

Hiroyuki Tamaki

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Kengo Yotani

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Noriaki Yamamoto

Electrical stimulation (ES)-induced muscle contraction has multiple effects; however, mechano-responsiveness of bone tissue declines with age. Here, we investigated whether daily low-frequency ES-induced muscle contraction treatment reduces muscle and bone loss and ameliorates bone fragility in early-stage disuse musculoskeletal atrophy in aged rats. Twenty-seven-month-old male rats were assigned to age-matched groups comprising the control (CON), sciatic nerve denervation (DN), or DN with direct low-frequency ES (DN+ES) groups. The structural and mechanical properties of the trabecular and cortical bone of the tibiae, and the morphological and functional properties of the tibialis anterior (TA) muscles were assessed one week after DN. ES-induced muscle contraction force mitigated denervation-induced muscle and trabecular bone loss and deterioration of the mechanical properties of the tibia mid-diaphysis, such as the stiffness, but not the maximal load, in aged rats. The TA muscle in the DN+ES group showed significant improvement in the myofiber cross-sectional area and muscle force relative to the DN group. These results suggest that low-frequency ES-induced muscle contraction treatment retards trabecular bone and muscle loss in aged rats in early-stage disuse musculoskeletal atrophy, and has beneficial effects on the functional properties of denervated skeletal muscle.

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Representative cross-sectional images of tibialis anterior (TA) muscle immunostained for laminin (red) in Cont (a), DN (b), and DN + ES (c) groups, and quantification of mean myofiber cross-sectional area (FCSA) (d). Bar 100 μm. *P < 0.05, vs. Cont, †P < 0.05, vs. DN. Values are means ± SD. (Color figure online)
Representative 3D images of tibia mid-diaphysis from micro CT (upper panel) and representations of load–displacement curves from Cont, DN, and DN + ES rat tibiae loaded by three-point bending (lower panel)
Immunohistochemical staining for DMP1 (a–d) in cortical bone, average optical density of DMP1 immunoreactivity (e), and DMP1 positive area (f). Bar 50 μm. *P < 0.05, vs. Cont, †P < 0.05, vs. DN. Values are means ± SD
Electrical Stimulation of Denervated Rat Skeletal Muscle Ameliorates Bone Fragility and Muscle Loss in Early-Stage Disuse Musculoskeletal Atrophy

April 2017

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78 Reads

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13 Citations

Calcified Tissue International

We tested whether daily muscle electrical stimulation (ES) can ameliorate the decrease in cortical bone strength as well as muscle and bone geometric and material properties in the early stages of disuse musculoskeletal atrophy. 7-week-old male F344 rats were randomly divided into three groups: age-matched control group (Cont); a sciatic denervation group (DN); and a DN + direct electrical stimulation group (DN + ES). Denervated tibialis anterior (TA) muscle in the DN + ES group received ES with 16 mA at 10 Hz for 30 min/day, 6 days/week. Micro CT, the three-point bending test, and immunohistochemistry were used to characterize cortical bone mechanical, structural, and material properties of tibiae. TA muscle in the DN + ES group showed significant improvement in muscle mass and myofiber cross-sectional area relative to the DN group. Maximal load and stiffness of tibiae, bone mineral density estimated by micro CT, and immunoreactivity of DMP1 in the cortical bone tissue were also significantly greater in the DN + ES group than in the DN group. These results suggest that daily ES-induced muscle contraction treatment reduced the decrease in muscle mass and cortical bone strength in early-stage disuse musculoskeletal atrophy and is associated with a beneficial effect on material properties such as mineralization of cortical bone tissue.


Bone loss due to disuse and electrical muscle stimulation

September 2016

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473 Reads

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3 Citations

The Journal of Physical Fitness and Sports Medicine

The mass and structure of bone tissue adapt to the mechanical loads imparted by gravity and movement, and are controlled by the balance between bone formation and bone resorption. The primary adaptations of bone to disuse are demineralization and loss (thinning) of trabecular and cortical bone. Exercise training and electrical muscle stimulation (ES) induce adaptive changes in bone that improve bone strength and inhibit bone loss. ES has been generally applied to patients undergoing physical rehabilitation to maintain and/or recover muscle mass and force-generating capacity in disused muscles. ES-induced muscle contraction of disused muscle can also ameliorate deleterious post-disuse adaptation of bone. The mechanical effects of ES-induced muscle contraction are essential for the maintenance of bone mass and strength, which are achieved through the cooperative functions of osteocytes, osteoblasts, and osteoclasts. The effects of ES, however, are dependent on the stimulation paradigm, including the intensity, frequency, and number of stimuli and the duration of the intervention. This review summarizes the literature on the effects of ES-induced muscle contraction on disuse osteopenia.


Adaptative changes and contractile properties of skeletal muscle: Significance and problems of tension measurement

October 2015

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15 Reads

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1 Citation

The Journal of Physical Fitness and Sports Medicine

The contractile function of skeletal muscles is comprised of 3 major elements: strength (maximum muscle strength), speed (contractile velocity), and fatigue resistance (endurance). In sport science, the muscle contractile function facilitating exercise is a notable muscle function, and many studies have investigated the, training effects on skeletal muscle. In the sport science field, various training effects on skeletal muscle have been examined. For example, the level of protein forming the muscular microstructure and composition of muscle fiber type change. Recently, in skeletal muscle training experiments, correlation between changes in molecular and gene control systems in response to training have been attracting attention; however, few studies have simultaneously measured the contractile properties. In this review, the experimental significance of measuring the muscle contractile function has been outlined with reference to previous studies.


Figure 1. TA muscle force (A) and force-time integrals (B) induced by direct muscle electrical stimulation (ES) at an intensity of 16 mA at 10 Hz, and TA tetanic force (C) in ES intervention rats. Representative EMG recordings from the right contralateral and left denervated TA muscles during sciatic nerve stimulation after 1 week of denervation (D). Note that no significant differences are observed in muscle force output induced by the same condition with the daily ES regimen between the DN+ES and DN+ES+SM groups. No EMG recordings are observed in the denervated TA. Values are means ± SD. DN, denervation; SM, streptomycin treatment. 
Figure 4. Histomorphometric analyses for mean osteoid thickness (A), osteoid area (B), and osteocyte numbers embedded in the osteoid area (C), and a representative image of osteoid (D-H) following DN of 1 week. Micrographs show distinct eosinophilia of the osteoid matrix at trabecular bone stained with H-E and osteocytes embedded in osteoid (arrowhead in D and G). Bar = 50 μm *P< 0.05, vs CON, †P<0.05, vs ES. Values are means ± SD. 
Effect of electrical stimulation-induced muscle force and streptomycin treatment on muscle and trabecular bone mass in early-stage disuse musculoskeletal atrophy

September 2015

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222 Reads

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9 Citations

Journal of Musculoskeletal & Neuronal Interactions

Objectives: The aim was to determine whether daily muscle electrical stimulation (ES) and streptomycin treatment would have positive or negative effects on trabecular bone mass in disuse rats. Methods: Seven-week-old male F344 rats were randomly divided into five groups of eight animals each: an age-matched control group (CON); a sciatic denervation group (DN); a DN + direct electrical stimulation group (DN+ES); a DN + streptomycin treatment group (DN+SM); and a DN+ES+SM group. The tibialis anterior (TA) muscles in all ES groups were stimulated with 16mA at 10Hz for 30 min/day, six days/week, for one week. Bone volume and structure were evaluated using micro-CT, and histological examinations of the tibiae were performed. Results: Direct ES significantly reduced the disuse-induced trabecular bone loss. Osteoid thickness were also significantly greater in the ES groups than in the DN group. Micro CT and histomorphological parameters were significantly lower in the DN+ES+SM group than in the DN+ES group, while there were no significant differences between the DN and DN+SM groups. Conclusions: These results suggest that ES-induced muscle force reduced trabecular bone loss, and streptomycin treatment did not induce bone loss, but attenuated the effects of ES-induced muscle force on reducing the loss of disused bone.



Characteristics of the Localization of Connexin 43 in Satellite Cells during Skeletal Muscle Regeneration In Vivo

April 2015

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98 Reads

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7 Citations

Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry

For myogenesis, new myotubes are formed by the fusion of differentiated myoblasts. In the sequence of events for myotube formation, intercellular communication through gap junctions composed of connexin 43 (Cx43) plays critical roles in regulating the alignment and fusion of myoblasts in advances of myotube formation in vitro. On the other hand, the relationship between the expression patterns of Cx43 and the process of myotube formation in satellite cells during muscle regeneration in vivo remains poorly understood. The present study investigated the relationship between Cx43 and satellite cells in muscle regeneration in vivo. The expression of Cx43 was detected in skeletal muscles on day 1 post-muscle injury, but not in control muscles. Interestingly, the expression of Cx43 was not localized on the inside of the basement membrane of myofibers in the regenerating muscles. Moreover, although the clusters of differentiated satellite cells, which represent a more advanced stage of myotube formation, were observed on the inside of the basement membrane of myofibers in regenerating muscles, the expression of Cx43 was not localized in the clusters of these satellite cells. Therefore, in the present study, it was suggested that Cx43 may not directly contribute to muscle regeneration via satellite cells.





Citations (26)


... In this study, we investigated whether B-SES tetanus stimulation has a preventive effect on muscle atrophy. Denervation in rats results in significant reductions in muscle weight and CSA of both the TA and GAS muscles 2,27,28 . Compared with those in the CONT group, we observed significant reductions in muscle weight and CSA in the DEN group. ...

Reference:

Belt electrode tetanus muscle stimulation reduces denervation-induced atrophy of rat multiple skeletal muscle groups
Low-Frequency Electrical Stimulation of Denervated Skeletal Muscle Retards Muscle and Trabecular Bone Loss in Aged Rats

International Journal of Medical Sciences

... However, the interaction effect for CTX-I was significantly different between the groups, which can only be explained in terms of the influence of electric current and magnetic field. As electrical bone stimulation is known to promote osteogenesis in various experimental conditions (cell cultures, animals, and humans) (Cadossi et al. 2020;Tamaki et al. 2016), the significant interaction effect between the groups' CTX-1 was presumably related to the greater expression of osteoprotegerin and a higher ratio between osteoprotegerin and the receptor activator of the nuclear factor κB ligand (RANKL) in the ES group (Qin et al. 2013). ...

Bone loss due to disuse and electrical muscle stimulation

The Journal of Physical Fitness and Sports Medicine

... Strenuous ECC readily injures muscles. For instance, downhill running in rats has been shown to injure the plantaris muscles by attenuating contractility, which is accompanied by an inflammatory response that occurs within a few days, followed by the recovery of muscle contractility with fiber remodeling in a few weeks [8]. Augmented force stacked from each sarcomere impairs various possible extra-sarcomeric sites along the force transmitting pathway, such as the costamere, sarcolemma, neuromuscular junction, musculotendinous junction, and fascia. ...

Effects of downhill running incorporated into long-term endurance training on skeletal muscle fiber-type switching and fatigue resistance
  • Citing Article
  • July 2014

The Journal of Physical Fitness and Sports Medicine

... Consequently, these research findings facilitate more optimal utilization of diverse methods for denervated skeletal muscle atrophy treatment. Several treatment modalities are currently proposed, encompassing electrical stimulation (Dow et al., 2005;Tamaki et al., 2017) and noncoding RNA (He et al., 2016;Li et al., 2017;Hitachi et al., 2019). Furthermore, extensive utilization of various food and drug extracts is evident in the treatment of denervated skeletal muscle atrophy. ...

Electrical Stimulation of Denervated Rat Skeletal Muscle Ameliorates Bone Fragility and Muscle Loss in Early-Stage Disuse Musculoskeletal Atrophy

Calcified Tissue International

... The rats in the RWR group were exercised with minimum resistance (i.e., 4.5 g) for the first week, and then the resistance was progressively increased to reach 30% of their body weight during the 4 wk of exercise. A resistance of 30% of body weight in wheel running is sufficient to produce muscular adaptation similar to that of other exercises performed at 60% of body weight (23). Daily work levels (J) as total energy expenditure during exercise were calculated and expressed relative to body weight and day as follows: work ϭ force (N) ϫ distance (m)/body wt (kg)/day, where force is the resistance of the wheel, and distance is the number of revolutions times the circumference of the wheel. ...

Various in running pattern and skeletal muscle adaptations in voluntary running rats at different load

Japanese Journal of Physical Fitness and Sports Medicine

... The present reduction in Dm was ~ 10% less than that shown by Hunter et al. (2012), indicating the less severe form of EIMD that commonly occurs in early stages of resistance training (Damas et al. 2015). A plausible explanation for reduced Dm is the alteration of intra-muscular tissue fluid content (Kasuga 2015) known to occur with EIMD in the early stages of resistance training (Chen et al. 2012). Such a non-invasive marker of contractile function could be useful for practitioners to gain objective insight into the efficacy of training interventions in their early stages. ...

Adaptative changes and contractile properties of skeletal muscle: Significance and problems of tension measurement
  • Citing Article
  • October 2015

The Journal of Physical Fitness and Sports Medicine

... Maximal isometric contraction tension was measured separately in the Pre 2nd bout groups (Pre 2nd bout_1w, Pre 2nd bout_2w, and Pre 2nd bout_4w) each week after the first ECC intervention. Measurement was performed as previously described [32,33]. Briefly, under isoflurane anaesthesia, rats were placed on a working platform with restraining bars and pins at the knee and ankle joints. ...

Effect of electrical stimulation-induced muscle force and streptomycin treatment on muscle and trabecular bone mass in early-stage disuse musculoskeletal atrophy

Journal of Musculoskeletal & Neuronal Interactions

... The transfection of skeletal muscle primary cultures with dominant negative Cx43 confirmed that the activity of this protein is needed for myoblast proliferation and syncytial fusion into myotubes [85]. It was later found that in regenerating muscle, the cluster of differentiated satellite cells, which represent an advanced stage of fusion in the inner part of the basal membrane, do not express Cx43, confirming that this protein does not participate actively in myoblast fusion, although it is required for the initiation of this process [86]. ...

Characteristics of the Localization of Connexin 43 in Satellite Cells during Skeletal Muscle Regeneration In Vivo

Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry

... In addition, it has been proposed that the effects of NMES on osteogenesis may be explained by the induction of mechanical and humoral factors due to electrostimulation muscle contractions. 36,37 According to Elnaggar et al., 7 these gains may be related to mechanical loading on the involved extremities, also contributing to improve the joint mobility and shoulder function outcome. ...

Electrical stimulation of denervated rat skeletal muscle retards trabecular bone loss in early stages of disuse musculoskeletal atrophy

Journal of Musculoskeletal & Neuronal Interactions

... HGF/c-Met pathway induces migration of hematopoietic progenitors and facilitates stress-induced mobilization from the bone marrow [35,107,108]. HGF/c-Met promotes chemotaxis of satellite cells as well [109][110][111][112][113], which is required for myoblast directional motility and myocyte fusion during adult skeletal muscle restoration [113]. ...

In Vivo Real-Time Imaging of Exogenous HGF-Triggered Cell Migration in Rat Intact Soleus Muscles

Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry