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Biomedical subjects

I Uramoto

Publications and source records attributed to I Uramoto.

At least 19 recordsLinked to original sources
PubMed2001

A possible role for BDNF, NT-4 and TrkB in the spinal cord and muscle of rat subjected to mechanical overload, bupivacaine injection and axotomy.

Neurotrophins play a crucial role in the regulation of survival and the maintenance of specific functions for various populations of neurons. Neurotrophin-4 (NT-4) is most abundant in skeletal muscle, and is thought to promote sciatic nerve sprouting, inhibit agrin-induced acetylcholine receptor (AChR) clustering, evoke postsynaptic potentiation and induce mitochondrial proliferation. Using Western blot analysis, immunoprecipitation and immunohistochemistry, we investigated the distribution of NT-4 in slow- and fast-type muscles. We also tested the adaptive response of this protein in the mechanically overloaded muscle, in the regenerating muscle following bupivacaine injection and in the denervated muscle. Additionally, we investigated whether TrkB phosphorylation in the spinal cord and in the sciatic nerve occurs through the interaction with BDNF or NT-4 when the innervating muscle is damaged. Markedly more NT-4 was expressed in fast-type muscles compared with the slow types. TrkB protein was more frequently observed around the edge of myofibers (neuromuscular junction) of the soleus muscle compared with the gastrocnemius muscle. TrkB tyrosine phosphorylation occurred in the spinal cord but not in the sciatic nerve 24 h after bupivacaine injection of the innervating muscle. At the same time, the amount of TrkB co-precipitating with BDNF was markedly increased in the spinal cord. A rapid activation of TrkB (1-8 h) was also observed in the spinal cord after axotomy,while the amount of TrkB co-precipitating with NT-4 was markedly lower after axotomy. These results indicate that NT-4 is preferentially distributed in fast-type muscles. Furthermore, by interacting with BDNF and NT-4, the TrkB in the spinal cord may be important for the survival of motoneurons and outgrowth of injured peripheral axons following muscle damage.

Animals↗
PubMed2001

[A plastic property in the change of rat muscle potentials clarified in the presence of neostigmine: a conjecture on the recycling process of ACh].

Released acetylcholine (ACh) is rapidly hydrolyzed, and choline is recaptured and re-used as available ACh for release. This elaborated recycling process of ACh was evaluated in terms of muscle potentials evoked by a set of 10 stimuli in the presence and the absence of neostigmine using Wistar rats anesthetized with urethane. All potentials evoked by a set of 10 stimuli before the injection of neostigmine were similar in amplitude. The first potential recorded 8 min after it was as large as that before it. The second potential was greatly depressed, and others were gradually recovered to the control level. The recovery was attained in the 5th-7th potential in some rats while a slight depression of the 10th potential was still seen in other animals. This time course was a general pattern in the change of muscle potentials evoked by a set of 10 stimuli in the presence of neostigmine. When 10 stimuli were given 9 min after it, all potentials showed rather comparable amplitudes to the control level. Thus, another pattern was found. The two patterns were repeatedly observed within individuals: A striking contrast in the changing pattern was noted between successive two sets of 10 stimuli with an interval of one minute. The former set exerted an influence upon those muscle potentials evoked by the latter one beyond one minute or so, but this effect disappeared during the elapse of two minutes or more. This plastic property and other findings were discussed in conjunction with those evidences recently accumulated on the recycling process of ACh. A conjecture was made on the recycling process of ACh: The process would be activated following impulse transmission, and this activation would be maintained for one minute or so. In that sense, this process would be controlled in a 'short-term memory' manner and endocytosis of synaptic vesicles coupled with their exocytosis should be emphasized. In addition, releasable ACh would be restored during repetitive stimulation even if it was once depleted notably.

Acetylcholine↗
PubMed2000

Differential adaptation of growth and differentiation factor 8/myostatin, fibroblast growth factor 6 and leukemia inhibitory factor in overloaded, regenerating and denervated rat muscles.

Mice genetically deficient in growth and differentiation factor 8 (GDF8/myostatin) had markedly increased muscle fiber numbers and fiber hypertrophy. In the regenerating muscle of mice possessing FGF6 mutation, fiber remodeling was delayed. Although myostatin and FGF6 may be important for the maintenance, regeneration and/or hypertrophy of muscle, little work has been done on the possible role of these proteins in adult muscle in vivo. Using Western blot and immunohistochemical analysis, we investigated, in rats, the distribution of myostatin, FGF6 and LIF proteins between slow- and fast-type muscles, and the adaptive response of these proteins in mechanically overloaded muscles, in regenerating muscles following bupivacaine injection and in denervated muscles after section of the sciatic nerve. The amounts of myostatin and LIF protein were markedly greater in normal slow-type muscles. In the soleus muscle, myostatin and LIF proteins were detected at the site of the myonucleus in both slow-twitch and fast-twitch fibers. In contrast, FGF6 protein was selectively expressed in normal fast-type muscles. Mechanical overloading rapidly enhanced the myostatin and LIF but not FGF6 protein level. In the regenerating muscles, marked diminution of myostatin and FGF6 was observed besides enhancement of LIF. Denervation of fast-type muscles rapidly increased the LIF, but decreased the FGF6 expression. Therefore, the increased expressions of myostatin and LIF play an important role in muscle hypertrophy following mechanical overloading. The marked reduction of FGF6 in the hypertrophied and regenerating muscle would imply that FGF6 regulates muscle differentiation but not proliferation of satellite cells and/or myoblasts.

Animals↗
PubMed2000

Postnatal profiles of myogenic regulatory factors and the receptors of TGF-beta 2, LIF and IGF-I in the gastrocnemius and rectus femoris muscles of dy mouse.

The dystrophin-deficient mdx mouse presents muscle fiber necrosis but active muscle regeneration, probably due to an extensive recruitment of myogenic regulatory factors (MRF), several growth factors and cytokines, and favorable interaction of satellite cells. In contrast, the laminin alpha 2 (merosin)-deficient dy mouse shows progressive muscle fiber necrosis and ineffective muscle regeneration. Using Western blot and immunohistochemical analyses, we investigated the adaptive changes in MRF, growth factors and cytokines and their receptors in the muscles of dy mice during postnatal growth. The relative volume of MyoD, myogenin and Myf-5 proteins was markedly lower in the gastrocnemius and rectus femoris muscles of dy mice. Transforming growth factor-beta 2, leukemia inhibitory factor (LIF) and basic fibroblast growth factor were not up-regulated in the muscles of dy mice. The levels of the LIF receptor and insulin-like growth factor-I receptor levels were markedly decreased in the muscles of dy mice during the entire postnatal period observed in this study. Therefore, unlike the situation in mdx mice, the milieu of regeneration following repetitive damage seems to be degraded in the muscles of dy mice.

Aging↗
PubMed2000

The adaptive response of transforming growth factor-beta 2 and -beta RII in the overloaded, regenerating and denervated muscles of rats.

Using a muscle cell line and satellite cell cultures, it has been shown that transforming growth factor-beta (TGF-beta) has a powerful inhibitory effect on myoblast replication and differentiation. However, little work has been done on the possible role of TGF-beta in adult muscle in vivo. Using Western blot and immunohistochemical analyses, we investigated normal distribution of TGF-beta 2 and TGF-beta RII proteins between slow and fast-type muscles, and the adaptive response of these proteins in the mechanically overloaded muscles, in the regenerating muscles following bupivacaine injection and in the denervated muscle after section of sciatic nerve. Slight TGF-beta 2 immunoreactivity was detected both in slow- and fast-type muscles of mature rat. The amount of TGF-beta RII protein was markedly greater in fast-type muscles. In the overloaded muscle, immunohistochemical analysis showed a marked increase in TGF-beta 2 immunoreactivity in the mononuclear cells (probably endothelial and perithelial or smooth muscle cells of endomysial capillaries) of the extracellular space at 3 and 6 days post surgery. Rapid increase of TGF-beta 2 protein and concomitant decrease of the receptor (TGF-beta RII) were observed in the mechanically overloaded and regenerating muscles. On the other hand, denervation of slow- and fast-type muscles showed a rapid increase in TGF-beta 2 protein, but did not elicit a concomitant decrease of TGF-beta RII. These results indicate that TGF-beta RII is preferentially distributed in fast-type muscles. Furthermore, TGF-beta 2 may play an important role in muscle hypertrophy and regeneration by the usage of TGF-beta RII.

Animals↗
PubMed1999

The adaptive response of MyoD family proteins in overloaded, regenerating and denervated rat muscles.

Using Western blot analysis, we investigated whether the amount of myogenic regulatory factors differs in slow-type and fast-type muscles. In addition, we examined the adaptive response of myogenic regulatory factor protein in the overloaded rat muscles by the ablation of synergists, in the regenerating muscles following bupivacaine injection and in the denervated muscle. The amount of myogenin protein in the slow-type muscle was markedly greater. In contrast, the proteins MyoD and Myf-5 were selectively accumulated in the fast-type muscles. A gradual down-regulation of MyoD and Myf-5 proteins was detected in the denervated fast-type muscles, but not in the myogenin protein content. A rapid down-regulation of myogenic regulatory factor protein was observed both of the mechanically overloaded and in the regenerating muscles. These results indicate that the fast-type-specific gene expression in muscle is modulated by MyoD and Myf-5 proteins and suggest that myogenin protein plays an important role in the reconstruction of damaged neuromuscular connections.

Adaptation, Physiological↗
PubMed1998

Muscular dystrophy: centronucleation may reflect a compensatory activation of defective myonuclei.

Muscular dystrophy has long been believed to be characterized by degeneration and abortive regeneration of muscle fibers (the muscle degeneration theory), but unfortunately its pathogenesis is still unclear and an effective treatment has yet to be developed. As a challenge to the theory, we have proposed an alternative muscle-defective-growth theory and a further bone muscle growth imbalance hypothesis supposing possible defects in bone-growth-dependent muscle growth based on our findings in hereditary dystrophic dy mice (C57BL/6J dy/dy). This review presents some new insights into the pathogenesis of the disease along with our hypothesis, focusing on the physiological meaning of centronucleation, one of the major pathological changes commonly observed in dystrophic muscles of man and experimental animals.

Animals↗
PubMed1998

Differential adaptations of insulin-like growth factor-I, basic fibroblast growth factor, and leukemia inhibitory factor in the plantaris muscle of rats by mechanical overloading: an immunohistochemical study.

We investigated changes in several growth factors in the rat plantaris muscle produced by mechanical overloading by ablation of synergists using immunohistochemistry. At 1 and 3 days post surgery, the insulin-like growth factor-I (IGF-I) level was slightly increased in the cytosol and markedly increased in the invading cells of the extracellular space. Thereafter, the IGF-I immunoreactivity evoked by overloading rapidly decreased to the normal level. The level of leukemia inhibitory factor (LIF), which was not shown to change at 1 day post surgery, was increased in the cytosol at 3, 5, 7 and 10 days and at 2 weeks. Basic fibroblast growth factor (bFGF) immunoreactivity did not change during the entire period of overloading (1 day-3 weeks post surgery). These results indicate that the elevations of the levels of IGF-I and LIF show differential time course in the plantaris muscle subjected to functional overload. Furthermore, bFGF appears not to be related to the compensatory hypertrophy produced by overloading.

Adaptation, Physiological↗
PubMed1998

Recycling of acetylcholine following impulse transmission in rat muscle revealed in the presence of neostigmine.

1. The recycling process of acetylcholine (ACh) following impulse transmission was studied in terms of muscle potentials evoked by repetitive stimulation in the presence of neostigmine. 2. Wistar rats were anaesthetized with urethane and muscle potentials were recorded with concentric electrodes from their exposed medial gastrocnemius muscles before and after the injection of neostigmine. 3. All potentials before neostigmine treatment were similar in amplitude. A set of 10 stimuli was given at 0.5 Hz 6-8 min after drug administration. The first potential was as large as that before it. The second potential was greatly depressed. Thereafter, potentials gradually recovered. 4. Two sets of 10 stimuli were delivered at a 1 min interval (i.e. with a 40 s rest period between them). The second potential was not depressed so severely in the second set as in the first set. The same procedure was repeated in some rats and the aforementioned phenomenon was noted. When two sets of 10 stimuli were given at an interval of 2 min or more, the second potential was equally depressed in the both sets of stimuli. 5. The recycling of ACh following impulse transmission in the junctional region was revealed in terms of muscle potentials in the presence of neostigmine. This process was activated due to repetitive stimulation. Moreover, the activated state seemed to be maintained for a while after the cessation of stimuli. These results suggest the possible existence of a neural mechanism that can exert an influence on the recycling of ACh following impulse transmission beyond a short period of time.

Acetylcholine↗
PubMed1998

Developmental changes of impulse transmission in rat gastrocnemius muscles revealed by neostigmine.

Developing rats between 5 and 44 days of age as well as rats about 2 months old were anesthetized with urethane. Spontaneous activities and muscle potentials to sciatic stimuli were recorded from their exposed medial gastrocnemius muscles using concentric electrodes. Neostigmine of 0.12-0.40 mg/kg was injected into the contralateral muscles. Regardless of age, spontaneous activities were not observed and muscle potentials were evoked by single stimuli primarily in a biphasic wave (main component) before the drug treatment. Developmental differences were revealed in the presence of the drug. 1) Spontaneous activities were detected only in single spikes around postnatal 10 days. Single or double spikes were often found in rats of about two weeks. Burst discharges such as seen in adult rats were observed immediately before weaning. 2) In rats of 2 weeks or so, one or more components were observed obscurely following the main component of muscle potentials, which appeared definitely at the preweaning period. 3) When double shocks with the interval of 2 sec were delivered in the presence of the drug, the second potential was greatly depressed in rats older than two weeks as well as in adult rats. The potential was only slightly reduced in rats around 10 days. Thus, an adult pattern as to impulse transmission was observed immediately before weaning. These alterations would, at least in part, reflect the maturation of acetylcholine receptors at neuromuscular junctions.

Action Potentials↗
PubMed1995

[Postnatal development of evoked potentials in the rat somatosensory cortex].

The developmental changes of evoked potentials in the somatosensory cortex were studied using Long-Evans rats of postnatal age from day 2 to day 55. A hole of appropriate size was made in the skull under urethane anesthesia (1.4 g/kg) and somatosensory evoked potentials (SEPs) were recorded with a silver-ball electrode. Electrical stimulation was applied to whisker C 3 follicle. The electrode was moved on the dura over the hemisphere and SEPs were displayed on an oscilloscope. When a maximum SEP was obtained 100 successive responses were digitally processed with a time resolutions of 100 microseconds and averaged. From the averaged SEP, various peak latencies and amplitudes were calculated. In response to electrical stimulation of the whisker follicle, a short-latency positive wave appeared on postnatal day 2 (PND 2) and the second positive wave was recorded on PND 8 and a negative wave appeared on PND 10. The latency of these waves shortened, while the amplitude increased with age. SEPs in developing rats attained adult pattern on PND 17, although both the values of latency and amplitude reach the limit on PND 55. The placing reaction was also tested from PND 9 to PND 15 to examine the functional development of whisker. All subjects displayed positive placing reaction of chin hair on PND 10. At this age all components appeared in the SEP, 1st positive, 2nd positive and negative waves.

Aging↗
PubMed1993

A possible interpretation for difference in neostigmine-induced changes of spontaneous activities and evoked muscle potentials between rat medial gastrocnemius and soleus muscles.

1. Under urethane-anaesthesia, changes of spontaneous activities and evoked muscle potentials in rat medial gastrocnemius (MG) and soleus (SOL) muscles induced by the injection of neostigmine were investigated. 2. Before the administration of neostigmine, spontaneous activities were rarely observed and muscle potentials evoked by single shocks were simply biphasic in both MG and SOL muscles. When the anti-cholinesterase drug was applied, spontaneous discharges of motor units were often observed in bursts in the MG muscles, in contrast to single spikes in the SOL muscles. The biphasic wave of evoked potentials in the MG muscles was followed by one or more oscillations, which were scarcely observed in the SOL muscles. These burst discharges and oscillations in the MG muscles [corrected] also occurred even after transection of the sciatic nerve proximal to the stimulating site. 3. A late component with a small amplitude could be observed in the evoked potentials of MG and SOL muscles. It was potentiated in amplitude after the administration of the drug. 4. Prolonged action of acetylcholine (ACh) has been known to occur in the presence of anticholinesterase drugs, and this was taken into account for the mechanism of the phenomena proposed in the present study. Contrasting changes between MG and SOL muscles were observed, which may be explained by different modes of ACh release in the MG and SOL muscles.

Animals↗
PubMed1986

Age-related changes in the content and composition of glycosaminoglycans isolated from the mouse skeletal muscle: normal and dystrophic conditions.

Glycosaminoglycans were isolated from the skeletal muscle of either normal or dystrophic mice aged from 3 to 18 weeks. The glycosaminoglycan content of the normal muscle, based on the tissue weight, decreased slightly during the period from 3 to 10 weeks, and remained almost unchanged after 10 weeks. The major glycosaminoglycan in normal muscle was hyaluronate, the relative amount of which increased slightly (from 70% to 80%) with age. Both dermatan sulfate and heparan sulfate were also obtained. The relative amounts of these sulfated glycosaminoglycans tended to decrease with age. On the other hand, the glycosaminoglycan content of the dystrophic muscle was higher than that of normal muscle even at 3 weeks. The proportion of hyaluronate was almost constant (about 65%) throughout the age range examined. The relative amount of dermatan sulfate increased from 20% to 30% with a compensatory decrease in the amount of heparan sulfate. Further, the incorporation of [35S]sulfate into glycosaminoglycans by the dystrophic muscle was reduced to about 60% of the normal. These differences in glycosaminoglycan composition and [35S]sulfate incorporation between the normal and the dystrophic muscles may be related to the progressive muscular dysfunction seen in this disease.

Aging↗
PubMed1985

Patterns of soleus muscle potentials to repetitive stimulation in young and aged rats.

Muscle potentials were recorded in the soleus muscle of Wistar rats anesthetized with urethane or Nembutal. The time course of their changes induced by repetitive stimulation of sciatic nerves at 5 Hz for 10 min was compared for young and aged rats. When stimulation commenced, muscle potentials from young rats were somewhat facilitated, followed by slight depression below control values, and thereafter they were gradually potentiated. On the contrary, muscle potentials from aged rats were rapidly reduced, attaining plateau levels 2 min or so after the onset of repetitive stimulation at 5 Hz.

Age Factors↗
PubMed1984

Differences among dystrophic, dwarf, and their crossbred mice in the time course of changes in extracellular muscle action potentials induced by 5-Hz stimulation.

With urethane anesthesia, extracellular action potentials were recorded in medial gastrocnemius muscles of dystrophic, dwarf, and their crossbred mice. When repetitive stimulation was delivered at 5 Hz for a relatively long period, characteristic features were revealed. (i) Dystrophic mice showed a slight decrease or even an increase in action potentials whereas in littermate normal mice the amplitudes were rapidly and notably reduced. (ii) In both dwarf and their littermate normal mice, a considerable reduction in amplitude was observed. Slightly more depression was produced than in nondystrophic mice of a comparable age. (iii) Crossbred mice were in two classes. A rapid and notable reduction in the amplitude of muscle action potentials was observed in one class, and slight changes in the potentials were produced in another class showing dystrophy-specific symptoms.

Action Potentials↗