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A Irintchev

Publications and source records attributed to A Irintchev.

27 records · Page 2Linked to original sources
PubMed1991

Formation of new muscle fibres and tumours after injection of cultured myogenic cells.

We examined the effects of implantation of cultured myogenic cells from a permanent cell line into soleus muscles of histocompatible adult mice. Myogenic cells (10(6) or 10(4)) were implanted into intact muscles, muscles frozen with liquid nitrogen, paralysed with botulinum toxin or reinnervated after long-term (seven months) denervation. Formation of numerous muscle fibres in myogenic cell-injected muscles raised the total number of fibres up to ten times above control by four weeks. Larger effects were found in freeze-damaged than in paralysed muscles. The new fibres had small calibers, considerable length (greater than 1.3 mm, maximum distance over which serial sections were made), were multinucleated and were oriented parallel to the large-diameter fibres of the host muscles. In some experiments beta-galactosidase, introduced into myogenic cells via retroviral transfection, was detected in small and large muscle fibres 4-20 weeks after implantation, indicating survival of the grafted cells and formation of mosaic (host-donor) and new fibres of donor origin. Muscle weight increased significantly and, rather surprisingly, a parallel increase was found in isometric tetanic tension of isolated nerve-muscle preparations; thus tension per mg muscle tissue was not different from normal. By eight weeks reduction of acetylcholine sensitivity and down-regulation of neural cell adhesion molecule to normal were observed, indicating that synaptic transmission at the new fibres was mature. After different periods of time (5-20 weeks, depending on the subclone used) tumours developed in most but not all injected limbs (37 out of 39). The tumours were destructive to the muscles and were classified as rhabdomyosarcomas. Prior to tumour formation, neural cell adhesion molecule positive cells reappeared in the muscles; since the myogenic cells initially produced differentiated muscle fibres, it appears that malignant growth is induced by factors in vivo. Thus, at present the outcome of such implantation is unpredictable.

Acetylcholinesterase↗
PubMed1991

Axonal sprouting and changes in fibre types after running-induced muscle damage.

We have recently observed increase in Type I fibres in mouse soleus--but not extensor digitorum longus--muscles as a result of repeated muscle damage induced by voluntary wheel running. The most likely mechanism underlying the changes in fibre type composition is a redistribution of motor units with axonal sprouting and formation of new synapses. To test this hypothesis we exercised mice on a motor-driven treadmill once (3 x 3 h with 30 min rest periods in between, 14 m min-1, slope 6 degrees) or repeatedly (8-10 times at intervals of 3-5 days) and quantified axonal sprouting after staining with zinc iodide-osmium. In the contralateral solei, muscle damage and fibre type changes were evaluated with standard histochemical techniques. Significant numbers of damaged muscle fibers were found 0-15 days after a single exercise as compared to unexercised control animals (range 0.0-0.3% of the fibres in sedentary, n = 5, vs 2.1-14.8% in exercised muscles, n = 10) and repeated damage occurred in repeatedly exercised animals. In muscles of sedentary animals 3.8 +/- 1.4% SD of the examined endplates (n = 880, 5 muscles) had nodal or terminal sprouts. The incidence of sprouting was significantly elevated 3-21 days after a single exercise (7.5 +/- 1.8%, n = 2855, 12 muscles, P less than 0.01 signed-rank test), and more so after repeated running (12.0 +/- 2.5%, n = 1505, 6 muscles, P less than 0.01). Fibre type distributions were not different from controls 3 weeks after a single running episode, but after the 6-7 weeks of repeated running a significant increase in undifferentiated fibres at the cost of Type II fibres was found (9.7 +/- 3.4% versus 1.0 +/- 0.5% in sedentary controls, P less than 0.05, t-test); undifferentiated fibres express both Type I and Type II myofibrillar ATPase and are considered as fibres in the process of changing their types. These observations strongly support the assumption that sprouting and formation of new synapses--followed by motor unit enlargement and redistribution--occur as a result of muscle damage.

Animals↗
PubMed1991

Effects on recovery of soleus and extensor digitorum longus muscles of prolonged wheel running during a period of repeated nerve damage.

The right sciatic nerve in NMRI mice was frozen under anaesthesia 13 times at three-week intervals for a total period of 8.5 months. During this period, but not afterwards, one sub-group of these mice had access to running wheels in which the animals ran several kilometres per night, thereby actively or passively training reinnervated or denervated leg muscles, as well as the intact contralateral muscles. A number of distinct effects persisted for as long as 14-18 weeks after the termination of this "endurance training". In reinnervated soleus muscle, tetanic force was significantly higher (37%) in the trained muscles as was muscle weight (36%); in general, negative effects of the nerve damage persisted. In the reinnervated extensor digitorum longus, tetanic force and muscle weight were significantly smaller in the trained animals (by 11 and 16%, respectively) which are considered typical effects of endurance training. The resistance of the soleus neuromuscular junction to block by both curare and Mg2+ was depressed on the damaged side but this property was not influenced by the training; in extensor digitorum longus the pattern was similar. It is concluded that training during the period of repeated cycles of denervation-reinnervation produced significant effects which impressively outlasted the training period. The possible nature of these effects is discussed.

Animals↗
PubMed1991

Effects of enhanced activity on synaptic transmission in mouse extensor digitorum longus muscle.

1. Transmitter release at neuromuscular junctions of extensor digitorum longus (EDL) muscle in mice was studied after 2-8 month periods of unforced running in wheels. 2. Intracellular recordings at 10 Hz stimulation revealed that the quantal content of endplate potentials (EPPs) in Mg(2+)-blocked preparations was larger by 30% in trained (mean number of quanta, m = 1.75 +/- 0.19, n = 7) than in untrained control EDL muscles (m = 1.35 +/- 0.35, n = 7). Similarly the amplitudes of the first, maximum and plateau EPPs during tetanic stimulation (100 Hz for 1 s or 400 ms) in curare-blocked preparations were increased by 28% each; muscle fibre diameters did not differ while other postsynaptic effects were not excluded. 3. Training effects became particularly evident in two pairs of monozygotic twins, in which the time courses of facilitation and depression were changed as well: at 100 Hz stimulation the maximum EPP amplitude was reached on average at 2.6 impulses in controls but at 2.0 impulses in runners, and the following decline below the value of the first EPP at 5.0 and 3.8 impulses respectively. 4. Block resistance, as monitored by isometric tension measurements in different presynaptic (Mg2+) and postsynaptic (curare) blocking solutions, was higher in trained than in control EDL muscles. Depression in a train of four nerve-evoked single twitches at 2 Hz was lower. 5. As expected from the unchanged fibre diameters (see above) isometric tetanic force was similar in trained and control EDL muscles. Muscle fatigue resistance was larger in trained animals and succinic dehydrogenase activity was higher in fibres of trained muscles indicating an endurance training of the EDL muscle. 6. It is concluded that besides changes in muscle fibre properties, prolonged elevated activity causes increased transmitter release in EDL muscles. As a consequence, the safety margin of transmission in trained EDL muscles is markedly elevated.

Animals↗
PubMed1990

Reinnervation and recovery of mouse soleus muscle after long-term denervation.

Reinnervation and recovery of the mouse soleus muscle were studied 2-10 months after denervation periods of about 7 months. To maintain denervation the right sciatic nerve was frozen 14 times at 2-week intervals. Though initially intermittent muscle reinnervation occurred, contractile force of denervated muscles was reduced to less than 10% of the contralateral muscles by the fifth nerve freezing and further declined thereafter. Following reinnervation, recovery of soleus muscle force proceeded slowly to reach plateau values after 5-6 months. Tetanic muscle force reached on average 72% (range 58-86%, n = 12) of contralateral muscles after 5-10 months, (P less than 0.01, t-test for absolute values) and 87% of unoperated animals after 10 months (P less than 0.05, n = 5). Muscle fibre diameters were significantly reduced in reinnervated muscles, but frequency distributions were normal and similarly shaped in reinnervated and control muscles, suggesting complete muscle reinnervation and the absence of denervated fibres even at 2 months of reinnervation. Total numbers of muscle fibres were similar in reinnervated (842 +/- 73 S.D., n = 15), contralateral (854 +/- 104 S.D., n = 15) and control soleus muscles (853 +/- 77 S.D., n = 5). The number of myelinated axons in regenerating soleus nerves reached control values by 3 months after the last freezing, continued to increase till 6 months (150% of control), and declined thereafter (125% at 9-10 months). In the contralateral soleus nerves the number of myelinated axons remained constant during this period. Nerve fibre diameters remained abnormally small; even after 10 months of reinnervation fibre diameters were unimodally distributed with a mean diameter of 3.3 microns in contrast to the bimodal distribution in intact nerves (mean values 3.9 and 9.0 microns, respectively). Total fibre cross-section area per nerve increased with time but reached only 54% +/- 6 S.D., (n = 3) of contralateral nerves by 10 months. The relative thickness of the myelin sheath (g-ratio) returned to normal after 9-10 months. Anatomically, muscle reinnervation appeared to be complete by 7-8 weeks since unusually small muscle fibre profiles were absent.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1990

Muscle injury, cross-sectional area and fibre type distribution in mouse soleus after intermittent wheel-running.

1. It was previously noticed that mouse soleus, but not extensor digitorum longus (EDL) muscles, suffer fibre damage at the onset of voluntary wheel-running without further injuries thereafter. 2. In CBA/J mice trained continuously for 5 months and rested for periods of 1, 2, 3, 4 and 5 weeks acute muscle damage was found in soleus 7 days after the resumption of wheel-running. On single cross-sections damage was present on average in 8.7 +/- 3.5% (mean +/- S.D., n = 15) of the fibres, but only in 0.47 +/- 0.21% (n = 9) and 1.3 +/- 1.1% (n = 4) in control animals rested for 0-6 weeks after continuous running or in untrained controls. 3. Repeated muscle damage occurred when mice exercised for 4 days at intervals of 21-25 days, and after thirteen running episodes within 12 months marked changes in soleus, but not EDL muscles, were present. In cross-sections the total number of muscle fibre profiles was significantly larger in soleus of intermittent runners (768 +/- 68, n = 6; P less than 0.05), compared to continuous runners (676 +/- 54, n = 3) and sedentary animals (683 +/- 33, n = 4). This is probably due to incomplete repair which results in 'split fibres'. 4. At the same time total muscle fibre cross-sectional area was significantly elevated in intermittent runners (P less than 0.05), mainly due to increase in fibre diameters. Net cross-sectional areas were 0.59 +/- 0.069 mm2 (n = 6) in intermittent, 0.53 +/- 0.076 mm2 (n = 3) in continuous runners and 0.46 +/- 0.031 mm2 (n = 3) in sedentary controls. 5. Tetanic and twitch force were also significantly elevated in soleus of intermittent runners while the ratio force/area remained the same. 6. There was an increase in the proportion of type I fibres in soleus from 75 +/- 0.9% (n = 4) in untrained controls to 90 +/- 4.4% (n = 6; P less than 0.05) in intermittent runners and 81 +/- 5.6% (n = 3; n.s.) in continuous runners. 7. Resistance to block of synaptic transmission in soleus was significantly higher in intermittent runners for two levels of curare, indicating enhanced safety margins. 8. EDL muscles in intermittent runners were not different from sedentary controls in any of the parameters studied. In particular, muscle fibres with signs of previous damage (split fibres, central nuclei) were rare (on average 0.5-0.6%) and equally frequent in all experimental groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Prolonged running does not improve muscle coordination after cross-union of tibial and peroneal nerves in mice.

Several months after cross-union of the tibial and peroneal nerves and full muscle reinnervation motor behavior was monitored and was tested by electromyographic recordings from both musculus tibialis anterior (TA) and musculus gastrocnemius medialis (MG). In addition spinal motoneuron pools were labelled by injecting wheat-germ agglutinin-horseradish peroxidase (WGA-HRP) into experimental and control TA muscles. Though the location of TA motoneurons was similar in all 9 mice tested and suggested successful cross-reinnervation, running behavior and EMG patterns varied remarkably. In some animals the alternating activities of TA and MG muscles remained more or less clearly separated from each other but were out of phase with the running cycle. A somewhat better motor behavior was accompanied by simultaneous activity in both muscles. Voluntary running in wheels for several kilometers per day did not visibly improve motor coordination indicating the absence of activity-related synaptic readjustments.

Animals↗
PubMed1987

Muscle damage and repair in voluntarily running mice: strain and muscle differences.

Soleus, extensor digitorum longus and tibialis anterior muscles of mice voluntarily running in wheels for periods of 5 to 120 days were studied in spaced serial and serial cross-sections. Shortly after the onset of running and during the next 2 weeks, degeneration, necrosis, phagocytosis and regeneration of muscle fibers, satellite cell proliferation and cellular infiltration were found in soleus muscles of mice from all strains investigated (CBA/J, NMRI, C57bl, NIH, SWS and Balb/c). Tibialis anterior but not extensor digitorum longus muscles were also damaged. Predominantly high-oxidative fibers were affected (both slow-oxidative and fast oxidative glycolytic in soleus, fast-oxidative glycolytic in tibialis anterior). Denervated soleus muscles that had been passively stretched during running were not damaged. Evidence was found that, during the early period of running, split fibers form by myogenesis within (regeneration) or outside (satellite cell proliferation) necrotic muscle fiber segments. Split fibers persisted in solei of long-term (2 to 3 months) exercised CBA/J but not NMRI mice. In 6 out of 20 solei of CBA/J runners exercised for 2 months or longer, fiber-type grouping was observed in the areas where extensive damage usually occurred in the early periods. The results show that different muscles are damaged and repaired to varying degrees and that marked interstrain and inter-individual differences are present. It appears that acute muscle injury occurring upon onset of voluntary running is a usual event in the adaptation of muscles to altered use.

Animals↗