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A Wernig

Publications and source records attributed to A Wernig.

At least 55 records · Page 3Linked to original sources
PubMed1993

Differential expression of tenascin after denervation, damage or paralysis of mouse soleus muscle.

The expression of the extracellular matrix molecule tenascin was studied by immunocytochemistry and Western blotting in soleus muscles of adult mice after nerve damage (denervation), muscle injury (induced by enforced running or freezing) and functional block of synaptic transmission (botulinum toxin). Enhanced expression of tenascin in the extracellular spaces around focally damaged muscle fibres was found already 10 h after onset of running on a motor-driven treadmill which causes muscle injury in soleus muscle. Tenascin expression reached a peak at 2-3 days post-exercise, after which it declined gradually and became undetectable by two weeks after injury. Similarly, cryo-damage of soleus muscles in situ led to upregulation of tenascin. Chronic muscle denervation after sciatic nerve transection caused a persistent (studied up to 31 days) expression of tenascin at denervated endplates and in intramuscular nerve branches but not in other tissue compartments. Local application of botulinum toxin Type A, which results in muscle inactivity but not in tissue degeneration, however, did not induce tenascin expression 12 h to 12 days post-injection. Expression of tenascin after denervation and muscle damage, but its absence after paralysis, were verified by SDS-PAGE and Western blot analysis. Independent of the type of injury (muscle, nerve or both) the known major isoforms of mouse tenascin, as judged by M(r) comparison, were re-expressed, with no preponderance of individual M(r) forms. These results show that tenascin expression in adult muscles is induced by both axon and muscle fibre damage but not by muscle inactivity. In contrast, NCAM, in accordance with previous observations, showed enhanced expression both as a result of inactivity and in association with tissue repair.

Animals↗
PubMed1993

Acetylcholine receptor bars and transmitter release in frog neuromuscular junctions.

After labelling with rhodaminated alpha-bungarotoxin, acetylcholine receptors in cutaneous pectoris muscles of normal adult frogs (Rana temporaria) appear as brightly fluorescent straight bars, usually extending over the whole gutter. Here we investigated first whether receptor bars can undergo changes and secondly whether they would provide a structural correlate for the strength of a junction. Bars of low fluorescence intensity, as well as short or discontinuous receptor bars consisting of two or three segments, suggest plasticity at the receptor/active zone level. In order to elucidate this notion, receptor bars were studied at different seasons which have previously been shown to be associated with structural changes. In two groups of frogs kept under laboratory conditions simulating wintertime and summertime, respectively, the length and number of receptor bars and the amount of discontinuous bars were investigated. Synaptic contact length, which is the summed length of labelled synaptic branches, and the number and total length of receptor bars did not differ significantly. A clear difference between Group I ("winter" frogs) and Group II ("summer" frogs) was found in the number of discontinuous bars, which was almost twice as high in Group I compared with Group II (6.4 +/- 3.3% S.D. vs 3.4 +/- 1.3% S.D., n = 8 and 7 muscles, respectively, P < 0.05). In addition, the average length of individual bars was slightly longer in Group I frogs (2.16 +/- 0.7 micron S.D. vs 2.07 +/- 0.12 microns S.D., 0.1 < P < 0.05). Transmitter release has been shown to be different in these two groups--as determined from endplate potential measurements in tubocurarine-containing bathing solutions--although it was equal when measured in low Ca2+/high Mg2+ [Dorlöchter M. et al. (1991) Pflügers Arch. 418, Suppl. 1, R31]. We also investigated whether receptor bars would be a reasonable structural correlate of synaptic function by comparing different measures of transmitters release with different structural parameters in 19 identified junctions. The mean quantal content (m) of a junction was positively correlated with the number and total length of receptor bars, but not with synaptic contact area or length. Amplitudes of the first, maximum, and plateau endplate potentials (corrected for a common resting potential and apparent input resistance) at tetanic nerve stimulation (40 Hz for 2 s) in tubocurarine block were strongly correlated with both synaptic contact length and total receptor bar length (r = 0.90 for maximum endplate potential); correlations between m and any structural measure were significantly worse.(ABSTRACT TRUNCATED AT 400 WORDS)

Acclimatization↗
PubMed1992

Laufband locomotion with body weight support improved walking in persons with severe spinal cord injuries.

After low transection of the spinal cord mammalian quadrupeds can be trained to walk on a driven surface indicating that coordinating neuronal circuits persist in the spinal cord segments caudal to the lesion. We trained 8 persons with incomplete spinal cord lesion on a Laufband (driven treadmill) for 1 1/2 to 7 months (5 days a week, 30-60 minutes daily) starting 5 to 20 months after injury and found significant improvement in the utilisation of the paralysed limbs during locomotion. Locomotion is described in one additional patient who had trained independently on parallel bars for several years. Five patients had complete functional paralysis in one lower limb when tested in a resting position. In EMG recordings voluntary activity (ie activity induced upon command) was absent or residual in the main flexor and extensor muscles of this limb. In contrast, during locomotion flexion and extension movements were performed and phasic EMG activity was present. In these 5 patients, and in all others reported here, skin sensibility and proprioception are preserved to different degrees in all limbs. In the course of locomotive training of 4 severely paralysed patients the initially habituating flexion reflexes could be entrained in the paralysed limbs as was the case for knee extension during stance. Subsequently, initial body weight support (BWS) of 40% could be reduced to 0%. The distance covered on the Laufband (0-104 m in the first week) increased significantly (200-410 m) in the last week of training as did speed (0-10 to 14-23 m/min). More importantly, this training subsequently allowed patients to walk on a static surface for 100 to 200 meters while voluntary activity remained absent in the paralysed limb when tested at rest. Similar progress was achieved in the 4 less severely paralysed patients. The one patient who had trained independently on parallel bars for several years is described walking on a static surface for 40 meters with the help of a walker, though he had one completely and one near completely paralysed lower limb. It appears that bipedal stepping with consequent knee extension and stabilisation can be taught after unilateral complete or near complete loss of voluntary activity, suggesting the manifestation of complex reflex motor patterns at the spinal level.

Adult↗
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↗
PubMed1989

Maturation of transmission in reinnervated mouse soleus muscle.

After the tibial nerve of the mouse was cut unilaterally and immediately resutured, reinnervation of soleus muscle proceeded rapidly and muscle isometric contraction characteristics reached normal levels within 2 months. In contrast, synaptic transmission remained immature since resistance to presynaptic (magnesium) or postsynaptic (curare) blocking solutions remained reduced. Results suggest that release probability and transmitter stores were smaller than normal. To study the effect of training, animals were allowed to run in wheels. Running caused a delay in reinnervation at 18-20 days, which was, however, abolished by 4 weeks. On the other hand, exercise counteracted development of denervation atrophy. The safety margin of transmission in runners was higher than in nonrunners at 4 weeks, indicating enhanced maturation, but was lower at 2 months of reinnervation. These results suggest that recovery of muscle precedes maturation of synaptic transmission.

Animals↗
PubMed1989

Muscle fibre loss and reinnervation after long-term denervation.

Cutaneous pectoris muscles of frog (Rana temporaria) were investigated 19.5-40 months after denervation. On whole mounts a heavy reduction in size and number of muscle fibres is noticed; in two muscles studied with semithin and ultrathin sections the number of remaining muscle fibres is 149 and around 120, while one of the contralateral muscles contains 250 and control muscles of equal sized frogs between 220 and 320 (n = 18) fibres. By electron microscopy muscle fibres undergoing degeneration or phagocytosis can be seen (3 of 20 muscle fibres present in a single ultrathin cross-section). On the other hand several profiles contained within one common basal lamina sheath are present in 14 of 20 fibres, indicating satellite cell proliferation. In one preparation 40 months after denervation not a single muscle fibre or axon is present, suggesting that eventually, without nerve supply, muscle fibres entirely disappear. Upon spontaneous reinnervation or implantation of the hypoglossal nerve 16 months after denervation, synapses are formed with the remaining muscle fibres. When studied 3.5-24 months after nerve implantation muscles innervated by few axons only (less than 10, 10-20 axons) contain a low number of muscle fibres (mean 44 +/- 41 SD, n = 6), while all muscles with a larger number of axons have more than 150 muscle fibres (n = 6). This indicates that unless large numbers of axons regenerate and/or when reinnervation is delayed muscle fibre loss continues to occur. The presence in one muscle of motor axons but only six muscle fibres 24 months after nerve implantation indicates that muscle fibre loss cannot be reversed, or recovery is extremely slow. This observation is interpreted as evidence for the exhaustibility of the satellite cell pool.

Action Potentials↗
PubMed1988

Prolonged nerve stimulation causes changes in transmitter release at the frog neuromuscular junction.

1. Synaptic transmission in the two cutaneus pectoris muscles of frog was compared after prolonged unilateral nerve stem stimulation in vivo via surface electrodes. 2. In Mg2+-blocked preparations at 2 Hz stimulation the mean number of quanta released per impulse (m) was significantly lower in the stimulated muscles. On average, m was reduced to 53% (range 31-74%) of the values in control muscles. 3. Similarly, in curare-blocked preparations end-plate potential (EPP) amplitudes in the stimulated muscles were reduced to 30-92% (average 63%) of the control values, while no differences in muscle fibre diameter and resting potential were detectable. 4. In most muscles plateau values after tetanic stimulation at 40 Hz for 2 s were also smaller in the stimulated muscles. Compared to the first EPP in the train, however, plateau values were less depressed in stimulated than in unstimulated muscles. Also facilitation, i.e. the amplitude ratio of the largest versus the first EPP was more pronounced in stimulated muscles. 5. No effects of stimulation were noticed in four winter frogs, in which transmitter release is depressed due to seasonal factors. 6. It is concluded that prolonged nerve stimulation can cause under certain conditions profound depression of transmitter release with changes in facilitation and depression.

Action Potentials↗
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↗
PubMed1986

Sprouting and nerve retraction in frog neuromuscular junction during ontogenesis and environmental changes.

Based on recent evidence for a physiological remodeling of neuromuscular contacts (Wernig et al.), a morphometric study was performed on axon- and cholinesterase-stained cutaneous pectoris muscle of frog. The aim of this investigation was to separate changes due to aging, growth, and environmental conditions. Within a single muscle, fiber diameters, synaptic lengths, number of intraterminal branches, and lengths of abandoned gutters differ considerably (with coefficients of variation from 40 to 56%). On the other hand, these parameters are correlated and correlations hold when muscle fibers grow during ontogenesis: large muscle fibers bear larger and more complex junctions than small fibers. Obviously there exist growth regulating interactions between muscle fiber and the presynaptic nerve. To dissociate between age- and growth-related changes muscle fibers of equal diameters in frogs of different age are compared. With increase in age there is an additional increase in abandoned gutters, synaptic length, and complexity independent of muscle fiber growth. Possibly, abandoned gutters accumulate with time and synaptic length increases with age as the net outcome of continual synapse remodeling. When freshly caught frogs (October) were compared with frogs kept under laboratory conditions for a period of 16 weeks (which in addition included a change in season) the number of sprouts in a junction increased by about 2, the average length of presynaptic nerve terminals with small circumscribed contacts increased by 30-150 microns, and abandoned gutters tended to be shorter on fibers with large junctions. The hypothesis is discussed that remodeling is "inherent" to nerve terminals whereby sprouting is counterbalanced and reversed by nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1985

The distribution of acetylcholine receptors in the normal and denervated neuromuscular junction of the frog.

A combined light and electron microscopic investigation was performed to study the distribution and fate of clusters of horseradish peroxidase (HRP)-labelled or rhodamine-labelled alpha-bungarotoxin binding sites in normal and denervated cutaneous pectoris muscles of the frog. After staining for axon and cholinesterase (ChE) it appears that, in normal muscles, binding sites for rhodamine alpha-bungarotoxin are strictly confined to those parts of the synaptic gutter occupied by the nerve terminal. Binding sites are missing in axon-abandoned gutters or gutters occupied only by the Schwann cell. Similarly, in partially occupied gutters, HRP-toxin binding sites are confined to the parts of the muscle fibre membrane apposed to the nerve; they are missing at axon-free lateral parts at which secondary clefts and ChE are present. These observations suggest that junctional acetylcholine (ACh) receptor clusters are strictly controlled by the nerve. Thirty-five days after denervation, receptor density was apparently reduced in some parts of the gutters while other parts of the same gutters showed high receptor density. In addition, the length of gutter totally devoid of receptor clusters increased from an average fraction of 9% in control muscles to 14% in denervated muscles. Loss of receptors occurred both at Schwann cell-free and at Schwann cell-occupied gutters. In muscles denervated for 500-750 days, no toxin binding sites could be detected in the junctional membrane, whereas ChE was still present. Schwann cells had apparently abandoned some gutters but were present at others. Upon arrival of spontaneously reinnervating axons, muscle fibres accumulate ACh receptor clusters at the junctional membrane. Patches intensely labelled with alpha-bungarotoxin and associated with ChE reaction product were found near former junctions in long-term denervated muscles. It is concluded that after long-term denervation the muscle fibre cannot maintain junctional ACh receptor clusters by itself. In normally innervated muscles, receptor clusters are actively maintained by nerve-borne factors near the transmitter release sites.

Animals↗
PubMed1984

Persistence of nerve sprouting with features of synapse remodelling in soleus muscles of adult mice.

An increase in the number of nerve branches of the unmyelinated axon terminals with increasing age was observed in normal adult mouse motor endplates. In addition, ultrastructural investigation revealed signs of nerve retraction. A combined light and electron microscopic investigation was performed on zinc-iodine-osmium stained endplates in soleus muscles. The number of branch points in a synapse, endplate length and muscle fiber diameter were evaluated in "young adult" (3 months) and adult (6 and 11 months) mice. For all 3 parameters, 3-month-old animals had the lowest values. Eleven-month-old animals had more branch points and larger endplate lengths than 6-month-old animals while there was no significant difference in fiber diameters. Branch point numbers and endplate length were correlated in each muscle while fiber diameters did not correlate with any of the other parameters. The ultrastructure of 15 thin nerve branches--likely candidates for new branches--was investigated in serial section and in 14 of them synaptic contacts were found. Near such contacts, empty gutters, possibly abandoned former synaptic sites, were present in several cases. It is concluded that there is continual nerve sprouting in synapses of adult mice and that sprouts form synaptic contacts. The possible signs of nerve retraction observed indicate that, as in the frog, synaptic contacts in mouse muscles undergo some continual remodeling.

Aging↗