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PubMed1982

The effect of denervation of the cyclic nucleotides levels of the vas deferens.

We measured the cyclic nucleotides in levels of the rat vas deferens surgically denervated in order to investigate the relationship between denervation supersensitivity and cyclic nucleotides. Two days after denervation, cyclic AMP slightly decreased to 90.4% of control and cyclic GMP also decreased but not significantly. So it is assumed that almost all of the cyclic nucleotides are not neurogenic but myogenic. When the rat vas deferens was incubated with l-norepinephrine 10(-4) for 3 min, the cyclic GMP level in the vas deferens denervated for seven d was significantly higher than that in the intact specimen, and the cyclic AMP level in the intact one was almost the same as in the denervated preparation. Denervation produced leftward shift of the dose response curve in cyclic GMP level to l-norepinephrine. After incubation with acetylcholine (10(-4)M), however, cyclic GMP and cyclic AMP levels in the denervated vas deferens were almost the same as in the intact one. Therefore, it is suggested that cyclic nucleotides don't relate to the induction of nonspecific supersensitivity by denervation in the rat vas deferens.

Acetylcholine↗
PubMed1985

Renal denervation inhibits hypothalamo-sympathetic nerve system in normotensive and hypertensive rats.

The role of the renal nerve in influencing the hypothalamo-sympathetic nerve system to regulate the cardiovascular system was studied in normotensive Wistar and spontaneously hypertensive rats (SHR). Renal denervation attenuated pressor and sympathetic nerve responses to electrical stimulation of the hypothalamus without lowering the basal blood pressure at 48 hours after denervated operation. These findings suggest that renal denervation could inhibit the hypothalamo-sympathetic nerve system in normotensive rats. The development of hypertension in SHR was completely inhibited by renal denervation during 2 weeks of observation (from 7 to 9 weeks of age) without increasing water intake and urine volume. Pressor responses to intravenous injection of norepinephrine were not affected by renal denervation. The results show that the antihypertensive effect of renal denervation was not due to the changing of vascular reactivity. Pressor and sympathetic nerve responses to hypothalamic stimulation were strongly diminished in renal denervated rats. These results suggest that renal denervation strongly inhibited they hypothalamo-sympathetic nerve system. It is also suggested that the renal afferent nerve may facilitate the hypothalamo-sympathetic nerve system in regulating blood pressure and that this facilitation may contribute to the development of hypertension in SHR.

Animals↗
PubMed2005

Effect of salbutamol on innervated and denervated rat soleus muscle.

The objective of the present investigation was to perform a 14-day time-course study of treatment with salbutamol, a beta2 adrenoceptor agonist, on rat soleus muscle in order to assess fiber type selectivity in the hypertrophic response and fiber type composition. Male Wistar rats were divided into four groups: control (N = 10), treated with salbutamol (N = 30), denervated (N = 30), and treated with salbutamol after denervation (N = 30). Salbutamol was injected intraperitoneally in the rats of the 2nd and 4th groups at a concentration of 0.3 mg/kg twice a day for 2 weeks. The muscles were denervated using the crush method with pean. The animals were sacrificed 3, 6, 9, 12, and 14 days after treatment. Frozen cross-sections of soleus muscle were stained for myosin ATPase, pH 9.4. Cross-sectional area and percent of muscle fibers were analyzed morphometrically by computerized image analysis. Treatment with salbutamol induced hypertrophy of all fiber types and a higher percentage of type II fibers (21%) in the healthy rat soleus muscle. Denervation caused marked atrophy of all fibers and conversion from type I to type II muscle fibers. Denervated muscles treated with salbutamol showed a significantly larger cross-sectional area of type I muscle fibers, 28.2% compared to the denervated untreated muscle. Moreover, the number of type I fibers was increased. These results indicate that administration of salbutamol is able to induce changes in cross-sectional area and fiber type distribution in the early phase of treatment. Since denervation-induced atrophy and conversion from type I to type II fibers were improved by salbutamol treatment we propose that salbutamol, like other beta2 adrenoceptor agonists, may have a therapeutic potential in improving the condition of skeletal muscle after denervation.

Adrenergic beta-Agonists↗
PubMed2000

Changes of renal function and blood pressure after nitric oxide synthase inhibition in renal-denervated conscious rats.

Conscious male Wistar rats with implanted catheters in femoral artery for blood pressure registration, femoral vein for drug infusion and bladder for urine collection were used. Nitric oxide synthase inhibition (NOSI) was performed by intravenous administration of 10 mg/kg b.w. N(omega)-nitro-L-arginine methyl ester (L-NAME) before and one week after bilateral renal denervation. Renal denervation led to a decrease of urine osmolality (p<0.05). NOSI decreased heart rate (p<0.001) and increased systolic, mean and diastolic artery pressure both in the intact and the renal-denervated rats (p<0.001). The P(MF)/P(HF) ratio in the heart rate spectrum, considered a criterion for the sympathovagal balance decreased after NOSI in intact and in renal-denervated rats (p<0.001) indicating a reduction in the sympathetic tone. The baroreflex sensitivity after NOSI increased both in conscious rats with intact renal nerves and in rats with bilateral renal denervation. In intact rats NOSI increased urine flow rate by 48.7% (p<0.05), sodium excretion by 339.7% (p<0.01) and chloride excretion by 272.1% (p<0.01). In contrast to the intact rats, NOSI in the renal denervated rats decreased their urine flow rate by 35.5% (p<0.05) and did not alter sodium and chloride excretion. So, chronic renal denervation inversed the diuretic and clearly attenuated the natriuretic and chloruretic response to acute NOSI without inhibiting the rise in blood pressure. Therefore, the increased urine flow as well as the sodium and chloride excretion observed after NOSI are not exclusively the result of a pressure diuresis but are somewhat dependent on the renal sympathetic nerve activity. Renal denervation did not change the pattern of sympathovagal balance and baroreflex sensitivity modified by NO-synthase inhibition.

Animals↗
PubMed2003

Changes in protein levels of elongation factors, eEF1A-1 and eEF1A-2/S1, in long-term denervated rat muscle.

PURPOSE: This study was designed to determine whether the quantitative relationship between the levels of the eEF1A-1(developmental) and eEF1A-2/S1 (adult) isoforms of peptide elongation factor remains stable after denervation of skeletal muscle or whether in response to denervation the relative amount of the developmental form would increase. In normal postnatal rat muscle, eEF1A-2/S1 is the dominant form represented, and levels of eEF1A-1 are extremely low. METHODS: One hind limb in young adult rats was permanently denervated. Denervated and corresponding contralateral control muscles were removed for biochemical and morphological analysis from 2 days to 25 months after denervation. RESULTS: By one month after denervation, relative levels of eEF1A-1 rose dramatically in relation to those of eEF1A-2/S1, and they remained high throughout the remainder of the 25-month denervation period. Ultrastructural analysis showed a complex mix of muscle fiber atrophy, dying muscle nuclei and muscle fibers, and newly forming muscle fibers in the same tissue. CONCLUSIONS: As during muscle regeneration, levels of the developmental eEF1A-1 isoform of peptide elongation factor greatly increased relative to those of the adult eEF1A-2/S1 adult isoform following denervation in rat muscles. However, in contrast to regeneration, the elevated level of eEF1A-1 did not return to the basal minimal level. Since switching from eEF1A-1 to eEF1A-2/S1 is an indicator that terminal differentiated is completed, the failure of eEF1A-1 to return to basal level may be indicative of the persistence of an unstable tissue environment that includes muscle fiber atrophy, degeneration and neomyogenesis. The specific cellular basis for the increase in eEF1A-1 could not be determined from this study.

Animals↗
PubMed1990

[Effects of denervation of the masseter nerve and bite raising on the masseter muscle of developing rats].

The effects of masseteric denervation and bite raising on muscle fiber type differentiation were examined in the masseteric muscle of developing rats by histological and histochemical studies. Three-week-old Wistar rats had of their masseteric nerve at right side dissected, and a part of them were bite raised at anterior region one week after denervation for three weeks. The unoperated side and number of sham animals served as control. The animals were killed 3, 7, 10, 14, 21, 28, 35, 49 days later and then their masseter muscles were removed wholly and weighed them. After freezing of superficial and deep masseter muscles serial sections were made and HE staining carried out, ATPase staining and NADH-TR staining. On the photographs of the HE stained specimens, I measured the diameter of the muscle fibers. Gross findings on the denervated group, revealed the lower incisors shifted to unoperated side and on with the bite raising group, it shifted to the operated side. In denervated animals, the wet weight of the masseter muscle had decreased significantly. The masseteric muscle fibers in three-old-week control rats were undifferentiated on ATPase staining, but it became well differentiated on and after four-old-week. The superficial masseter of control mainly composed of type 2B fibers. In the deep masseter, about 10% type 1 and 2C fibers were found in limited area around the muscle spindles, and surrounded with type 2A and 2B fibers. In superficial masseter muscle of the denervated group, the percentage of type 2A fibers increased, and that of type 2B fibers decreased. The type 2C fibers were found from the 21st days after denervation. In deep masseter muscles, the percentage of type 1 and 2A fibers decreased, and that of type 2B and 2C fibers increased. In the denervated bite raising group, the composition of the muscle fiber type approached the control group. These results as above suggested, masseteric denervation causes degeneration of muscle fiber composition, and the possibility that early preventive treatment like bite raising may recover the muscle fiber composition normally.

Animals↗
PubMed1979

Denervation-induced changes in alpha and beta adrenergic receptors of the rat submandibular gland.

Denervation resulted in a marked increase in the beta adrenergic response and isoproterenol-stimulated cyclic adenosine 3':5'-monophosphate accumulation of dispersed cells prepared from a rat submandibular gland. This increase in beta adrenergic response was paralleled by an increase in the density of beta adrenergic receptors in membranes prepared from these glands. Denervation also produced a moderate increase in alpha adrenergic receptor density in membranes prepared from whole glands. However, the alpha adrenergic response in cells, epinephrine-induced release of potassium, appeared unaltered by denervation. Furthermore, membranes prepared from denervated dispersed cells did not show the increase in alpha adrenergic receptor density seen in membranes from an intact denervated gland. These data demonstrate that removal of noradrenergic nerve terminals affects alpha and beta adrenergic receptors differently. While it is clear that beta adrenergic membrane receptors participate in denervation-induced supersensitivity, the changes in alpha adrenergic membrane receptors are more complex and may not contribute to the supersensitivity seen after denervation. On the basis of competitive binding studies, the adrenergic receptors in membranes from intact submandibular glands were subclassified as beta-1 and alpha-2. Denervation did not alter the binding characteristics of the alpha-2 receptors in this gland, demonstrating that alpha-2 adrenergic membrane receptors can be postsynaptic in this adrenergically innervated tissue.

Animals↗
PubMed1987

Effects of noradrenergic denervation on alpha-1 adrenoceptors and receptor-stimulated contraction of chick expansor secundariorum muscle.

Alpha-1 adrenoceptors were identified in the chick expansor secundariorum (ESM) smooth muscle by ligand binding (using [3H]prazosin) and organ bath techniques. We examined the effects of both reversible (6-hydroxydopamine-induced) and irreversible (surgical) noradrenergic denervation on alpha-1 adrenoceptors in the ESM. We also measured, in vitro, muscle contraction stimulated by the alpha-1 adrenoceptor agonist methoxamine and by 5-hydroxytryptamine. After both surgical and chemical denervation there were decreases in the number of [3H] prazosin binding sites in the ESM. After reversible denervation the decrease in receptor number persisted during a period in which there was extensive reinnervation of the muscle. At a time (7 days after injection) when the ESM was partially reinnervated the maximum methoxamine-stimulated response, but not that of 5-hydroxytryptamine, was reduced. After surgical (but not chemical) denervation there were increases in both protein content and wet weight of the muscle. However, at 7 days after denervation, these effects alone could not account for the observed decrease in receptor number. A small increase in sensitivity (1.4-fold) to methoxamine and a much larger increase in sensitivity (4.5-fold) to 5-hydroxytryptamine developed after surgical denervation but there appeared to be nonspecific decreases in maximum responses to the agonists. It is concluded that both surgical and chemical denervation produced a decrease in alpha-1 adrenoceptor number in the ESM; this may have contributed to the decrease in maximum contractile response. After surgical denervation a nonspecific supersensitivity developed in the ESM; it may be that a nonspecific contribution to methoxamine-stimulated responses was less apparent due to the loss of alpha-1 adrenoceptors.

Animals↗
PubMed1988

Excretory function after renal denervation and administration of diuretics to unanesthetized dogs.

Diuretics were administered intravenously to unanesthetized dogs with exteriorized ureters for separate urine collection from both kidneys: furosemide (0.2 mg/kg), ethacrynic acid (0.22 mg/kg), acetazolamide (3.0 mg/kg), amiloride (1.0 mg/kg b.w.). Diuresis, urine and plasma osmolality, excretion, clearances and excretion fractions of sodium, potassium, chloride and magnesium were determined. After left-side kidney denervation not later than 50 days after operation, the above mentioned diuretics were administered to the same animals. The responses of the denervated and intact kidneys were compared. During some of the experiments after furosemide administration isotonic solution of sodium chloride in a volume, adequate to the volume of the collected urine, was infused. Furosemide or ethacrynic acid administration leads to a higher increase of both diuresis and chloride excretion from denervated kidney as compared to the intact one. After ethacrynic acid administration magnesium excretion from the denervated kidney was registered to be higher than that from the intact one. After chronic renal denervation of unanesthetized dogs, chloride and magnesium reabsorption in the ascending limb of Henle's loop was greater in the denervated than in the intact kidney. Amiloride suppression of potassium secretion in the distal part of the nephron did not lead to differences between the denervated and intact kidneys. The decreased volume of extracellular liquid, resulting from diuretic action, did not change the response of the denervated kidney to furosemide or to ethacrynic acid.

Acetazolamide↗
PubMed1987

Transient and chronic neonatal denervation of murine muscle: a procedure to modify the phenotypic expression of muscular dystrophy.

The extensor digitorum longus muscles of 14-d-old normal (129 ReJ ++) and dystrophic (129 ReJ dy/dy) mice were denervated by cutting the sciatic nerve. One denervation protocol was designed to inhibit reinnervation of the shank muscles, the other to promote reinnervation. Chronically denervated muscles (muscles that remained denervated for 100 d after nerve section) exhibited marked atrophy, but the number of myofibers in these muscles (1066 +/- 46 and 931 +/- 62 for the denervated normal and dystrophic muscles, respectively) was similar to the number of myofibers found in age-matched, unoperated normal muscles [922 +/- 28 (Ontell et al., 1984)] and was significantly greater than the number of myofibers found in age-matched dystrophic muscles [547 +/- 45 (Ontell et al., 1984)]. Similar effects on myofiber number were obtained when denervated muscles were allowed to reinnervate. Reinnervation of both normal and dystrophic muscles mitigated the marked atrophy that characterized chronically denervated muscles. The dystrophic reinnervated muscles appeared "healthier" than age-matched, unoperated dystrophic muscles, having 70% more myofibers, less myofiber diameter variability, substantially less connective tissue infiltration, and a greater amount of contractile tissue at their widest girths. The present study demonstrated that it is possible to alter the phenotypic expression of the histopathological changes associated with murine dystrophy, in dystrophic myofibers that are formed during fetal development, by subjecting the muscle to neonatal denervation.

Animals↗
PubMed1985

Study of sodium and potassium excretion after renal denervation and cholinergic stimulation of the lateral hypothalamic area of the rat.

Studies were undertaken to characterize the renal responses to acute unilateral renal denervation and chronic bilateral denervated kidneys after cholinergic stimulation of the anterior part of the lateral hypothalamus. Denervation was produced in anesthetized and conscious nondiuretic rats by application of phenol to the renal artery. Studies were also performed in sham denervated rats. Whole kidney function in anesthetized animals showed a significant increase of fractional sodium excretion (0.7 +/- 0.1 to 1.7 +/- 0.4%, P less than 0.01) both in the denervated and in the innervated kidney (0.09 +/- 0.02 to 1.1 +/- 0.2%, P less than 0.005) after carbachol injection into the LHA, whereas the percentage of filtered potassium excreted increased only in the innervated kidney (11.4 +/- 1.3 to 16.3 +/- 1.1%, P less than 0.01). Similarly, in conscious rats, fractional sodium excretion increased after cholinergic stimulation in animals having denervated kidneys (2.1 +/- 0.1 vs 3.6 +/- 0.2%, P less than 0.005). Fractional potassium excretion also increased both in rats with sham-denervated and denervated kidney. There was an acute elevation in mean arterial blood pressure and glomerular filtration rate (GFR) during the first 20-min after carbachol injection. Sodium excretion was statistically significant during the three 20-min collections of the experimental period. This suggests that the natriuresis is not associated with increased arterial pressure, GFR or renal plasma flow. Our results indicate that natriuresis occurs even in the absence of the renal nerves.

Animals↗
PubMedDate not supplied

Combined effects of tenotomy and denervation on the dynamic properties of soleus muscle of the rat.

Isometric contraction time (CT), half relaxation time (1/2 RT), tetanus fusion frequency (TFF) and tetanus: twitch ratio (T : t ratio) were measured in the denervated (D) and tenotomized-denervated (TD) Soleus muscle of the rat. In D muscle there was an apparent speeding effect at the 2nd day after denervation, with a significant decrease of CT, which was followed by the usual slowing process of denervated muscle. In TD muscle, denervation was performed a week after tenotomy. Tenotomy "per se" was ineffective in modifying dynamic properties of muscle, but it accentuated the early shortening of CT caused by denervation, while reducing and delaying the subsequent slowing process. The results are discussed in the light of the hypothesis that muscle disuse has a speeding effect which counteracts the slowing effect of denervation, and/or that tenotomy modifies the effects of denervation by changing the pattern of fibrillation development.

Animals↗
PubMed1978

Denervation-induced changes in electrophysiologic parameters of the smooth muscle of the guinea-pig and rat was deferens.

In order to further elucidate the mechanisms by which postganglionic denervation causes changes in the dose-response curves obtained in smooth muscle, microelectrodes have been used to investigate cellular changes in the denervated guinea-pig and rat vas deferens. In the guinea-pig vas deferens, chronic denervation produced a partial depolarization (mean change of 8.5 mV) without any change in threshold for the action potential. In the rat vas deferens there was no change in resting potential but the threshold membrane potential because more negative (6.5 mV). Thus, in both species, but apparently by different mechanisms, the resting and threshold membrane potentials are brought closer together by denervation. Such an effect would clearly contribute to the well documented increase in sensitivity to depolarizing agonists which is produced by chronic denervation. In both species, denervation increased the space constant of the smooth muscle, an indication of increased electrical coupling among the cells. This observation is consistent with morphologic evidence of improved coupling induced by denervation and presented previously from this laboratory. The improved coupling appears to be associated with the increased maximum response of the denervated vasa deferentia of both species. These results are discussed in references to known similarities and differences in electrophysiologic characteristics between normal guinea-pig and rat vasa deferentia.

Action Potentials↗
PubMed1984

Alpha-1 adrenoceptors mediate secretory responses to norepinephrine in innervated and denervated rat submaxillary glands.

The alpha adrenoceptor that mediates the secretory responses to norepinephrine in submaxillary glands was characterized. All three alpha antagonists employed produced in innervated glands parallel displacements of the dose-response curves to norepinephrine, prazosin being 30 and 100 times more potent than phentolamine and yohimbine, respectively. Chronic sympathetic denervation produced supersensitivity to norepinephrine. Under these conditions prazosin also was more potent than yohimbine but the shifts of the dose-response curves to norepinephrine were nonparallel. Potentiation of norepinephrine by cocaine did not modify the effects of prazosin in innervated glands. The nonparallel displacements observed in denervated glands were related to the development of postjunctional supersensitivity of the beta adrenoceptor-mediated responses because after administration of propranolol the displacements produced by prazosin were parallel. Responses to methoxamine were not potentiated by denervation and were competitively antagonized by prazosin in both innervated and denervated glands. Specific [3H]clonidine binding to membranes of submaxillary glands showed at least two independent sites with a KD1 of 0.37 nM and a KD2 of 65 nM. The number of sites of each component was doubled after chronic sympathetic denervation. Binding of [3H]prazosin (KD, 0.43 nM; maximum binding sites, 78.5 fmol/mg of protein) was not affected by denervation. The present findings show that sialagogue responses to sympathomimetic agents are mediated by alpha-1 adrenoceptor activation in both innervated and denervated submaxillary glands. Chronic sympathetic denervation does not produce postjunctional supersensitivity of the alpha-1-mediated responses and the supersensitivity of the beta-mediated responses interferes with determinations of dose-response curves to the sympathetic neurotransmitter.

Animals↗
PubMed1984

Insulin action in denervated rat hemidiaphragms. Decreased hormonal stimulation of glycogen synthesis involves both glycogen synthase and glucose transport.

Rat hemidiaphragms were denervated in vivo and then incubated in vitro to assess the ability of insulin to stimulate glycogen synthesis. Denervation for 1 day resulted in 50% decreases in the stimulation by insulin of [U-14C]glucose incorporation into glycogen, and in both the basal and the insulin-stimulated activity ratios (activity minus glucose-6-P/activity plus glucose-6-P) of glycogen synthase; however, the stimulation of 2-deoxyglucose uptake by insulin was not affected by 1 day of denervation. The hormonal stimulation of [U-14C]glucose into glycogen was decreased by 90% after 3 days of denervation. At this time, the stimulation of 2-deoxyglucose uptake by insulin was also reduced and the synthase activity ratios remained depressed. Consistent with its reduced effect on glucose transport, the hormone did not increase glucose-6-P in the 3-day denervated muscles. Furthermore, the Ka for activation of glycogen synthase by glucose-6-P was higher in denervated muscles, and denervation abolished the effect of insulin on decreasing the Ka. The results presented demonstrate that denervation rapidly reduces the extent to which glycogen synthase can be activated by insulin, and has a later effect on decreasing the stimulation of glucose transport. These two effects act synergistically to markedly decrease the hormonal stimulation of glycogen synthesis.

Animals↗
PubMed1983

Acetylcholine sensitivity and fibrillation potentials in electrically stimulated crush-denervated rat skeletal muscle.

Juxtamuscular electrodes were implanted unilaterally in six groups of adult female Wistar rats to evaluate the effect of chronic electrical stimulation (ES) during denervation and reinnervation of the rat soleus muscle. Two weeks later, the animals underwent bilateral crush-denervation of the sciatic nerve at the sciatic notch. Six additional groups served as normal controls. The soleus muscles in the crush denervated and control groups were stimulated unilaterally with a 4mA, 4msec duration current given at 10Hz continuously 8 hours each day for 5, 10, 15, 20, 25 or 30 days. At the end of each period, the soleus muscles were evaluated for the muscle weights, acetylcholine (ACh) sensitivity and fibrillation potentials (FPs). The normal muscles were unaffected by the stimulation. The denervated-stimulated soleus muscles were heavier at 10 days (p less than 0.05) and had fewer FPs after 5 to 15 days (p less than 0.01) of electrical stimulation than their matched denervated controls. The ACh sensitivity throughout the experimental period and the fibrillatory activity from 20 to 30 days post-crush were similar in the denervated and the denervated-stimulated muscles. In conclusion, ES reduced the degree of atrophy and the number of fibrillations of the soleus muscle in the denervation stage. However, it neither enhanced nor impaired the reinnervation of muscle.

Acetylcholine↗
PubMed1980

Increased activities of acid protease and acid phosphatase in denervated forelimb regenerates of the adult newt, Notophthalmus viridescens.

Early bud and palette limb regenerates of the adult newt, Notophthalmus viridescens, were compared with respect to the effect of denervation on the activities of some of their hydrolases in order to determine if these enzymes contribute to the atrophy of denervated regenerates. Results show that denervation increased total activities of acid protease and acid phosphatase by 77-89% and 41-45% respectively at both stages examined. Both membrane-bound and soluble enzymatic forms contributed to the observed increase in the total activity of each hydrolase. Furthermore, the actual levels of each enzyme attained at the two stages following denervation were quite similar to each other. Since each hydrolase responded to denervation in a similar way at both stages examined, it was concluded that resorption of denervated limb regenerates is not primarily due to the increased activity of hydrolases. Denervated early bud regenerates, which are almost completely resorbed following nerve withdrawal, would be expected to show greater levels of hydrolytic activity than denervated palette regenerates, which exhibit only a partial resorption following the same operation.

Acid Phosphatase↗
PubMed1997

DNA-fragmentation and expression of apoptosis-related proteins in experimentally denervated and reinnervated rat facial muscle.

Muscle fibres may undergo apoptotic cell death in several neuromuscular disorders such as denervated muscle fibres in spinal muscular atrophies. We investigated DNA-fragmentation (in situ by the TUNEL-method) and expression of apoptosis-associated proteins in experimentally denervated and reinnervated rat facial muscle up to 24 weeks after surgery to evaluate the rate and time lapse of apoptotic muscle fibre loss. While denervated muscle displayed constantly high rates of DNA-fragmentation, denervated and immediately reinnervated muscle showed a distinct decrease of primarily elevated DNA-cleavage, finally resembling rates of normal controls. Denervated muscle fibres revealed strong immunoreactivity of the anti-apoptotic proteins bcl-2 and bcl-xL, and the pro-apoptotic factor bax. In reinnervated muscle fibres, only bcl-2 was constantly upregulated while bcl-xL and bax diminished after the 7th week. The present findings indicate that denervation may prompt muscle fibres to activate an intrinsic 'suicide' programme to undergo apoptosis. High levels of bcl-2 after denervation may sustain cell survival until reinnervation, e.g. after accidental nerve damage or in neurodegenerative disorders. Furthermore, increasing levels of bcl-2 are able to neutralize high apoptosis-promoting bax levels. Interventions modifying DNA-fragmentation and the expression of apoptosis-related proteins may lead to new therapeutic concepts in denervating disorders of muscle in the absence of other primary therapies.

Animals↗