Reduced Muscle Weight Research Articles

Sex-dependent effects of maternal undernutrition on growth performance, carcass characteristics and meat quality of lambs

The present study evaluated the sex-specific effects of maternal undernutrition induced by a lower natural pasture allowance (between gestation days 30 and 143) on growth performance, carcass and meat quality of lambs. Thirty-three single-bearing multiparous Corriedale ewes were randomly assigned to two natural pasture allowances: a) Sixteen HPA (high pasture allowance) ewes (eight carrying male and eight carrying female lambs) grazed on 14–20 kg of dry matter (DM)/100 kg of body weight (BW)/day; and b) Seventeen LPA (low pasture allowance) ewes (seven carrying male and ten carrying female lambs) grazed on 6–10 kg of DM/100 kg of BW/day. From gestation day 100 ewes were supplemented with rice bran. From gestation day 143 until weaning all animals grazed on natural pasture with unlimited availability and continued to be supplemented. After weaning lambs were individually ad libitum fed with a mixed diet (alfalfa hay and commercial mixed ration) until slaughtering at 200 days old. High pasture allowance ewes showed greater mean gestational BW (P ˂ 0.01), with differences between groups from day 55 on. Body weight differences between HPA and LPA ewes carrying female fetuses appeared earlier and were more profound (P ˂ 0.05) than those detected between ewes carrying male fetuses. Maternal undernutrition affected male (P = 0.05, sex-by-age-by-treatment and P = 0.01, sex-by-treatment interactions for lactation and fattening periods, respectively) but not female lamb growth. Carcass conformation and meat yield were affected by maternal undernutrition mostly in a sex-dependent manner. Male LPA lambs showed reduced area (P = 0.03, sex-by-treatment interaction) and tended to show reduced perimeter (P = 0.07, sex-by-treatment interaction) of the Longissimus muscle. Male LPA lambs showed narrower (P ˂ 0.01, sex-by-treatment interaction) and tended to show less compact carcasses (P = 0.09, sex-by-treatment interaction) and reduced buttock perimeters (P = 0.08, sex-by-treatment interaction). Sex-dependent muscle weight reduction was found for muscles Gluteobiceps, Supraspinatus and Semitendinosus (P = 0.02, sex-by-treatment interaction), with males but not females being affected. Maternal undernutrition affected meat quality in a sex-dependent manner, generally increasing meat lightness in most muscles from females, but not males. In conclusion, a reduced forage allowance of ewes from gestation day 30 until partum affected growth performance, carcass and meat quality of lambs mostly in a sex-dependent manner. Generally, males born to undernourished ewes grew more slowly and showed poorer quality carcasses and reduced meat yields, while females born to undernourished ewes generally showed brighter meat.

Urotensin II Induces Mice Skeletal Muscle Atrophy Associated with Enhanced Autophagy and Inhibited Irisin Precursor (Fibronectin Type III Domain Containing 5) Expression in Chronic Renal Failure

Background/Aims: Skeletal muscle atrophy is one of the main manifestations of protein energy wasting. We hypothesized that urotensin II (UII) can lead to skeletal muscle atrophy through upregulating autophagy and affecting Irisin precursor fibronectin type III domain containing 5 (FNDC5) expressions. Methods: Three animal models (the sham operation, wild-type C57BL/6 mice with 5/6 nephrectomy, UII receptor (UT) gene knockout (UTKO) mice with 5/6 nephrectomy) were designed. Skeletal muscle weight, cross-sectional area (CSA) along with UII, FNDC5, LC3, and p62 expression were investigated. C2C12 cells were differentiated for up to 4 days into myotubes. These cells were then exposed to different UII concentrations (10^–5 to 10^–7 M) for 6–12 h and analyzed for the expressions of autophagic markers. These cells were also exposed to the same predetermined UII concentrations for 48–72 h and analyzed for the FNDC5 expression. Myotube diameter was measured. Results: Upregulation of UII expression in skeletal muscle tissue was accompanied by reduced muscle weight and skeletal muscle CSA in the 2 posterior limbs, upregulated autophagy markers expression, and downregulated FNDC5 expression in 5/6 nephrectomy mice. The decrease of skeletal muscle weight, skeletal muscle CSA, downregulation of FNDC5 expression, and the upregulation of autophagy markers were inhibited in UTKO with 5/6 nephrectomy mice. Our in vitrostudy showed that UII could directly decrease myotube diameter, induce autophagy markers upregulation, and inhibit expression of FNDC5. When UII receptor gene was interfered by UT-specific siRNA, UII induced autophagy markers upregulation and FNDC5 downregulation were inhibited. Conclusion: We are the first to verify UII induces mice skeletal muscle atrophy associated with enhanced skeletal muscle autophagy and inhibited FNDC5 expression in chronic renal failure.

Botulinum toxin A-induced muscle paralysis stimulates Hdac4 and differential miRNA expression.

At sufficient dose, intramuscular injection of Botulinum toxin A causes muscle wasting that is physiologically consistent with surgical denervation and other types of neuromuscular dysfunction. The aim of this study was to clarify early molecular and micro-RNA alterations in skeletal muscle following Botulinum toxin A-induced muscle paralysis. Quadriceps were analyzed for changes in expression of micro- and messenger RNA and protein levels after a single injection of 0.4, 2 or 4U Botulinum toxin A (/100g body weight). After injection with 2.0U Botulinum toxin A, quadriceps exhibited significant reduction in muscle weight and increased levels of ubiquitin ligase proteins at 7, 14 and 28 days. Muscle miR-1 and miR-133a/b levels were decreased at these time points, whereas a dose-responsive increase in miR-206 expression at day 14 was observed. Expression of the miR-133a/b target genes RhoA, Tgfb1 and Ctfg, and the miR-1/206 target genes Igf-1 and Hdac4, were upregulated at 28 days after Botulinum toxin A injection. Increased levels of Hdac4 protein were observed after injection, consistent with anticipated expression changes in direct and indirect Hdac4 target genes, such as Myog. Our results suggest Botulinum toxin A-induced denervation of muscle shares molecular characteristics with surgical denervation and other types of neuromuscular dysfunction, and implicates miR-133/Tgf-β1/Ctfg and miR-1/Hdac4/Myog signaling during the resultant muscle atrophy.

Resistance training downregulates macrophages infiltration in the kidney of 5/6 nephrectomized rats

IntroductionChronic kidney disease (CKD) is considered a significant world health problem with elevated mortality rates. Patients with CKD are restricted to mild physical activity, present chronic inflammatory state and loss of muscle strength. Currently, the influence of resistance exercise (RE) on the progression of renal disease has not being fully elucidated. PurposeTo evaluate the effects of RE on the progression of CKD in a remnant kidney model (5/6Nx) in rats. MethodsEight-week-old Wistar rats were submitted to 5/6 nephrectomy and were divided into four groups: Sham sedentary (Sham SD); Sham RE (Sham RE); 5/6Nx SD and 5/6Nx RE. The animals were trained for 8 weeks in a vertical climbing ladder for 3 days per week, on non-consecutive days. ResultsAs expected, 5/6Nx SD group presented a markedly loss of renal function, increased plasma inflammatory cytokines and increased oxidative stress with a reduced activity of nitric oxide. The higher macrophage infiltration and fibrosis confirmed these conditions. RE attenuated systolic blood pressure and renal function decrease and also improved serum lipid parameters in 5/6 Nx animals. It was evident the increase of muscle strength and mass in the trained groups while the sedentary group showed reduced muscle weight and strength compared to Sham SD. ConclusionsRE implemented following 5/6Nx retard the progression of chronic kidney injury while simultaneously allowed the maintenance of skeletal muscle strength.

Micro-computed tomography for non-invasive evaluation of muscle atrophy in mouse models of disease.

Muscle wasting occurs during various chronic diseases and precedes death in humans as in mice. The evaluation of the degree of muscle atrophy in diseased mouse models is often overlooked since it requires the sacrifice of the animals for muscle examination or expensive instrumentation and highly qualified personnel, such as Magnetic Resonance Imaging (MRI). Very often behavioral tests for muscle strength evaluation are used as an outcome measurement in preclinical therapeutic trials. However, these tests are easy to perform serially, but not enough sensitive to detect early muscle changes during disease progression. Monitoring muscle loss in living animals could allow to perform more informative preclinical trials with a better evaluation of therapeutic benefit with respect to muscle wasting. We developed a non-invasive procedure based on micro-computed tomography (micro-CT) without contrast agents to monitor hind limb muscle wasting in mouse models of amyotrophic lateral sclerosis (ALS) and cancer cachexia: the transgenic SOD1G93A mouse and the colon adenocarcinoma C26-bearing mouse, respectively. We established the scanning procedure and the parameters to consider in the reconstructed images to calculate the Index of Muscle Mass (IMM). The coefficient of variance for the whole procedure was 2.2%. We performed longitudinally micro-CT scan of hind limbs in SOD1G93A mice at presymptomatic and symptomatic stages of the disease and calculated the IMM. We found that IMM in SOD1G93A mice was lower than age-matched controls even before symptom onset. We also detected a further decrease in IMM as disease progresses, most markedly just before disease onset. We performed the same analyses in the C26-based mouse model losing quickly body and muscle mass because of cancer cachexia. Overall, we found that the reduced muscle content detected by micro-CT mirrored the reduced muscle weight in both disease models. We developed a fast, precise and easy-to-conduct imaging procedure to monitor hind limb muscle mass, useful in therapeutic preclinical trials but also in proof-of-principle studies to identify the onset of muscle wasting. This method could be widely applied to other disease models characterized by muscle wasting, to assist drug development and search for early biomarkers of muscle atrophy. Moreover, reducing the number of mice needed for the experiments and being less distressing are in line with the 3R principle embodied in national and international directives for animal research.

Whole body ARHGAP21 reduction improves glucose homeostasis in high‐fat diet obese mice

GTPase activating proteins (GAPs) are ubiquitously expressed, and their role in cellular adhesion and membrane traffic processes have been well described. TBC1D1, which is a Rab-GAP, is necessary for adequate glucose uptake by muscle cells, whereas increased TCGAP, which is a Rho-GAP, decreases GLUT4 translocation, and consequently glucose uptake in adipocytes. Here, we assessed the possible involvement of ARHGAP21, a Rho-GAP protein, in glucose homeostasis. For this purpose, wild type mice and ARHGAP21 transgenic whole-body gene-deficiency mice (heterozygous mice, expressing approximately 50% of ARHGAP21) were fed either chow (Ctl and Het) or high-fat diet (Ctl-HFD and Het-HFD). Het-HFD mice showed a reduction in white fat storage, reflected in a lower body weight gain. These mice also displayed an improvement in insulin sensitivity and glucose tolerance, which likely contributed to reduced insulin secretion and pancreatic beta cell area. The reduction of body weight was also observed in Het mice and this phenomenon was associated with an increase in brown adipose tissue and reduced muscle weight, without alteration in glucose-insulin homeostasis. In conclusion, the whole body ARHGAP21 reduction improved glucose homeostasis and protected against diet-induced obesity specifically in Het-HFD mice. However, the mechanism by which ARHGAP21 leads to these outcomes requires further investigation.

Immunohistochemical Detection of Motor Endplates in the Long-Term Denervated Muscle.

We have demonstrated that the native motor zone (NMZ) within a muscle is an ideal target for performing nerve-muscle-endplate band grafting (NMEG) to restore motor function of a denervated muscle. This study was designed to determine spatiotemporal alterations of the myofibers, motor endplates (MEPs), and axons in the NMZ of long-term denervated muscles for exploring if NMEG-NMZ technique would have the potential for delayed reinnervation. Sternomastoid (SM) muscles of adult female Sprague-Dawley rats (n = 21) were experimentally denervated and denervation-induced changes in muscle weight, myofiber size, MEPs, and intramuscular nerve axons were evaluated histomorphometrically and immunohistochemically at the end of 3, 6, and 9 months after denervation. The values obtained from the ipsilateral normal side served as control. The denervated SM muscles exhibited a progressive reduction in muscle weight (38%, 31%, and 19% of the control) and fiber diameter (52%, 40%, and 28% of the control) for 3-, 6-, and 9-month denervation, respectively. The denervated MEPs were still detectable even 9 months after denervation. The mean number of the denervated MEPs was 79%, 65%, and 43% of the control in the 3-, 6-, and 9-month denervated SM, respectively. Degenerated axons in the denervated muscles became fragmented. Persistence of MEPs in the long-term denervated SM suggests that some surgeries targeting the MEPs such as NMEG-NMZ technique should be effective for delayed reinnervation. However, more work is needed to develop strategies for preservation of muscle mass and MEPs after denervation.

A low-protein diet exerts a beneficial effect on diabetic status and prevents diabetic nephropathy in Wistar fatty rats, an animal model of type 2 diabetes and obesity

BackgroundThe objective of this study is to investigate the effects of a low-protein diet (LPD) starting from a young age on diabetic status and renal injury in a rat model of type 2 diabetes and obesity.MethodsDiabetic male Wistar fatty (fa/fa) rats (WFRs) were fed a standard diet (23.84% protein) or an LPD (5.77% protein) for 24 weeks beginning at 6 weeks of age. We investigated the effects of the LPD on total body weight (BW); fat weight (FW); lower-limb muscle weight (MW); several measures of diabetic status, including fasting/random glucose levels, HOMA-IR and the IPITT; and renal injuries, including renal hypertrophy, albuminuria and histological changes. Additionally, autophagy and activation of mTORC1 were evaluated in the diabetic renal cortex. Furthermore, plasma FGF21 and high-molecular-weight (HMW) adiponectin levels, as well as UCP1 expression levels in brown adipose tissue (BAT), were evaluated.ResultsIncreases in BW and FW in WFRs were significantly reduced by the LPD, and the LPD resulted in a significant reduction of lower-limb MW in WFRs. The LPD suppressed the elevation of glucose levels in WFRs through improvement of insulin resistance. The LPD also elevated the plasma FGF21 and HMW adiponectin of WFRs, as well as UCP1 expression in the BAT of the animals. Renal hypertrophy, albuminuria, renal histological changes, and increased expression of p62 and phospho-S6 ribosomal protein (p-S6RP) were observed in WFRs compared with the values from WLRs. The LPD clearly prevented the diabetic kidneys from sustaining any damage.ConclusionsThe LPD prevented the progression of diabetic status; this effect may have been associated with the reduction of FW and the elevation of plasma FGF21 and HMW adiponectin, as well as UCP1 expression in BAT, resulting in suppression of diabetic nephropathy. However, MW was decreased in rats by the consumption of an LPD from a young age; therefore, further research is needed to resolve the nutritional issue of LPD on decreasing in MW.

Forkhead box O3 plays a role in skeletal muscle atrophy through expression of E3 ubiquitin ligases MuRF-1 and atrogin-1 in Cushing's syndrome.

Cushing's syndrome is caused by overproduction of the adrenocorticotropic hormone (ACTH), which stimulates the adrenal grand to make cortisol. Skeletal muscle wasting occurs in pathophysiological response to Cushing's syndrome. The forkhead box (FOX) protein family has been implicated as a key regulator of muscle loss under conditions such as diabetes and sepsis. However, the mechanistic role of the FOXO family in ACTH-induced muscle atrophy is not understood. We hypothesized that FOXO3a plays a role in muscle atrophy through expression of the E3 ubiquitin ligases, muscle RING finger protein-1 (MuRF-1), and atrogin-1 in Cushing's syndrome. For establishment of a Cushing's syndrome animal model, Sprague-Dawley rats were implanted with osmotic minipumps containing ACTH (40 ng·kg-1·day-1). ACTH infusion significantly reduced muscle weight. In ACTH-infused rats, MuRF-1, atrogin-1, and FOXO3a were upregulated and the FOXO3a promoter was targeted by the glucocorticoid receptor (GR). Transcriptional activity and expression of FOXO3a were significantly decreased by the GR antagonist RU486. Treatment with RU486 reduced MuRF-1 and atrogin-1 expression in accordance with reduced enrichment of FOXO3a and Pol II on the promoters. Knockdown of FOXO3a prevented dexamethasone-induced MuRF-1 and atrogin-1 expression. These results indicate that FOXO3a plays a role in muscle atrophy through expression of MuRF-1 and atrogin-1 in Cushing's syndrome.

Expression of interleukin-15 and inflammatory cytokines in skeletal muscles of STZ-induced diabetic rats: effect of resistance exercise training

Skeletal muscle atrophy is associated with type-1 diabetes. Skeletal muscle is the source of pro- and anti-inflammatory cytokines that can mediate muscle hypertrophy and atrophy, while resistance exercise can modulate both muscle mass and muscle cytokine expression. This study determined the effects of a 5-week resistance exercise training regimen on the expression of muscle cytokines in healthy and streptozotocin-induced diabetic rats, with special emphasis on interleukin-15 (IL-15), a muscle-derived cytokine proposed to be involved in muscle hypertrophy or responses to stress. Induction of diabetes reduced muscle weight in both the fast flexor hallucis longus (FHL) and slow soleus muscles, while resistance training preserved FHL muscle weight in diabetic rats. IL-15 protein content was increased by training in both FHL and soleus muscles, as well as serum, in normal and diabetic rats. With regard to proinflammatory cytokines, muscle IL-6 levels were increased in diabetic rats, while training decreased muscle IL-6 levels in diabetic rats; training had no effect on FHL muscle IL-6 levels in healthy rats. Also, tumor necrosis factor-alpha (TNF-α) and IL-1β levels were increased by diabetes, but not changed by training. In conclusion, we found that in diabetic rats, resistance training increased muscle and serum IL-15 levels, decreased muscle IL-6 levels, and preserved FHL muscle mass.

The proteasome inhibitor MG132 attenuates skeletal muscle atrophy in a rat model of chronic obstructive pulmonary disease

To investigate the effect of the proteasome inhibitor MG-132 on skeletal muscle atrophy in a rat model of chronic obstructive pulmonary disease (COPD) and its potential mechanisms. The COPD rat model was established by instillation of LPS and exposure to the cigarette smoke. Then the COPD rats were randomly divided into 3 groups (each group n = 12): COPD model control group, MG-132 high dose group (MG-132 0.1 mg·kg(-1)·d(-1)) and low dose group (MG-132 0.05 mg·kg(-1)·d(-1)), and normal control group. After 1 week and 4 week, 6 rats of each group were sacrificed, and then the following parameters were determined: the weight of the diaphragm muscle, the concentration of TNF-α in the serum and diaphragm via enzyme-linked immunosorbent assay (ELISA). Muscle atrophy F-box protein (MAFbx), NF-κBp65, and IκB-α mRNA levels were determined by RT-PCR. The protein levels of MAFbx, NF-κBp65 and IκB-α in diaphragm were measured by Western blot. The single factor analysis of variance was used for statistical analysis among the groups, while t test was used for comparison between 2 groups, and Pearson linear correlation analysis was also performed. The weight of diaphragm muscle from 1 week and 4 week normal control group [(0.99 ± 0.06) mg and (1.20 ± 0.04) mg] were reduced as compared to those of COPD model control group [(0.83 ± 0.09) mg and (1.01 ± 0.06) mg], high dose group [(0.85 ± 0.02) mg and (1.11 ± 0.06) mg], and low dose group [(0.83 ± 0.03) mg and (1.04 ± 0.02) mg]. The reduction of diaphragm muscle weight in the high dose group and the low dose group was significantly less than that in the COPD model control group, with a more marked difference as compared with the 4 week high dose group. The TNF-α levels in diaphragm from 4 week high dose group [(106 ± 8) ng/L] and low dose group [(122 ± 7) ng/L] were decreased as compared to that of the COPD model control group [(143 ± 24) ng/L]. The levels of NF-κBp65 and MAFbx mRNA from the 4 week high dose group (2.17 ± 0.42) and low dose group (1.74 ± 0.14) and the protein expression (1.13 ± 0.04 and 1.27 ± 0.05) were also decreased as compared to those of the COPD model control group (mRNA 2.81 ± 0.31 and 4.87 ± 0.34, protein expression 1.32 ± 0.04 and 1.44 ± 0.07). The levels of IκB-α mRNA and protein expression (0.96 ± 0.08 and 0.83 ± 0.06) were higher than those of the COPD model control group (0.25 ± 0.02 and 0.58 ± 0.06), (t = 1.57-24.9, P < 0.05). The levels of the TNF-α levels in serum and diaphragm were correlated positively with the levels of MAFbx and NF-κBp65 mRNA and protein expression (r = 0.672-0.875, P < 0.01), but negatively with the levels of IκB-α mRNA and protein expression (r = -0.656--0.927, P < 0.01). The proteasome inhibitor MG-132 significantly inhibited IκB-α degradation thus preventing NF-κB activation. This effect resulted in preventing skeletal muscle atrophy in the COPD rats.

Differential adaptation of glycolytic and oxidative muscles to hypoxia

BackgroundCOPD‐associated skeletal muscle atrophy is found in glycolytic rather than oxidative muscle fibers. We hypothesize that hypoxia is a trigger for this fiber type‐specific atrophy.MethodsMice were kept under normoxia or hypoxia. Oxygen levels were reduced stepwise to 8% during 48h, and maintained for 21 days. Food intake was monitored and mice were sacrificed at days 4 and 21.ResultsReduction of oxidative (Soleus) muscle weight was due to hypoxia‐induced hypophagia. Glycolytic (EDL) muscle weight reduction involved additional hypophagia‐independent effects. Cross sectional area (CSA) of individual fibers was reduced in glycolytic but not oxidative muscle. Expression of genes involved in proteasomal and lysosomal protein degradation, ER stress and glucocorticoid receptor (GR) signaling were increased in both muscles. In glycolytic muscle, upregulation could not be explained by hypophagia alone. Capillary contacts per fiber CSA increased in both muscles. In oxidative muscle, this was due to a reduction of the interstitial space, whereas in glycolytic muscle fiber CSA decreased.ConclusionsMuscle mass, muscle fiber CSA, proteolysis, ER‐stress and GR signaling are more affected by hypoxia in glycolytic than oxidative muscle. In oxidative, but not glycolytic muscle, these alterations are accounted for by hypophagia.Supported by the Dutch Top Institute Pharma (project # T1‐201).

Selectivity in the Reinnervation of the Lateral Gastrocnemius Muscle after Nerve Repair with Ethyl Cyanoacrylate in the Rat

There is a need for complementary surgical techniques that enable rapid and reliable primary repair of transected nerves. Previous studies after peripheral nerve transection and repair with synthetic adhesives have demonstrated regeneration to an extent comparable to that of conventional techniques. The aim of this study was to compare two different repair techniques on the selectivity of muscle reinnervation after repair and completed regeneration. We used the cholera toxin B technique of retrograde axonal tracing to evaluate the morphology, the number, and the three-dimensional location of α-motoneurons innervating the lateral gastrocnemius muscle and compared the results after repair with either ethyl cyanoacrylate (ECA) or epineural sutures of the transected parent sciatic nerve. In addition, we recorded the wet weight of the muscle. Six months after transection and repair of the sciatic nerve, the redistribution of the motoneuron pool was markedly disorganized, the motoneurons had apparently increased in number, and they were scattered throughout a larger volume of the spinal cord gray matter with a decrease in the synaptic coverage compared to controls. A reduction in muscle weight was observed as well. No difference in morphometric variables or muscle weight between the two repair methods could be detected. We conclude that the selectivity of motor reinnervation following sciatic nerve transection and subsequent repair with ECA is comparable to that following conventional micro suturing.

Comparison between Neurectomy and Botulinum Toxin A Injection for Denervated Skeletal Muscle

Neurectomy and botulinum toxin A (BoNT-A) injection cause denervated muscle atrophy, but questions remain about their clinical utility. We investigated time-series alterations of rat muscle weight, functional deficits, signaling pathways, and microscopic structures, to gain an understanding of the clinical implications. Between 2008 and 2009, the maximal calf circumference of patients for calf reduction either by neurectomy or BoNT-A injections were recorded for study. A rat skeletal muscle model was established through repeated or dose-adjusted BoNT-A injections and neurectomy. The survival, apoptosis pathways, functional deficits, and microscopic structures were investigated using Western blot, sciatic functional index (SFI), and transmission electron microscopy (TEM), respectively. The rat muscle weight ratio of the BoNT-A group had recovered to 89.3 +/- 3.8% by week 58, but it never recovered in the neurectomy group. Muscle weight reduction by BoNT-A not only depended on the dose, but additive effects were also obtained through repeated injections. Rat SFI demonstrated rapid recovery in both groups. Molecular expressions showed a coherent and biphasic pattern. p-Akt and apoptosis-inducing factor (AIF) were upregulated significantly, with a peak at 8 weeks in the neurectomy group (p < 0.01), but cleaved caspase-9 and caspase-3 showed no significant changes in either group. TEM findings showed irreversible and reversible inner-structure disruption and sarcomere discontinuity in the neurectomy and BoNT-A groups, respectively. We demonstrated that denervation induced lasting muscle weight and structural changes of different degrees. Muscle weight reduction by BoNT-A was related to frequency and dose. AIF-mediated caspase-independent apoptosis was significantly different for neurectomy and BoNT-A injection.

Long-term results of peripheral nerve repair: A comparison of nerve anastomosis with ethyl-cyanoacrylate and epineural sutures

Event Abstract Back to Event Long-term results of peripheral nerve repair: A comparison of nerve anastomosis with ethyl-cyanoacrylate and epineural sutures Thomas Landegren1* 1 Karolinska Institutet, Department of Clinical Science and Education, Sweden There is a need for complementary surgical techniques which offers rapid and reliable primary repair of transected nerves. Anastomosis of a nerve with synthetic adhesive following a lesion has previously been shown to indicate recovery to an extent comparable to that of conventional techniques. The aim of this study was to quantify the morphological and functional recovery and evaluate the selectivity of muscle reinnervation after transection and repair of rat sciatic nerve, and compare epineural sutures with a synthetic ethyl-cyanoacrylate tissue adhesive. Six month after repair, when reinnervation had well been completed the tibial branch to the lateral gastrocnemius muscle and the caudal sural cutaneous nerve were examined with electrophysiological measurements of motor and sensory conduction velocity, motor nerve action potentials, and quantitative histological examinations. Furthermore, cholera toxin B technique of retrograde axonal tracing was used to evaluate the morphology, the number and the three-dimensional location of a-motoneurons in L5 spinal cord, innervating the lateral gastrocnemius muscle and the results were put in relation to the recorded wet weight of the muscle. There was functional reinnervation of motor and sensory nerves in both groups, as shown by equivalent recovery of motor and sensory conduction velocities, and motor nerve action potentials. Histological examination showed no significant difference in the mean diameter, fibre density or the number of regenerated myelinated motor and sensory axons distal to the repair site between the two groups. Moreover, independent of repair method, the redistribution of the motoneuron pool were markedly disorganized, had increased apparently in number, and were scattered throughout a larger volume of the spinal cord grey matter with a decrease in the synaptic coverage compared to controls. A reduction in muscle weight was observed as well. Differences compared to controls were statistically significant. We conclude that anastomosis of the nerve with ethyl-cyanoacrylate adhesive supports morphological and functional recovery comparable to that of conventional epineural sutures after a unilateral lesion of the sciatic nerve in adult rats. Keywords: cyanoacrylate, motoneuron, Nerve repair, peripheral nerve, Regeneration, retrograde tracing, spinal misdirection, synthetic adhesive Conference: Karolinska Institutet 200 years anniversary Symposium on Traumatic Injuries in the Nervous System, Stockholm, Sweden, 15 Sep - 16 Sep, 2010. Presentation Type: Presentation Topic: Traumatic Injuries in the Nervous System Citation: Landegren T (2010). Long-term results of peripheral nerve repair: A comparison of nerve anastomosis with ethyl-cyanoacrylate and epineural sutures. Front. Neurol. Conference Abstract: Karolinska Institutet 200 years anniversary Symposium on Traumatic Injuries in the Nervous System. doi: 10.3389/conf.fneur.2010.56.00011 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 07 Sep 2010; Published Online: 21 Sep 2010. * Correspondence: Dr. Thomas Landegren, Karolinska Institutet, Department of Clinical Science and Education, Stockholm, Sweden, Thomas.landegren@ki.se Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Thomas Landegren Google Thomas Landegren Google Scholar Thomas Landegren PubMed Thomas Landegren Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The effect of a low dose of clenbuterol on rat soleus muscle submitted to joint immobilization

The aim of the present study was to evaluate the effect of joint immobilization on morphometric parameters and glycogen content of soleus muscle treated with clenbuterol. Male Wistar (3-4 months old) rats were divided into 4 groups (N = 6 for each group): control, clenbuterol, immobilized, and immobilized treated with clenbuterol. Immobilization was performed with acrylic resin orthoses and 10 microg/kg body weight clenbuterol was administered subcutaneously for 7 days. The following parameters were measured the next day on soleus muscle: weight, glycogen content, cross-sectional area, and connective tissue content. The clenbuterol group showed an increase in glycogen (81.6%, 0.38 +/- 0.09 vs 0.69 +/- 0.06 mg/100 g; P < 0.05) without alteration in weight, cross-sectional area or connective tissue compared with the control group. The immobilized group showed a reduction in muscle weight (34.2%, 123.5 +/- 5.3 vs 81.3 +/- 4.6 mg; P < 0.05), glycogen content (31.6%, 0.38 +/- 0.09 vs 0.26 +/- 0.05 mg/100 mg; P < 0.05) and cross-sectional area (44.1%, 2574.9 +/- 560.2 vs 1438.1 +/- 352.2 microm(2); P < 0.05) and an increase in connective tissue (216.5%, 8.82 +/- 3.55 vs 27.92 +/- 5.36%; P < 0.05). However, the immobilized + clenbuterol group showed an increase in weight (15.9%; 81.3 +/- 4.6 vs 94.2 +/- 4.3 mg; P < 0.05), glycogen content (92.3%, 0.26 +/- 0.05 vs 0.50 +/- 0.17 mg/100 mg; P < 0.05), and cross-sectional area (19.9%, 1438.1 +/- 352.2 vs 1724.8 +/- 365.5 microm(2); P < 0.05) and a reduction in connective tissue (52.2%, 27.92 +/- 5.36 vs 13.34 +/- 6.86%; P < 0.05). Statistical analysis was performed using Kolmogorov-Smirnov and homoscedasticity tests. For the muscle weight and muscle glycogen content, two-way ANOVA and the Tukey test were used. For the cross-sectional area and connective tissue content, Kruskal-Wallis and Tukey tests were used. This study emphasizes the importance of anabolic pharmacological protection during immobilization to minimize skeletal muscle alterations resulting from disuse.

O efeito do estrógeno nas reservas glicogênicas de musculoesqueléticos desnervados de ratas

The estrogen effect on glycogen reserves of denervated skeletal muscles of female rats Objective: To evaluate the effects of estrogen on muscles in female rats subjected to hindlimb denervation. Methods: Female Wistar rats were divided into five groups (n=6): control; denervated 7 days; denervated 15 days; denervated treated with estrogen (200μg/rat, subcutaneously, daily) for 7 days; and denervated treated with estrogen for 15 days. After the experimental periods, glycogen (GLY) evaluations were performed on the soleus (S), white gastrocnemius (WG) and red gastrocnemius (RG), and the soleus was weighed. The statistical analysis was performed using the normality test, ANOVA and Tukey test (p<0.05). Results: The denervation caused a reduction (p<0.05) in GLY over a 7-day period (S: 44%, WG: 32%; RG: 32%) and 15-day period (S: 62%, WG: 44%; RG: 53%), and also S weight reduction (7 days: 29.7%; 15 days: 36.6%). However, the estrogen treatment caused elevation (p<0.05) of GLY under this condition, both over 7 days (S: 19%; WG: 60%; RG: 18%) and over 15 days (S: 52%; WG: 51%; RG: 11%), but it was not enough to minimize the muscle weight reduction. Conclusions: The treatment with low doses of estrogen minimized the metabolic alterations induced by denervation, but it was not effective in interfering in the weight loss of the soleus muscle. This suggests that the hormone acts by enabling chemical-metabolic protection that acts like the insulin route, but the effect is multifactorial and depends on the dose, manner and duration of the treatment, as well as the time since denervation.

Supplementation with Dietary Leucine to a Protein-Deficient Diet Suppresses Myofibrillar Protein Degradation in Rats

Muscle mass is regulated by the synthesis and degradation of muscle protein, which in turn are affected by aging, several catabolic diseases, and malnutrition. Amino acids, particularly leucine, are known to stimulate muscle protein synthesis and suppress muscle protein degradation, although their long-term effects are unclear. The objective of our research was to elucidate whether long-term feeding of a protein-free or low-protein diet supplemented with leucine suppresses myofibrillar protein degradation. The rate of myofibrillar protein degradation was measured by the rate of release of 3-methylhistidine (MeHis) from isolated extensor digitorum longus (EDL) muscle. The weight of gastrocnemius muscle decreased in rats fed a protein-free diet for 7 d; however, a leucine-supplemented (1.5%) diet tended to suppress this decrease. The release of MeHis from EDL muscle was increased by the protein-free diet and decreased by the feeding of a diet supplemented with leucine to the level of a 20% casein diet. When rats were fed a 5% casein diet, the gastrocnemius muscle weight decreased and MeHis release from EDL muscle increased compared to those fed a 20% casein diet. However, feeding of a 5% casein diet supplemented with leucine (1.15%) reduced muscle weight loss and MeHis release. These results suggest that long-term feeding of leucine suppresses the rate of myofibrillar protein degradation and muscle weight loss in rats fed a protein-deficient diet.

Collapse of the fishery for Iceland scallop (Chlamys islandica) in Breidafjordur, West Iceland

AbstractJonasson, J. P., Thorarinsdottir, G., Eiriksson, H., Solmundsson, J., and Marteinsdottir, G. 2007. Collapse of the fishery for Iceland scallop (Chlamys islandica) in Breidafjordur, West Iceland. – ICES Journal of Marine Science, 64: 298–308. The stock index of the Iceland scallop (Chlamys islandica) in Breidafjordur on the west coast of Iceland has declined drastically in recent years. Total fishing mortality was very high throughout the study period from 1993 to 2003, a period characterized by a steady increase in summer sea surface temperature, in 2003 reaching the highest estimated level of the previous century. Between 1998 and 2005, estimates of chlorophyll a (food availability) fluctuated with periods of low chlorophyll followed by a reduction in muscle weight and high natural mortality. High levels of natural mortality were observed in the main fishing area in the southern part of Breidafjordur. There the stock index had been declining since 1994. Recruitment to the fishable stock was highly variable during the study period, with low recruitment towards the end of the 1990s. Subsequently the fishery has been on relatively few year classes, and the stock has been fragile because of several years of poor recruitment and high natural mortality. Consequently, the stock appeared unable to withstand the fishing pressure and declined to historically low levels, leading to a halt to fishing in 2004.

Deficiency of the Bax gene attenuates denervation-induced apoptosis

Apoptosis has been implicated in mediating denervation-induced muscle wasting. In this study we determined the effect of interference of apoptosis on muscle wasting during denervation by using mice genetically deficient in pro-apoptotic Bax. After denervation, muscle wasting was evident in both wild-type and Bax(-/-) muscles but reduction of muscle weight was attenuated in Bax(-/-) mice. Apoptotic DNA fragmentation increased in wild-type denervated muscles whereas there was no statistical increase in DNA fragmentation in denervated muscles from Bax(-/-) mice. Mitochondrial AIF and Smac/DIABLO releases and Bcl-2, p53 and HSP27 increased whereas XIAP and MnSOD decreased to a similar extent in muscles from wild-type and Bax(-/-) mice following denervation. Mitochondrial cytochrome c release was elevated in denervated muscles from wild-type mice but the increase was suppressed in muscles from Bax(-/-) mice. Increases in caspase-3 and -9 activities and oxidative stress markers H(2)O(2), MDA/4-HAE and nitrotyrosine were all evident in denervated muscles from wild-type mice but these changes were absent in muscles from Bax(-/-) mice. Moreover, ARC increased exclusively in denervated Bax(-/-) muscle. Our data indicate that under conditions of denervation, pro-apoptotic signalling is suppressed and muscle wasting is attenuated when the Bax gene is lacking. These findings suggest that interventions targeting apoptosis may be valuable in ameliorating denervation-associated pathologic muscle wasting in certain neuromuscular disorders that involve partial or full denervation.