Akt‐dependent and Akt‐independent pathways are involved in protein synthesis activation during reloading of disused soleus muscle

Introduction: The purpose of our study was to assess the contribution of insulin growth factor‐1–dependent and phosphatidic acid‐dependent signaling pathways to activation of protein synthesis (PS) in rat soleus muscle during early recovery from unloading. Methods: Wistar rats were divided into: Control, 14HS [14‐day hindlimb suspension (HS)], 3R+placebo (3‐day reloading + saline administration), 3R+Wort (3‐day reloading + wortmannin administration), 3R+But (3‐day reloading + 1‐butanol administration). SUnSET and Western blot analyses were used in this study. Results: Wortmannin and 1‐butanol induced a decrease in protein kinase B (phospho‐Akt) and the rate of PS (P < 0.05) versus Control. In 3R+placebo and 3R+Wort, phosphorylation of glycogen synthase kinase 3 beta (phospho‐GSK‐3β) was increased versus Control (P < 0.05). Wortmannin administration during reloading did not alter phospho‐p70S6K (70 kDa ribosomal protein S6 kinase) versus 3R+placebo. In 3R+But, there was a decline in phospho‐GSK‐3β versus 3R+placebo and Control. In 3R+But, there was a decrease in phopho‐p70S6K (P < 0.05) versus 3R+placebo. Conclusions: These results suggest that PS activation during 3‐day reloading following 14HS involves both Akt‐dependent and Akt‐independent pathways. Muscle Nerve 55 : 393–399, 2017     

Apigenin inhibits sciatic nerve denervation–induced muscle atrophy

Introduction: Apigenin (AP) has been reported to elicit anti‐inflammatory effects. In this study, we investigated the effect of AP on sciatic nerve denervation–induced muscle atrophy. Methods: Sciatic nerve–denervated mice were fed a 0.1% AP‐containing diet for 2 weeks. Muscle weight and cross‐sectional area (CSA), and the expression of atrophic genes and inflammatory cytokines in the gastrocnemius were analyzed. Results: Denervation significantly induced muscle atrophy. However, values for muscle weight and CSA were greater in the denervated muscle of the AP mice than the controls. AP suppressed the expression of MuRF1, but upregulated both myosin heavy chain (MHC) and MHC type IIb. AP also significantly suppressed expression of tumor necrosis‐alpha in the gastrocnemius and soleus muscles, and interleukin‐6 expression in the soleus muscle. Discussion: AP appears to inhibit denervation‐induced muscle atrophy, which may be due in part to its inhibitory effect on inflammatory processes within muscle. Muscle Nerve 58 : 314–318, 2018     

Branched‐chain amino acids protect against dexamethasone‐induced soleus muscle atrophy in rats

We investigated the utility of branched‐chain amino acids (BCAA) in dexamethasone‐induced muscle atrophy. Dexamethasone (600 μg/kg, intraperitoneally) and/or BCAA (600 mg/kg, orally) were administered for 5 days in rats, and the effect of BCAA on dexamethasone‐induced muscle atrophy was evaluated. Dexamethasone decreased total protein concentration of rat soleus muscles. Concomitant administration of BCAA reversed the decrease. Dexamethasone decreased mean cross‐sectional area of soleus muscle fibers, which was reversed by BCAA. Dexamethasone increased atrogin‐1 expression, which has been reported to play a pivotal role in muscle atrophy. The increased expression of atrogin‐1 mRNA was significantly attenuated by BCAA. Furthermore, dexamethasone‐induced conversion from microtubule‐associated protein 1 light chain 3 (LC3)‐I to LC3‐II, which is an indicator of autophagy, was blocked by BCAA. These findings suggest that BCAA decreased protein breakdown to prevent muscle atrophy. BCAA administration appears to be useful for prevention of steroid myopathy. Muscle Nerve, 2010     

Lean and obese Zucker rats exhibit different patterns of p70s6 kinase regulation in the tibialis anterior muscle in response to high‐force muscle contraction

Increased phosphorylation of the 70‐kDa ribosomal S6 kinase (p70S6k) signaling is strongly correlated with the degree of muscle adaptation following exercise. Herein we compare the phosphorylation of p70S6k, Akt, and mammalian target of rapamycin (mTOR) in the tibialis anterior (TA) muscles of lean and obese Zucker rats following a bout of eccentric exercise. Exercise increased p70S6k (Thr389) phosphorylation immediately after (33.3 ± 7.2%) and during [1 h (24.0 ± 14.9%) and 3 h (24.6 ± 11.3%)] recovery in the lean TA and at 3 h (33.5 ± 8.0%) in the obese TA Zucker rats. mTOR (Ser2448) phosphorylation was elevated in the lean TA immediately after exercise (96.5 ± 40.3%) but remained unaltered in the obese TA. Exercise increased Akt (Thr308) and Akt (Ser473) phosphorylation in the lean but not the obese TA. These results suggest that insulin resistance is associated with alterations in the ability of muscle to activate p70S6k signaling following an acute bout of exercise. Muscle Nerve 39: 503–511 2009     

Effects of slow muscle stretch on the responses of primary and secondary endings to small amplitude periodic stretches in de-efferented soleus muscle spindles

The responses of primary and secondary endings of de-efferented soleus spindles to small amplitude periodic stretches superimposed on slow ramp stretches have been studied. For primary endings, the responses become progressively larger especially during the last period of the ramp whereas for secondary endings, after an initial period of moderate growth, the amplitude of the responses display a relative reduction precisely when the responses of the primary endings are the largest. These differences can be interpreted in terms of progressive increase in stiffness of the striated polar portions of the intrafusal muscle fibers.     

高频正弦波振动对制动大鼠比目鱼肌萎缩的对抗作用

背景：肌梭的传入冲动减少与失用性肌萎缩的发生密切相关。高频正弦波振动能够兴奋肌梭，肌梭传入活动的增加可以增强骨骼肌的肌电活动，理论上能对抗比目鱼肌萎缩。 目的：验证高频正弦波振动对后肢制动大鼠比目鱼肌萎缩的对抗作用。 设计、时间及地点：随机对照动物实验，于2008-05/2009-01在西安交通大学医学院教育部重点实验室完成。 材料：SPF级健康成年雌性SD大鼠30只，按随机配对原则分为3组：正常对照组、制动组、振动组，每组10只动物。 方法：除正常对照组外，采用大鼠后肢制动(石膏固定)作为肌肉失用模型，在后肢制动的14 d期间，振动组大鼠制动肢体的比目鱼肌部位实施高频振动(100 Hz；500 μm，480 s/d)。之后取各组大鼠比目鱼肌。 主要观察指标：①称其湿质量，计算出湿质量体质量比。②采用酶组化染色及计算机图像分析技术测定骨骼肌纤维的横截面积以及Ⅰ、Ⅱ型肌纤维的构成比。 结果：①14 d后，制动组大鼠比目鱼肌湿质量、湿质量/体质量及肌纤维横截面积与对照组相比明显减小(P < 0.05)；同时，制动组大鼠比目鱼肌Ⅰ型肌纤维所占比例下降而Ⅱ型肌纤维比例增高(P < 0.05)。②制动加高频振动组大鼠14 d后，与制动组相比，比目鱼肌的湿质量、湿质量/体质量及肌纤维横截面积均有明显增大(P < 0.05)。 结论：高频正弦波振动可有效地对抗(预防)制动引起的比目鱼肌萎缩。     

Role of gelatinases in disuse‐induced skeletal muscle atrophy

Gelatinases are a subgroup of the family of matrix metalloproteinases, which contains two members—gelatinase A and B. These enzymes play an important role in basement membrane homeostasis. Previous studies have associated basement membrane degradation with skeletal muscle atrophy. However, the specific contribution of gelatinases to the pathobiology of muscle atrophy remains unknown. In this study we examined the specific roles of gelatinase A and B in disuse‐induced skeletal muscle atrophy using knockout mice. Although both gelatinase A and B are highly upregulated in disused muscle, only gelatinase A null mice had significantly reduced muscle atrophy as compared to wildtype littermates. Type IV collagen and laminin, two major components of basement membrane, were relatively well‐preserved in disused muscle in gelatinase A null mice, but not in gelatinase B null mice. These findings suggest that gelatinase A, and not gelatinase B, plays a critical role in disuse‐induced skeletal muscle atrophy. Muscle Nerve, 2010     

A model of muscle atrophy using cast immobilization in mice

We describe a new cast-immobilization protocol to induce muscle atrophy in the lower hindlimb muscles of mice. Bilateral cast immobilization for 2 weeks in a shortened position resulted in a significant loss of muscle size and strength in the soleus and extensor digitorum longus. The availability of a model of cast immobilization in mice may benefit future studies targeting genetic or cell therapy interventions of muscle atrophy in transgenic and mutant mice strains.     

Role of AMP‐Activated Protein Kinase Activators in Antiproliferative Multi‐Drug Pituitary Tumour Therapies: Effects of Combined Treatments with Compounds Affecting the mTOR‐p70S6 Kinase Axis in Cultured Pituitary Tumour Cells

AMP‐activated protein kinase (AMPK) is activated under conditions that deplete cellular ATP levels and elevate AMP levels. We have recently shown that AMPK can represent a valid target for improving the medical treatment of growth hormone (GH)‐secreting pituitary adenomas and the effects of its activation or inhibition in pituitary tumour cells are worthy of further characterisation. We aimed to determine whether AMPK may have a role in combined antiproliferative therapies based on multiple drugs targeting cell anabolic functions at different levels in pituitary tumour cells to overcome the risk of cell growth escape phenomena. Accordingly, we tried to determine whether a rationale exists in combining compounds activating AMPK with compounds targeting the phosphatidylinositol‐3‐kinase (PI3K)/Akt/mTOR/p70S6K signalling pathway. AMPK down‐regulation by specific small‐interfering RNAs confirmed that activated AMPK had a role in restraining growth of GH3 cells. Hence, we compared the effects of compounds directly targeting the mTOR‐p70S6K axis, namely the mTOR inhibitor rapamycin and the p70S6K inhibitor PF‐4708671, with the effects of the AMPK activator 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICAR) on cell signalling and cell growth, in rat pituitary GH3 cells. AICAR was able to reduce growth factor‐induced p70S6K activity, as shown by the decrease of phospho‐p70S6K levels. However, it was far less effective than rapamycin and PF‐4708671. We observed significant differences between the growth inhibitory effects of the three compounds in GH3 and GH1 cells. Interestingly, PF‐4708671 was devoid of any effect. AICAR was at least as effective as rapamycin and the co‐treatment was more effective than single treatments. AICAR induced apoptosis of GH3 cells, whereas rapamycin caused preferentially a decrease of cell proliferation. Finally, AICAR and rapamycin differed in their actions on growth factor‐induced extracellular signal regulated kinase 1/2 phosphorylation. In conclusion, the results of the present study suggest the increased efficacy of combined antiproliferative therapies, including rapamycin analogues and AMPK activators in GH‐secreting pituitary tumours, as a result of complementary and only partially overlapping mechanisms of action.     

Normalization reduces the spatial dependency of the jaw‐stretch reflex activity in the human masseter muscle

The jaw‐stretch reflex is the short‐latency response in the jaw‐closing muscles after a sudden stretch. The hypothesis whether normalization of the jaw‐stretch reflex amplitude with respect to prestimulus electromyographic (EMG) activity will make the amplitude more independent of the location of the electrodes over the masseter muscle was tested. A 5 × 6 electrode grid was used to record the jaw‐stretch reflex from 25 sites over the right masseter muscle of 15 healthy men. The results showed that there was a significant site dependency of the prestimulus EMG activity and the reflex amplitude. High cross‐correlation coefficients were found between the spatial distribution of mean prestimulus EMG activities and reflex amplitude. When the reflex amplitude was normalized with respect to the prestimulus EMG activity, no site dependency was found. In conclusion, normalization of the jaw‐stretch reflex amplitude by the prestimulus EMG activity strongly reduces its spatial dependency. Muscle Nerve, 2010     

Training at non‐damaging intensities facilitates recovery from muscle atrophy

Introduction: Resistance training promotes recovery from muscle atrophy, but optimum training programs have not been established. We aimed to determine the optimum training intensity for muscle atrophy. Methods: Mice recovering from atrophied muscles after 2 weeks of tail suspension underwent repeated isometric training with varying joint torques 50 times per day. Results: Muscle recovery assessed by maximal isometric contraction and myofiber cross‐sectional areas (CSAs) were facilitated at 40% and 60% maximum contraction strength (MC), but at not at 10% and 90% MC. At 60% and 90% MC, damaged and contained smaller diameter fibers were observed. Activation of myogenic satellite cells and a marked increase in myonuclei were observed at 40%, 60%, and 90% MC. Conclusions: The increases in myofiber CSAs were likely caused by increased myonuclei formed through fusion of resistance‐induced myofibers with myogenic satellite cells. These data indicate that resistance training without muscle damage facilitates efficient recovery from atrophy. Muscle Nerve 55 : 243–253, 2017     

Focal atrophy of the multifidus muscle in lumbosacral radiculopathy

A patient with compelling clinical and electrodiagnostic evidence of a right L5 radiculopathy had focal atrophy of the multifidus at the appropriate level, which served to confirm the radicular nature of the process. The multifidus muscles are innervated by a single root, in contrast to the polysegmental innervation of the rest of the paraspinal muscle mass. Imaging studies may complement needle electromyography in the evaluation of this important structure. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:1350–1353, 1998.     

Changes in primary muscle spindle ending excitability induced by a ramp-and-hold stretch

36 primary (la) muscle spindle afferents from the tibial anterior muscle of the cat were subjected to a ramp-and-hold stretch (stretch rate 10 mm/s, stretch amplitude 5 or 8.5 mm) of the muscle, on which a sinusoidal stretch (50 Hz) of four different amplitudes (25, 50, 250 and 500 μm) was superimposed. In 54 discharge patterns a la afferent subjected to a ramp-and-hold stretch with a sinusoidal stretch superimposed responded only to the superimposed sinusoidal stretch. In 25 of the cases the la afferent responded with an one-to-one driven action potential (AP) and in 29 of the cases with two AN per sinusoidal stretch. For these 54 discharge patterns the phase of the sinusoidal cycle was determined at which each AP occurred. Where the la afferent responded with one AP per cycle an accelerating phase advance was observed during the ramp stage of the underlying ramp-and-hold stretch and a decelerating phase advance during the plateau. This phase shift means that the excitability of the site generating the AP increased during the ramp stage and decreased during the plateau. If the la afferent responded with two AN per superimposed cycle, the second AP per cycle evinced a decelerating phase advance during the ramp and an accelerating phase advance during the plateau. The phase of the second AP per cycle showed a second, contrary change in excitability at the AP generating site. The excitability decreased during the ramp and increased during the plateau. The first kind of excitability change is interpreted as a consequence of an inward current at the AP generating site. The second, contrary type of excitability points to an interplay between an inward and an outward current. An increasing outward current lowers the excitability for the second AP per cycle during the ramp. A decreasing outward current raises the excitability during the plateau.     

Effect of ethanol on stretch response of muscle receptors in cats

The response of muscle spindles and tendon organs to steady and sinusoidal muscle stretch was investigated at different blood alcohol concentrations (BAC). After initial anesthesia (pentobarbital), cats were spinalized, the lumbar ventral roots cut and the gastrocnemius muscles of one hindleg prepared for controlled stretching. The animals were paralyzed and artificial respiration was applied. Action potentials from isolated Ia/Ib/II afferent fibers could be recorded.Under steady stretch conditions, all fibers responded to an increasing BAC with an increase in firing rate. This could be observed already at 0.8 mg/ml BAC. The increase in discharge rate reached at the most 80 imp/s. During intoxication the regularity of firing was higher than in the no-alcohol situation. At blood alcohol concentrations higher than 5 mg/ml, the neuronal activity suddenly dropped to zero, exhibiting an irregular impulse pattern. The increase in discharge rate at steady stretch is regarded to be of minor significance in the explanation of the impairment of motor performance under ethanol.When sinusoidal stretch was applied, the increase in the mean discharge rate was smaller than at steady stretch conditions. Up to about 10 mg/ml BAC the periodical modulation of firing rate during sinusoidal stretch of a large amplitude remained mainly unchanged. After the discharge rate had dropped to zero for the steady stretch condition at high BAC, elicitation of action potentials was always possible using dynamic stretch.     

翼点开颅术后颞肌萎缩的原因及防治

目的探讨翼点开颅术后颢肌萎缩的原因及防治措施.方法对164例病人采用术中保护颞浅动脉,骨膜下逆行分离颞肌,必要时切除颧弓,保持颞肌正常张力等方法保护颞肌.结果本组病人无颞肌萎缩、颞前区瘪陷,两边颞肌对称,张口和咬合功能正常.结论颞肌萎缩的原因:不正当的分离、过分的牵拉、肌肉复位时挤拉等直接损害颞肌;供应颞肌的血管阻断致肌肉缺血;颞肌部分或全部失神经支配;颞肌复位时没有维持合适的肌肉张力.针对原因术中进行适当操作,可完全杜绝术后颞肌萎缩的发生.     

Differential effects of plantar cutaneous afferent excitation on soleus stretch and H‐reflex

Previous studies have demonstrated that plantar cutaneous afferents can adjust motoneuron excitability, which may contribute significantly to the control of human posture and locomotion. However, the role of plantar cutaneous afferents in modulating the excitability of stretch and H‐reflex with respect to the location of their excitation remains unclear. In the present study, it was hypothesized that electrical stimulation delivered to the sole of the foot might be followed by modulation of spinal excitability that depends on: (1) the stimulation location and (2) the reflex studied. In these experiments, conditioned and unconditioned stretch and H‐reflexes were evoked in 16 healthy subjects in a seated position. Both reflexes were conditioned by non‐noxious electrical plantar cutaneous afferent stimulation at two different sites, the heel and metatarsal regions, at four different conditioning–test (CT) intervals. The conditioning stimulation delivered to the heel caused a significant facilitation of the soleus stretch reflex for all CT intervals, whereas the soleus H‐reflex had significant facilitation only at CT interval of 50 ms and significant inhibition at longer CT intervals. Stimulation delivered to the metatarsal region, however, resulted mainly in reduced stretch and H‐reflex sizes. This study extends the reported findings on the contribution of plantar cutaneous afferents within spinal interneuron reflex circuits as a function of their location and the reflex studied. Muscle Nerve, 2008     

Olivopontocerebellar atrophy of neonatal onset with muscle hypertonia in two siblings

Two siblings (one girl and one boy) with familial infantile olivopontocerebellar atrophy (OPCA) are reported. The brain pathology in one child revealed marked hypoplasia of phylogenetically new parts of the pons and medulla (pontine nuclei and inferior olivary nuclei) associated with hypoplasia of the neocerebellum. The clinical features were severe muscle hypertonia, hyperreflexia, multiple joint contractures, failure to thrive and respiratory insufficiency. Laboratory examinations including hematology, blood chemistry, very long chain fatty acids, analysis of amino acids in serum and urine, and organic acids in urine, and chromosomal analysis, revealed no abnormalities. The diagnosis of OPCA was established prior to death by magnetic resonance imaging (MRI) in one child. These cases may be atypical because the corticospinal tract and dentate nucleus were involved, in addition to OPCA.