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Sample records for adult mammalian muscle

  1. Constitutive properties of adult mammalian cardiac muscle cells

    NASA Technical Reports Server (NTRS)

    Zile, M. R.; Richardson, K.; Cowles, M. K.; Buckley, J. M.; Koide, M.; Cowles, B. A.; Gharpuray, V.; Cooper, G. 4th

    1998-01-01

    BACKGROUND: The purpose of this study was to determine whether changes in the constitutive properties of the cardiac muscle cell play a causative role in the development of diastolic dysfunction. METHODS AND RESULTS: Cardiocytes from normal and pressure-hypertrophied cats were embedded in an agarose gel, placed on a stretching device, and subjected to a change in stress (sigma), and resultant changes in cell strain (epsilon) were measured. These measurements were used to examine the passive elastic spring, viscous damping, and myofilament activation. The passive elastic spring was assessed in protocol A by increasing the sigma on the agarose gel at a constant rate to define the cardiocyte sigma-versus-epsilon relationship. Viscous damping was assessed in protocol B from the loop area between the cardiocyte sigma-versus-epsilon relationship during an increase and then a decrease in sigma. In both protocols, myofilament activation was minimized by a reduction in [Ca2+]i. Myofilament activation effects were assessed in protocol C by defining cardiocyte sigma versus epsilon during an increase in sigma with physiological [Ca2+]i. In protocol A, the cardiocyte sigma-versus-epsilon relationship was similar in normal and hypertrophied cells. In protocol B, the loop area was greater in hypertrophied than normal cardiocytes. In protocol C, the sigma-versus-epsilon relation in hypertrophied cardiocytes was shifted to the left compared with normal cells. CONCLUSIONS: Changes in viscous damping and myofilament activation in combination may cause pressure-hypertrophied cardiocytes to resist changes in shape during diastole and contribute to diastolic dysfunction.

  2. Mammalian masticatory muscles: homology, nomenclature, and diversification.

    PubMed

    Druzinsky, Robert E; Doherty, Alison H; De Vree, Frits L

    2011-08-01

    There is a deep and rich literature of comparative studies of jaw muscles in mammals but no recent analyses employ modern phylogenetic techniques to better understand evolutionary changes that have occurred in these muscles. In order to fully develop and utilize the Feeding Experiments End-user Database (FEED), we are constructing a comprehensive ontology of mammalian jaw muscles. This process has led to a careful consideration of nomenclature and homologies of the muscles and their constituent parts. Precise determinations of muscle attachments have shown that muscles with similar names are not necessarily homologous. Using new anatomical descriptions derived from the literature, we defined character states for the jaw muscles in diverse mammalian species. We then mapped those characters onto a recent phylogeny of mammals with the aid of the Mesquite software package. Our data further elucidate how muscle groups associated with the feeding apparatus differ and have become highly specialized in certain mammalian orders, such as Rodentia, while remaining conserved in other orders. We believe that careful naming of muscles and statistical analyses of their distributions among mammals, in association with the FEED database, will lead to new, significant insights into the functional, structural, and evolutionary morphology of the jaw muscles.

  3. Historical Perspectives: plasticity of mammalian skeletal muscle.

    PubMed

    Pette, D

    2001-03-01

    More than 40 years ago, the nerve cross-union experiment of Buller, Eccles, and Eccles provided compelling evidence for the essential role of innervation in determining the properties of mammalian skeletal muscle fibers. Moreover, this experiment revealed that terminally differentiated muscle fibers are not inalterable but are highly versatile entities capable of changing their phenotype from fast to slow or slow to fast. With the use of various experimental models, numerous studies have since confirmed and extended the notion of muscle plasticity. Together, these studies demonstrated that motoneuron-specific impulse patterns, neuromuscular activity, and mechanical loading play important roles in both the maintenance and transition of muscle fiber phenotypes. Depending on the type, intensity, and duration of changes in any of these factors, muscle fibers adjust their phenotype to meet the altered functional demands. Fiber-type transitions resulting from multiple qualitative and quantitative changes in gene expression occur sequentially in a regular order within a spectrum of pure and hybrid fiber types.

  4. Nitric oxide negatively regulates mammalian adult neurogenesis

    NASA Astrophysics Data System (ADS)

    Packer, Michael A.; Stasiv, Yuri; Benraiss, Abdellatif; Chmielnicki, Eva; Grinberg, Alexander; Westphal, Heiner; Goldman, Steven A.; Enikolopov, Grigori

    2003-08-01

    Neural progenitor cells are widespread throughout the adult central nervous system but only give rise to neurons in specific loci. Negative regulators of neurogenesis have therefore been postulated, but none have yet been identified as subserving a significant role in the adult brain. Here we report that nitric oxide (NO) acts as an important negative regulator of cell proliferation in the adult mammalian brain. We used two independent approaches to examine the function of NO in adult neurogenesis. In a pharmacological approach, we suppressed NO production in the rat brain by intraventricular infusion of an NO synthase inhibitor. In a genetic approach, we generated a null mutant neuronal NO synthase knockout mouse line by targeting the exon encoding active center of the enzyme. In both models, the number of new cells generated in neurogenic areas of the adult brain, the olfactory subependyma and the dentate gyrus, was strongly augmented, which indicates that division of neural stem cells in the adult brain is controlled by NO and suggests a strategy for enhancing neurogenesis in the adult central nervous system.

  5. DNA Transfection of Mammalian Skeletal Muscles using In Vivo Electroporation

    PubMed Central

    DiFranco, Marino; Quinonez, Marbella; Capote, Joana; Vergara, Julio

    2009-01-01

    A growing interest in cell biology is to express transgenically modified forms of essential proteins (e.g. fluorescently tagged constructs and/or mutant variants) in order to investigate their endogenous distribution and functional relevance. An interesting approach that has been implemented to fulfill this objective in fully differentiated cells is the in vivo transfection of plasmids by various methods into specific tissues such as liver1, skeletal muscle2,3, and even the brain4. We present here a detailed description of the steps that must be followed in order to efficiently transfect genetic material into fibers of the flexor digitorum brevis (FDB) and interosseus (IO) muscles of adult mice using an in vivo electroporation approach. The experimental parameters have been optimized so as to maximize the number of muscle fibers transfected while minimizing tissue damages that may impair the quality and quantity of the proteins expressed in individual fibers. We have verified that the implementation of the methodology described in this paper results in a high yield of soluble proteins, i.e. EGFP and ECFP3, calpain, FKBP12, β2a-DHPR, etc. ; structural proteins, i.e. minidystrophin and α-actinin; and membrane proteins, i.e. α1s-DHPR, RyR1, cardiac Na/Ca2+ exchanger , NaV1.4 Na channel, SERCA1, etc., when applied to FDB, IO and other muscles of mice and rats. The efficient expression of some of these proteins has been verified with biochemical3 and functional evidence5. However, by far the most common confirmatory approach used by us are standard fluorescent microscopy and 2-photon laser scanning microscopy (TPLSM), which permit to identify not only the overall expression, but also the detailed intracellular localization, of fluorescently tagged protein constructs. The method could be equally used to transfect plasmids encoding for the expression of proteins of physiological relevance (as shown here), or for interference RNA (siRNA) aiming to suppress the

  6. DNA transfection of mammalian skeletal muscles using in vivo electroporation.

    PubMed

    DiFranco, Marino; Quinonez, Marbella; Capote, Joana; Vergara, Julio

    2009-10-19

    A growing interest in cell biology is to express transgenically modified forms of essential proteins (e.g. fluorescently tagged constructs and/or mutant variants) in order to investigate their endogenous distribution and functional relevance. An interesting approach that has been implemented to fulfill this objective in fully differentiated cells is the in vivo transfection of plasmids by various methods into specific tissues such as liver, skeletal muscle, and even the brain. We present here a detailed description of the steps that must be followed in order to efficiently transfect genetic material into fibers of the flexor digitorum brevis (FDB) and interosseus (IO) muscles of adult mice using an in vivo electroporation approach. The experimental parameters have been optimized so as to maximize the number of muscle fibers transfected while minimizing tissue damages that may impair the quality and quantity of the proteins expressed in individual fibers. We have verified that the implementation of the methodology described in this paper results in a high yield of soluble proteins, i.e. EGFP and ECFP, calpain, FKBP12, beta2a-DHPR, etc. ; structural proteins, i.e. minidystrophin and alpha-actinin; and membrane proteins, i.e. alpha1s-DHPR, RyR1, cardiac Na/Ca(2+) exchanger , NaV1.4 Na channel, SERCA1, etc., when applied to FDB, IO and other muscles of mice and rats. The efficient expression of some of these proteins has been verified with biochemical and functional evidence. However, by far the most common confirmatory approach used by us are standard fluorescent microscopy and 2-photon laser scanning microscopy (TPLSM), which permit to identify not only the overall expression, but also the detailed intracellular localization, of fluorescently tagged protein constructs. The method could be equally used to transfect plasmids encoding for the expression of proteins of physiological relevance (as shown here), or for interference RNA (siRNA) aiming to suppress the

  7. Inward rectifier potassium currents in mammalian skeletal muscle fibres

    PubMed Central

    DiFranco, Marino; Yu, Carl; Quiñonez, Marbella; Vergara, Julio L

    2015-01-01

    Inward rectifying potassium (Kir) channels play a central role in maintaining the resting membrane potential of skeletal muscle fibres. Nevertheless their role has been poorly studied in mammalian muscles. Immunohistochemical and transgenic expression were used to assess the molecular identity and subcellular localization of Kir channel isoforms. We found that Kir2.1 and Kir2.2 channels were targeted to both the surface andthe transverse tubular system membrane (TTS) compartments and that both isoforms can be overexpressed up to 3-fold 2 weeks after transfection. Inward rectifying currents (IKir) had the canonical features of quasi-instantaneous activation, strong inward rectification, depended on the external [K+], and could be blocked by Ba2+ or Rb+. In addition, IKir records show notable decays during large 100 ms hyperpolarizing pulses. Most of these properties were recapitulated by model simulations of the electrical properties of the muscle fibre as long as Kir channels were assumed to be present in the TTS. The model also simultaneously predicted the characteristics of membrane potential changes of the TTS, as reported optically by a fluorescent potentiometric dye. The activation of IKir by large hyperpolarizations resulted in significant attenuation of the optical signals with respect to the expectation for equal magnitude depolarizations; blocking IKir with Ba2+ (or Rb+) eliminated this attenuation. The experimental data, including the kinetic properties of IKir and TTS voltage records, and the voltage dependence of peak IKir, while measured at widely dissimilar bulk [K+] (96 and 24 mm), were closely predicted by assuming Kir permeability (PKir) values of ∼5.5 × 10−6 cm s−1 and equal distribution of Kir channels at the surface and TTS membranes. The decay of IKir records and the simultaneous increase in TTS voltage changes were mostly explained by K+ depletion from the TTS lumen. Most importantly, aside from allowing an accurate estimation of

  8. STEREOLOGICAL ANALYSIS OF MAMMALIAN SKELETAL MUSCLE

    PubMed Central

    Eisenberg, Brenda R.; Kuda, Aileen M.; Peter, James B.

    1974-01-01

    A quantitative analysis of the volumes, surface areas, and dimensions of the ultrastructural components in the soleus muscle fibers of the guinea pig was made by using point counting methods of stereology. Muscle fibers have structural orientation (anisotropy) and have spatial gradients of the structures within the fiber; therefore the standard stereological methods were modified where necessary. The entire analysis was repeated at two section orientations to test the modifications and identical results obtained from both. The volume of lipid droplets was 0.20 ± 0.06% (mean ± standard error, n = 5 animals) and the nuclei volume was 0.86 ± 0.20% of the fiber volume. The total mitochondrial volume was 4.85 ± 0.66% of the fiber volume with about one-third being found in an annulus within 1 µm of the sarcolemma. The mitochondrial volume in the remaining core of the fiber was 3.6 ± 0.4%. The T system has a volume of 0.14 ± 0.01% and a surface area of 0.064 ± 0.005 µm2/µm3 of the fiber volume. The surface area of the sarcolemma is 0.116 ± 0.013 µm2/µm3 which is twice the T system surface area. The volume of the entire sarcoplasmic reticulum is 3.52 ± 0.33% and the surface area is 0.97 ± 0.09 µm2/µm3. The sarcoplasmic reticulum is composed of the terminal cisternae whose volume is 1.04 ± 0.19% and surface area is 0.24 ± 0.05 µm2/µm3. The tubules of the sarcoplasmic reticulum in the I band and A band have volumes of 1.97 ± 0.24% and 0.51 ± 0.08%, and the surface areas of the I and A band reticulum are 0.56 ± 0.07 µm2/µm3 and 0.16 ± 0.04 µm2/µm3, respectively. The Z line width, myofibril and fiber diameters were measured. PMID:4824293

  9. Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

    ERIC Educational Resources Information Center

    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

  10. An allometric analysis of the number of muscle spindles in mammalian skeletal muscles.

    PubMed

    Banks, R W

    2006-06-01

    An allometric analysis of the number of muscle spindles in relation to muscle mass in mammalian (mouse, rat, guinea-pig, cat, human) skeletal muscles is presented. It is shown that the trend to increasing number as muscle mass increases follows an isometric (length) relationship between species, whereas within a species, at least for the only essentially complete sample (human), the number of spindles scales, on average, with the square root rather than the cube root of muscle mass. An attempt is made to reconcile these apparently discrepant relationships. Use of the widely accepted spindle density (number of spindles g(-1) of muscle) as a measure of relative abundance of spindles in different muscles is shown to be grossly misleading. It is replaced with the residuals of the linear regression of ln spindle number against ln muscle mass. Significant differences in relative spindle abundance as measured by residuals were found between regional groups of muscles: the greatest abundance is in axial muscles, including those concerned with head position, whereas the least is in muscles of the shoulder girdle. No differences were found between large and small muscles operating in parallel, or between antigravity and non-antigravity muscles. For proximal vs. distal muscles, spindles were significantly less abundant in the hand than the arm, but there was no difference between the foot and the leg.

  11. Immunological studies on the structure and function of the nicotinic acetylcholine receptor in mammalian muscle

    SciTech Connect

    Gu, Y.

    1989-01-01

    The specificity of the antibodies in the serum of a patient with myasthenia gravis for a the {alpha}-bungarotoxin binding sites of the acetylcholine receptor (AChR) was examined using AChRs in the C2 mouse muscle cell line as a model. The antibodies were shown to be specific for one of the two toxin-binding sites. The effect of the antibodies in this myasthenic serum on the functional response of the receptor to cholinergic agonists was also examined using carbamylcholine-induced {sup 22}Na uptake into C2 myotubes as a measured of the receptor function. Antibodies specific for the {gamma}, {delta}, and {epsilon} subunit, respectively, of mammalian muscle AChRs were developed using subunit-specific synthetic peptides as antigens. Using these antibodies and monoclonal antibodies for other subunits as probes, I have identified four ({alpha}, {beta}, {gamma}, and {delta}) subunits of mammalian muscle AChRs on immunoblots. When AChRs from embryonic, neonatal, normal and denervated adult muscles were compared on immunoblots, the {alpha}, {beta}, and {delta} subunits were identical in all four receptor preparations, with or without endoglycosidase digestion. The spatial and temporal distribution of the {gamma}- and {epsilon}- AChRs in developing and in denervated muscles corresponds to the distribution of AChRs with slow and fast channels, respectively, and that the development changes in the channel properties of the receptor arise from a change in the subunit composition of the receptor, in which the {gamma} is replaced by {epsilon}.

  12. Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later

    PubMed Central

    Bond, Allison M.; Ming, Guo-li; Song, Hongjun

    2015-01-01

    Summary Adult somatic stem cells in various organs maintain homeostatic tissue regeneration and enhance plasticity. Since its initial discovery five decades ago, investigations of adult neurogenesis and neural stem cells have led to an established and expanding field that has significantly influenced many facets of neuroscience, developmental biology and regenerative medicine. Here we review recent progress and focus on questions related to adult mammalian neural stem cells that also apply to other somatic stem cells. We further discuss emerging topics that are guiding the field toward better understanding adult neural stem cells and ultimately applying these principles to improve human health. PMID:26431181

  13. Control of Cell Survival in Adult Mammalian Neurogenesis.

    PubMed

    Kuhn, H Georg

    2015-10-28

    The fact that continuous proliferation of stem cells and progenitors, as well as the production of new neurons, occurs in the adult mammalian central nervous system (CNS) raises several basic questions concerning the number of neurons required in a particular system. Can we observe continued growth of brain regions that sustain neurogenesis? Or does an elimination mechanism exist to maintain a constant number of cells? If so, are old neurons replaced, or are the new neurons competing for limited network access among each other? What signals support their survival and integration and what factors are responsible for their elimination? This review will address these and other questions regarding regulatory mechanisms that control cell-death and cell-survival mechanisms during neurogenesis in the intact adult mammalian brain.

  14. The role of olfactory stimulus in adult mammalian neurogenesis.

    PubMed

    Arisi, Gabriel M; Foresti, Maira L; Mukherjee, Sanjib; Shapiro, Lee A

    2012-02-14

    Neurogenesis occurs in the adult mammalian brain in discrete regions related to olfactory sensory signaling and integration. The olfactory receptor cell population is in constant turn-over through local progenitor cells. Also, newborn neurons are added to the olfactory bulbs through a major migratory route from the subventricular zone, the rostral migratory stream. The olfactory bulbs project to different brain structures, including: piriform cortex, amygdala, entorhinal cortex, striatum and hippocampus. These structures play important roles in odor identification, feeding behavior, social interactions, reproductive behavior, behavioral reinforcement, emotional responses, learning and memory. In all of these regions neurogenesis has been described in normal and in manipulated mammalian brain. These data are reviewed in the context of a sensory-behavioral hypothesis on adult neurogenesis that olfactory input modulates neurogenesis in many different regions of the brain.

  15. Differentiation of mammalian skeletal muscle cells cultured on microcarrier beads in a rotating cell culture system

    NASA Technical Reports Server (NTRS)

    Torgan, C. E.; Burge, S. S.; Collinsworth, A. M.; Truskey, G. A.; Kraus, W. E.

    2000-01-01

    The growth and repair of adult skeletal muscle are due in part to activation of muscle precursor cells, commonly known as satellite cells or myoblasts. These cells are responsive to a variety of environmental cues, including mechanical stimuli. The overall goal of the research is to examine the role of mechanical signalling mechanisms in muscle growth and plasticity through utilisation of cell culture systems where other potential signalling pathways (i.e. chemical and electrical stimuli) are controlled. To explore the effects of decreased mechanical loading on muscle differentiation, mammalian myoblasts are cultured in a bioreactor (rotating cell culture system), a model that has been utilised to simulate microgravity. C2C12 murine myoblasts are cultured on microcarrier beads in a bioreactor and followed throughout differentiation as they form a network of multinucleated myotubes. In comparison with three-dimensional control cultures that consist of myoblasts cultured on microcarrier beads in teflon bags, myoblasts cultured in the bioreactor exhibit an attenuation in differentiation. This is demonstrated by reduced immunohistochemical staining for myogenin and alpha-actinin. Western analysis shows a decrease, in bioreactor cultures compared with control cultures, in levels of the contractile proteins myosin (47% decrease, p < 0.01) and tropomyosin (63% decrease, p < 0.01). Hydrodynamic measurements indicate that the decrease in differentiation may be due, at least in part, to fluid stresses acting on the myotubes. In addition, constraints on aggregate size imposed by the action of fluid forces in the bioreactor affect differentiation. These results may have implications for muscle growth and repair during spaceflight.

  16. Epigenetic choreographers of neurogenesis in the adult mammalian brain

    PubMed Central

    Ma, Dengke K; Marchetto, Maria Carolina; Guo, Junjie U; Ming, Guo-li; Gage, Fred H; Song, Hongjun

    2012-01-01

    Epigenetic mechanisms regulate cell differentiation during embryonic development and also serve as important interfaces between genes and the environment in adulthood. Neurogenesis in adults, which generates functional neural cell types from adult neural stem cells, is dynamically regulated by both intrinsic state-specific cell differentiation cues and extrinsic neural niche signals. Epigenetic regulation by DNA and histone modifiers, non-coding RNAs and other self-sustained mechanisms can lead to relatively long-lasting biological effects and maintain functional neurogenesis throughout life in discrete regions of the mammalian brain. Here, we review recent evidence that epigenetic mechanisms carry out diverse roles in regulating specific aspects of adult neurogenesis and highlight the implications of such epigenetic regulation for neural plasticity and disorders. PMID:20975758

  17. Adult neurogenesis in the mammalian hippocampus: Why the dentate gyrus?

    PubMed Central

    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity after the perinatal period suggests that unique aspects of the structure and function of DG and olfactory bulb circuits allow them to benefit from the adult generation of neurons. In this review, we consider the distinctive features of the DG that may account for it being able to profit from this singular form of neural plasticity. Approaches to the problem of neurogenesis are grouped as “bottom-up,” where the phenotype of adult-born granule cells is contrasted to that of mature developmentally born granule cells, and “top-down,” where the impact of altering the amount of neurogenesis on behavior is examined. We end by considering the primary implications of these two approaches and future directions. PMID:24255101

  18. Satellite-like cells contribute to pax7-dependent skeletal muscle repair in adult zebrafish.

    PubMed

    Berberoglu, Michael A; Gallagher, Thomas L; Morrow, Zachary T; Talbot, Jared C; Hromowyk, Kimberly J; Tenente, Inês M; Langenau, David M; Amacher, Sharon L

    2017-04-15

    Satellite cells, also known as muscle stem cells, are responsible for skeletal muscle growth and repair in mammals. Pax7 and Pax3 transcription factors are established satellite cell markers required for muscle development and regeneration, and there is great interest in identifying additional factors that regulate satellite cell proliferation, differentiation, and/or skeletal muscle regeneration. Due to the powerful regenerative capacity of many zebrafish tissues, even in adults, we are exploring the regenerative potential of adult zebrafish skeletal muscle. Here, we show that adult zebrafish skeletal muscle contains cells similar to mammalian satellite cells. Adult zebrafish satellite-like cells have dense heterochromatin, express Pax7 and Pax3, proliferate in response to injury, and show peak myogenic responses 4-5 days post-injury (dpi). Furthermore, using a pax7a-driven GFP reporter, we present evidence implicating satellite-like cells as a possible source of new muscle. In lieu of central nucleation, which distinguishes regenerating myofibers in mammals, we describe several characteristics that robustly identify newly-forming myofibers from surrounding fibers in injured adult zebrafish muscle. These characteristics include partially overlapping expression in satellite-like cells and regenerating myofibers of two RNA-binding proteins Rbfox2 and Rbfoxl1, known to regulate embryonic muscle development and function. Finally, by analyzing pax7a; pax7b double mutant zebrafish, we show that Pax7 is required for adult skeletal muscle repair, as it is in the mouse.

  19. Halothane cooling contractures of skinned mammalian muscle fibers.

    PubMed

    Sudo, R T; Zapata-Sudo, G; Suarez-Kurtz, G

    1990-11-01

    The effects of halothane or cooling on Ca2(+)-activated tensions and on the uptake and release of Ca2+ by the sarcoplasmic reticulum were investigated in chemically skinned fibers of the extensor digitorum longus muscle of adult rabbits. At 22 degrees C, halothane (greater than 0.46 mM) induced Ca2+ release from the SR of Ca2(+)-loaded skinned fibers that resulted in transient tensions. Higher concentrations of halothane (greater than 4.65 mM) reduced the steady-state accumulation of Ca2+ in the SR at 22 degrees C. Cooling (to less than 10 degrees C) elicited transient contractures (cooling-induced contractures [CC]) in Ca2(+)-loaded skinned fibers, despite the fact that the tensions elicited by adding Ca2+ to the bath were depressed at these low temperatures. The skinned fibers did not develop CCs at 12-16 degrees C. Halothane cooling contractures could be elicited at these temperatures by exposing the fibers to halothane concentrations that failed to elicit Ca2+ release at 22 degrees C. The halothane cooling contractures were blocked by procaine but not by lidocaine. It was concluded that these contractures resulted from a synergistic interaction between halothane and cooling that stimulates Ca2+ release from, and reduces Ca2+ uptake by, the sarcoplasmic reticulum.

  20. Transcriptional activation of muscle atrophy promotes cardiac muscle remodeling during mammalian hibernation

    PubMed Central

    Zhang, Yichi; Aguilar, Oscar A.

    2016-01-01

    Background. Mammalian hibernation in thirteen-lined ground squirrels (Ictidomys tridecemlineatus) is characterized by dramatic changes on a physiological and molecular level. During hibernation, mammalian hearts show a propensity to hypertrophy due to the need for increasing contractility to pump colder and more viscous blood. While cardiac hypertrophy is quite often a process characterized by decompensation, the ground squirrel studied is an excellent model of cardiac plasticity and cardioprotection under conditions of hypothermia and ischemia. The forkhead box O (Foxo) family of proteins and myogenin (MyoG) are transcription factors that control protein degradation and muscle atrophy by regulating the expression of the E3 ubiquitin ligases, MAFbx and MuRF1. These ligases are part of the ubiquitin proteasome system by transferring ubiquitin to proteins and targeting these proteins for degradation. Regulation of Foxo1 and 3a occurs through phosphorylation at different residues. The threonine-24 (Thr-24) and serine-319 (Ser-319) residues on Foxo1, and the Thr-32 residue on Foxo3a are phosphorylated by Akt, leading to cytoplasmic localization of Foxo. We propose that the described mechanism contributes to the changes taking place in cardiac muscle throughout hibernation. Methods. Total and phosphorylated protein levels of Foxo1 and Foxo3a, as well as total protein levels of MyoG, MAFbx, and MuRF1, were studied using immunoblotting. Results. Immunoblotting results demonstrated upregulations in Foxo1 and Foxo3a total protein levels (1.3- and 4.5-fold increases relative to euthermic control, for Foxo1 and 3a respectively) during late torpor, and protein levels remained elevated throughout the rest of torpor and at interbout arousal. We also observed decreases in inactive, phosphorylated Foxo1 and 3a proteins during throughout torpor, where levels of p-Foxo1 Ser319 and Thr24, as well as p-Foxo3a Thr32 decreased by at least 45% throughout torpor. MyoG was upregulated only

  1. Molecular basis of the differential sensitivity of nematode and mammalian muscle to the anthelmintic agent levamisole.

    PubMed

    Rayes, Diego; De Rosa, María José; Bartos, Mariana; Bouzat, Cecilia

    2004-08-27

    Levamisole is an anthelmintic agent that exerts its therapeutic effect by acting as a full agonist of the nicotinic receptor (AChR) of nematode muscle. Its action at the mammalian muscle AChR has not been elucidated to date despite its wide use as an anthelmintic in humans and cattle. By single channel and macroscopic current recordings, we investigated the interaction of levamisole with the mammalian muscle AChR. Levamisole activates mammalian AChRs. However, single channel openings are briefer than those activated by acetylcholine (ACh) and do not appear in clusters at high concentrations. The peak current induced by levamisole is about 3% that activated by ACh. Thus, the anthelmintic acts as a weak agonist of the mammalian AChR. Levamisole also produces open channel blockade of the AChR. The apparent affinity for block (190 microm at -70 mV) is similar to that of the nematode AChR, suggesting that differences in channel activation kinetics govern the different sensitivity of nematode and mammalian muscle to anthelmintics. To identify the structural basis of this different sensitivity, we performed mutagenesis targeting residues in the alpha subunit that differ between vertebrates and nematodes. The replacement of the conserved alphaGly-153 with the homologous glutamic acid of nematode AChR significantly increases the efficacy of levamisole to activate channels. Channel activity takes place in clusters having two different kinetic modes. The kinetics of the high open probability mode are almost identical when the agonist is ACh or levamisole. It is concluded that alphaGly-153 is involved in the low efficacy of levamisole to activate mammalian muscle AChRs.

  2. Heat production and metabolism during the contraction of mammalian skeletal muscle.

    PubMed

    Kretzschmar, K M

    1975-01-01

    Methods are described whereby initial processes of muscular contraction may be investigated in a mammalian preparation, the soleus muscle of the rat. Conditions are chosen so that recovery is avoided. An isometric tetanus is investigated and an energy balance sheet is drawn up. It is found that there is more heat evolved than can be accounted for in terms of measured chemical reaction. This discrepancy is discussed with reference to the similar results that have been obtained using frog muscle.

  3. Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain.

    PubMed

    Feliciano, David M; Bordey, Angélique; Bonfanti, Luca

    2015-09-18

    Two decades after the discovery that neural stem cells (NSCs) populate some regions of the mammalian central nervous system (CNS), deep knowledge has been accumulated on their capacity to generate new neurons in the adult brain. This constitutive adult neurogenesis occurs throughout life primarily within remnants of the embryonic germinal layers known as "neurogenic sites." Nevertheless, some processes of neurogliogenesis also occur in the CNS parenchyma commonly considered as "nonneurogenic." This "noncanonical" cell genesis has been the object of many claims, some of which turned out to be not true. Indeed, it is often an "incomplete" process as to its final outcome, heterogeneous by several measures, including regional location, progenitor identity, and fate of the progeny. These aspects also strictly depend on the animal species, suggesting that persistent neurogenic processes have uniquely adapted to the brain anatomy of different mammals. Whereas some examples of noncanonical neurogenesis are strictly parenchymal, others also show stem cell niche-like features and a strong link with the ventricular cavities. This work will review results obtained in a research field that expanded from classic neurogenesis studies involving a variety of areas of the CNS outside of the subventricular zone (SVZ) and subgranular zone (SGZ). It will be highlighted how knowledge concerning noncanonical neurogenic areas is still incomplete owing to its regional and species-specific heterogeneity, and to objective difficulties still hampering its full identification and characterization.

  4. Skeletal muscle mass and composition during mammalian hibernation.

    PubMed

    Cotton, Clark J

    2016-01-01

    Hibernation is characterized by prolonged periods of inactivity with concomitantly low nutrient intake, conditions that would typically result in muscle atrophy combined with a loss of oxidative fibers. Yet, hibernators consistently emerge from winter with very little atrophy, frequently accompanied by a slight shift in fiber ratios to more oxidative fiber types. Preservation of muscle morphology is combined with down-regulation of glycolytic pathways and increased reliance on lipid metabolism instead. Furthermore, while rates of protein synthesis are reduced during hibernation, balance is maintained by correspondingly low rates of protein degradation. Proposed mechanisms include a number of signaling pathways and transcription factors that lead to increased oxidative fiber expression, enhanced protein synthesis and reduced protein degradation, ultimately resulting in minimal loss of skeletal muscle protein and oxidative capacity. The functional significance of these outcomes is maintenance of skeletal muscle strength and fatigue resistance, which enables hibernating animals to resume active behaviors such as predator avoidance, foraging and mating immediately following terminal arousal in the spring.

  5. Multifaceted role of insulin-like growth factors and mammalian target of rapamycin in skeletal muscle.

    PubMed

    Frost, Robert A; Lang, Charles H

    2012-06-01

    This review describes the current literature on the interaction between insulin-like growth factors, endocrine hormones, and branched-chain amino acids on muscle physiology in healthy young individuals and during select pathologic conditions. Emphasis is placed on the mechanism by which physical and hormonal signals are transduced at the cellular level to either grow or atrophy skeletal muscle. The key role of the mammalian target of rapamycin and its ability to respond to hypertrophic and atrophic signals informs our understanding how a combination of physical, nutritional, and pharmacologic therapies may be used in tandem to prevent or ameliorate reductions in muscle mass.

  6. Effect of extracellular osmolality on cell volume and resting metabolism in mammalian skeletal muscle.

    PubMed

    Antolic, AnaMaria; Harrison, Rosemarie; Farlinger, Chris; Cermak, Naomi M; Peters, Sandra J; LeBlanc, Paul; Roy, Brian D

    2007-05-01

    The purpose of the present investigation was to establish an in vitro mammalian skeletal muscle model to study acute alterations in resting skeletal muscle cell volume. Isolated, whole muscles [soleus and extensor digitorum longus (EDL)] were dissected from Long-Evans rats and incubated for 60 min in Sigma medium 199 (1 g of resting tension, bubbled with 95% O(2)-5% O(2), 30 +/- 2 degrees C, and pH 7.4). Medium osmolality was altered to simulate hyposmotic (190 +/- 10 mmol/kg) or hyperosmotic conditions (400 +/- 10 mmol/kg), whereas an isosmotic condition (290 +/- 10 mmol/kg) served as a control. After incubation, relative water content of the muscle decreased with hyperosmotic and increased with hyposmotic condition in both muscle types (P < 0.05). The cross-sectional area of soleus type I and type II fibers increased (P < 0.05) in hyposmotic, whereas hyperosmotic exposure led to no detectable changes. The EDL type II fiber area decreased in the hyperosmotic condition and increased after hyposmotic exposure, whereas no change was observed in EDL type I fibers. Furthermore, exposure to the hyperosmotic condition in both muscle types resulted in decreased muscle ATP and phosphocreatine (P < 0.05) contents and increased creatine and lactate contents (P < 0.05) compared with control and hyposmotic conditions. This isolated skeletal muscle model proved viable and demonstrated that altering extracellular osmolality could cause acute alterations in muscle water content and resting muscle metabolism.

  7. Force-frequency relationship and potentiation in mammalian skeletal muscle.

    PubMed

    MacIntosh, B R; Willis, J C

    2000-06-01

    Repetitive activation of a skeletal muscle results in potentiation of the twitch contractile response. Incompletely fused tetanic contractions similar to those evoked by voluntary activation may also be potentiated by prior activity. We aimed to investigate the role of stimulation frequency on the enhancement of unfused isometric contractions in rat medial gastrocnemius muscles in situ. Muscles set at optimal length were stimulated via the sciatic nerve with 50-micros duration supramaximal pulses. Trials consisted of 8 s of repetitive trains [5 pulses (quintuplets) 2 times per second or 2 pulses (doublets) 5 times per second] at 20, 40, 50, 60, 70, and 80 Hz. These stimulation frequencies represent a range over which voluntary activation would be expected to occur. When the frequency of stimulation was 20, 50, or 70 Hz, the peak active force (highest tension during a contraction - rest tension) of doublet contractions increased from 2.2 +/- 0.2, 4.1 +/- 0.4, and 4.3 +/- 0.5 to 3.1 +/- 0.3, 5.6 +/- 0.4, and 6.1 +/- 0.7 N, respectively. Corresponding measurements for quintuplet contractions increased from 2.2 +/- 0.2, 6.1 +/- 0.5, and 8.7 +/- 0.7 to 3.2 +/- 0.3, 7.3 +/- 0.6, and 9.0 +/- 0.7 N, respectively. Initial peak active force values were 27 +/- 1 and 61.5 +/- 5% of the maximal (tetanic) force for doublet and quintuplet contractions, respectively, at 80 Hz. With doublets, peak active force increased at all stimulation frequencies. With quintuplets, peak active force increased significantly for frequencies up to 60 Hz. Twitch enhancement at the end of the 8 s of repetitive stimulation was the same regardless of the pattern of stimulation during the 8 s, and twitch peak active force returned to prestimulation values by 5 min. These experiments confirm that activity-dependent potentiation is evident during repeated, incompletely fused tetanic contractions over a broad range of frequencies. This observation suggests that, during voluntary motor unit recruitment

  8. An active learning mammalian skeletal muscle lab demonstrating contractile and kinetic properties of fast- and slow-twitch muscle.

    PubMed

    Head, S I; Arber, M B

    2013-12-01

    The fact that humans possess fast- and slow-twitch muscle in the ratio of ∼50% has profound implications for designing exercise training strategies for power and endurance activities. With the growth of exercise and sport science courses, we have seen the need to develop an undergraduate student laboratory that demonstrates the basic properties of fast- and slow-twitch mammalian skeletal muscle. This laboratory illustrates the major differences in contractile properties and fatigue profiles exhibited by the two muscle types. Students compare and contrast twitch kinetics, fused tetanus characteristics, force-frequency relationships, and fatigue properties of fast- and slow-twitch muscles. Examples of results collected by students during class are used to illustrate the type of data collected and analysis performed. During the laboratory, students are encouraged to connect factual information from their skeletal muscle lectures to their laboratory findings. This enables student learning in an active fashion; in particular, the isolated muscle preparation demonstrates that much of what makes muscle fast or slow is myogenic and not the product of the nervous or circulatory systems. This has far-reaching implications for motor control and exercise behavior and therefore is a crucial element in exercise science, with its focus on power and endurance sport activities. To measure student satisfaction with this active learning technique, a questionnaire was administered after the laboratory; 96% of the comments were positive in their support of active versus passive learning strategies.

  9. MED12 mutations occurring in benign and malignant mammalian smooth muscle tumors.

    PubMed

    Markowski, Dominique Nadine; Huhle, Sonja; Nimzyk, Rolf; Stenman, Göran; Löning, Thomas; Bullerdiek, Jörn

    2013-03-01

    Mutations of the mediator subcomplex 12 gene (MED12) recently have been described in a large group of uterine leiomyomas (UL) but only in a single malignant uterine smooth muscle tumor. To further address the occurrence of fibroid-type MED12 mutations in smooth muscle tumors, we have analyzed samples from 34 leiomyosarcomas (LMS), 21 UL, two extrauterine leiomyomas (EL), and 10 canine genital leiomyomas for the presence of MED12 mutations of the UL-type. Interestingly, besides UL MED12 mutations were found in one uterine LMS, one EL, and two canine vaginal leiomyomas. The results confirm the occurrence of fibroid-type MED12 mutations in malignant uterine smooth muscle tumors thus suggesting a rare but existing leiomyoma-LMS sequence. In addition, for the first time MED12 mutations are reported in smooth muscle tumors in a non-primate mammalian species.

  10. Development of the diaphragm, a skeletal muscle essential for mammalian respiration

    PubMed Central

    Merrell, Allyson J.; Kardon, Gabrielle

    2013-01-01

    The mammalian diaphragm muscle is essential for respiration, and thus it is among the most critical of the skeletal muscles in the human body. Defects in diaphragm development, leading to congenital diaphragmatic hernias (CDH), are common birth defects and result in severe morbidity or mortality. Given its functional importance and the frequency of congenital defects, an understanding of diaphragm development normally and during herniation is important. We review the current knowledge of the embryological origins of the diaphragm, diaphragm development and morphogenesis, and the genetic and developmental etiology of diaphragm birth defects. PMID:23586979

  11. Preliminary evidence for a postsynaptic action of beta-bungarotoxin in mammalian skeletal muscle

    NASA Technical Reports Server (NTRS)

    Storella, R. J.; Schouchoff, A. L.; Fujii, M.; Hill, J.; Fletcher, J. E.; Jiang, M. S.; Smith, L. A.

    1992-01-01

    Two hours after treatment with beta-bungarotoxin (0.34-0.4 microM), when there was complete neuromuscular block, the peak contracture response to 50 microM succinylcholine was significantly reduced by about 35% in the mouse phrenic nerve-diaphragm preparation. Additionally, significant phospholipase A2 activity was detected on primary cell cultures from skeletal muscle which were incubated for 2 hr with concentrations of beta-bungarotoxin greater than or equal to 0.1 microM. Thus, beta-bungarotoxin appears to have pharmacologically and biochemically detectable postsynaptic actions in mammalian muscle systems.

  12. Electrical constants of trabecular muscle from mammalian heart.

    PubMed

    Weidmann, S

    1970-11-01

    1. The passive electrical properties of muscle bundles obtained from the right ventricle of sheep or calf hearts were determined. Preparations were kept in silicon oil; through extracellular electrodes constant current pulses were made to flow between the ends of the bundles.2. Using micro-electrodes for potential recording, the following data were obtained: (i) a space constant of 880 mu; (ii) a membrane time constant of 4.4 msec; (iii) a ratio of intra-to-extracellular longitudinal resistance of 3.5: 1; (iv) a conduction velocity of 0.75 m/sec.3. The intracellular specific resistance (R(i)) in the longitudinal direction was 470Omega cm, corresponding to 3 times R(i) of Purkinje fibres or 9 times the specific resistance of Tyrode solution.4. A calculation of specific membrane resistance (R(m)) and capacity (C(m)) was up against uncertainties in estimating the surface area. Taking morphological data as obtained by light microscopy, R(m) works out at 9100Omega cm(2), C(m) 0.81 muF/cm(2). Electron micrographs suggest that the true surface membrane might be either larger (T-tubules) or smaller (tight junctions between parallel fibres) than the surface area as seen by the light microscope.5. The apparently small value of C(m) seems to indicate that the flow of current between ;outside' and ;inside' is restricted to only a fraction of the fibre surface, while a considerable part of the contact area between parallel fibres is of the low-resistance type. This would provide for functional connexions not only at the level of intercalated disks, but also along parallel-running fibres.

  13. Amiloride-sensitive channels are a major contributor to mechanotransduction in mammalian muscle spindles

    PubMed Central

    Simon, Anna; Shenton, Fiona; Hunter, Irene; Banks, Robert W; Bewick, Guy S

    2010-01-01

    We investigated whether channels of the epithelial sodium/amiloride-sensitive degenerin (ENaC/DEG) family are a major contributor to mechanosensory transduction in primary mechanosensory afferents, using adult rat muscle spindles as a model system. Stretch-evoked afferent discharge was reduced in a dose-dependent manner by amiloride and three analogues – benzamil, 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and hexamethyleneamiloride (HMA), reaching ≥85% inhibition at 1 mm. Moreover, firing was slightly but significantly increased by ENaC δ subunit agonists (icilin and capsazepine). HMA's profile of effects was distinct from that of the other drugs. Amiloride, benzamil and EIPA significantly decreased firing (P < 0.01 each) at 1 μm, while 10 μm HMA was required for highly significant inhibition (P < 0.0001). Conversely, amiloride, benzamil and EIPA rarely blocked firing entirely at 1 mm, whereas 1 mm HMA blocked 12 of 16 preparations. This pharmacology suggests low-affinity ENaCs are the important spindle mechanotransducer. In agreement with this, immunoreactivity to ENaC α, β and γ subunits was detected both by Western blot and immunocytochemistry. Immunofluorescence intensity ratios for ENaC α, β or γ relative to the vesicle marker synaptophysin in the same spindle all significantly exceeded controls (P < 0.001). Ratios for the related brain sodium channel ASIC2 (BNaC1α) were also highly significantly greater (P < 0.005). Analysis of confocal images showed strong colocalisation within the terminal of ENaC/ASIC2 subunits and synaptophysin. This study implicates ENaC and ASIC2 in mammalian mechanotransduction. Moreover, within the terminals they colocalise with synaptophysin, a marker for the synaptic-like vesicles which regulate afferent excitability in these mechanosensitive endings. PMID:19917568

  14. Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models

    PubMed Central

    Demontis, Fabio; Piccirillo, Rosanna; Goldberg, Alfred L.; Perrimon, Norbert

    2013-01-01

    A characteristic feature of aged humans and other mammals is the debilitating, progressive loss of skeletal muscle function and mass that is known as sarcopenia. Age-related muscle dysfunction occurs to an even greater extent during the relatively short lifespan of the fruit fly Drosophila melanogaster. Studies in model organisms indicate that sarcopenia is driven by a combination of muscle tissue extrinsic and intrinsic factors, and that it fundamentally differs from the rapid atrophy of muscles observed following disuse and fasting. Extrinsic changes in innervation, stem cell function and endocrine regulation of muscle homeostasis contribute to muscle aging. In addition, organelle dysfunction and compromised protein homeostasis are among the primary intrinsic causes. Some of these age-related changes can in turn contribute to the induction of compensatory stress responses that have a protective role during muscle aging. In this Review, we outline how studies in Drosophila and mammalian model organisms can each provide distinct advantages to facilitate the understanding of this complex multifactorial condition and how they can be used to identify suitable therapies. PMID:24092876

  15. Two novel/ancient myosins in mammalian skeletal muscles: MYH14/7b and MYH15 are expressed in extraocular muscles and muscle spindles

    PubMed Central

    Rossi, Alberto C; Mammucari, Cristina; Argentini, Carla; Reggiani, Carlo; Schiaffino, Stefano

    2010-01-01

    The mammalian genome contains three ancient sarcomeric myosin heavy chain (MYH) genes, MYH14/7b, MYH15 and MYH16, in addition to the two well characterized clusters of skeletal and cardiac MYHs. MYH16 is expressed in jaw muscles of carnivores; however the expression pattern of MYH14 and MYH15 is not known. MYH14 and MYH15 orthologues are present in frogs and birds, coding for chicken slow myosin 2 and ventricular MYH, respectively, whereas only MYH14 orthologues have been detected in fish. In all species the MYH14 gene contains a microRNA, miR-499. Here we report that in rat and mouse, MYH14 and miR-499 transcripts are detected in heart, slow muscles and extraocular (EO) muscles, whereas MYH15 transcripts are detected exclusively in EO muscles. However, MYH14 protein is detected only in a minor fibre population in EO muscles, corresponding to slow-tonic fibres, and in bag fibres of muscle spindles. MYH15 protein is present in most fibres of the orbital layer of EO muscles and in the extracapsular region of bag fibres. During development, MYH14 is expressed at low levels in skeletal muscles, heart and all EO muscle fibres but disappears from most fibres, except the slow-tonic fibres, after birth. In contrast, MYH15 is absent in embryonic and fetal muscles and is first detected after birth in the orbital layer of EO muscles. The identification of the expression pattern of MYH14 and MYH15 brings to completion the inventory of the MYH isoforms involved in sarcomeric architecture of skeletal muscles and provides an unambiguous molecular basis to study the contractile properties of slow-tonic fibres in mammals. PMID:19948655

  16. Numerical analysis of Ca2+ depletion in the transverse tubular system of mammalian muscle.

    PubMed Central

    Friedrich, O; Ehmer, T; Uttenweiler, D; Vogel, M; Barry, P H; Fink, R H

    2001-01-01

    Calcium currents were recorded in contracting and actively shortening mammalian muscle fibers. In order to characterize the influence of extracellular calcium concentration changes in the small unstirred lumina of the transverse tubular system (TTS) on the time course of the slow L-type calcium current (I(Ca)), we have combined experimental measurements of I(Ca) with quantitative numerical simulations of Ca2+ depletion. I(Ca) was recorded both in calcium-buffered and unbuffered external solutions using the two-microelectrode voltage clamp technique (2-MVC) on short murine toe muscle fibers. A simulation program based on a distributed TTS model was used to calculate the effect of ion depletion in the TTS. The experimental data obtained in a solution where ion depletion is suppressed by a high amount of a calcium buffering agent were used as input data for the simulation. The simulation output was then compared with experimental data from the same fiber obtained in unbuffered solution. Taking this approach, we could quantitatively show that the calculated Ca2+ depletion in the transverse tubular system of contracting mammalian muscle fibers significantly affects the time-dependent decline of Ca2+ currents. From our findings, we conclude that ion depletion in the tubular system may be one of the major effects for the I(Ca) decline measured in isotonic physiological solution under voltage clamp conditions. PMID:11325708

  17. Three-dimensional structure of the Z band in a normal mammalian skeletal muscle

    PubMed Central

    1996-01-01

    The three-dimensional structure of the vertebrate skeletal muscle Z band reflects its function as the muscle component essential for tension transmission between successive sarcomeres. We have investigated this structure as well as that of the nearby I band in a normal, unstimulated mammalian skeletal muscle by tomographic three- dimensional reconstruction from electron micrograph tilt series of sectioned tissue. The three-dimensional Z band structure consists of interdigitating axial filaments from opposite sarcomeres connected every 18 +/- 12 nm (mean +/- SD) to one to four cross-connecting Z- filaments are observed to meet the axial filaments in a fourfold symmetric arrangement. The substantial variation in the spacing between cross-connecting Z-filament to axial filament connection points suggests that the structure of the Z band is not determined solely by the arrangement of alpha-actinin to actin-binding sites along the axial filament. The cross-connecting filaments bind to or form a "relaxed interconnecting body" halfway between the axial filaments. This filamentous body is parallel to the Z band axial filaments and is observed to play an essential role in generating the small square lattice pattern seen in electron micrographs of unstimulated muscle cross sections. This structure is absent in cross section of the Z band from muscles fixed in rigor or in tetanus, suggesting that the Z band lattice must undergo dynamic rearrangement concomitant with crossbridge binding in the A band. PMID:8636232

  18. The Social Environment and Neurogenesis in the Adult Mammalian Brain

    PubMed Central

    Lieberwirth, Claudia; Wang, Zuoxin

    2012-01-01

    Adult neurogenesis – the formation of new neurons in adulthood – has been shown to be modulated by a variety of endogenous (e.g., trophic factors, neurotransmitters, and hormones) as well as exogenous (e.g., physical activity and environmental complexity) factors. Research on exogenous regulators of adult neurogenesis has focused primarily on the non-social environment. More recently, however, evidence has emerged suggesting that the social environment can also affect adult neurogenesis. The present review details the effects of adult–adult (e.g., mating and chemosensory interactions) and adult–offspring (e.g., gestation, parenthood, and exposure to offspring) interactions on adult neurogenesis. In addition, the effects of a stressful social environment (e.g., lack of social support and dominant–subordinate interactions) on adult neurogenesis are reviewed. The underlying hormonal mechanisms and potential functional significance of adult-generated neurons in mediating social behaviors are also discussed. PMID:22586385

  19. A myogenic factor from sea urchin embryos capable of programming muscle differentiation in mammalian cells.

    PubMed Central

    Venuti, J M; Goldberg, L; Chakraborty, T; Olson, E N; Klein, W H

    1991-01-01

    Using the basic helix-loop-helix domain of the myogenic factor myogenin as a probe, we identified a clone from a sea urchin cDNA library with considerable sequence similarity to the vertebrate myogenic factors. This cDNA, sea urchin myogenic factor 1 (SUM-1), transactivated a muscle creatine kinase-chloramphenicol acetyltransferase reporter gene in 10T1/2 fibroblasts to a level comparable to that of the vertebrate myogenic factors. In addition, bacterially expressed beta-galactosidase-SUM-1 fusion protein interacted directly with the kappa E-2 site in the muscle creatine kinase enhancer core as assayed by electrophoretic mobility shift assays. Stably transfected SUM-1 activated the muscle differentiation program and converted 10T1/2 cells from fibroblasts to myotubes. In sea urchin embryos, SUM-1 RNA was not detected before gastrulation. It accumulated to its highest levels during the prism stage when myoblasts were first detected by myosin immunostaining and then diminished as myocytes differentiated. SUM-1 protein was localized in secondary mesenchyme cells when they could first be identified as muscle cells by myosin immunostaining. These results implicate SUM-1 as a regulatory factor involved in the early decision of a pluripotent secondary mesenchyme cell to convert to a myogenic fate. SUM-1 is an example of an invertebrate myogenic factor that is capable of functioning in mammalian cells. Images PMID:2068103

  20. Thienylhydrazone derivative increases sarcoplasmic reticulum Ca2+ release in mammalian skeletal muscle.

    PubMed

    Zapata-Sudo, Gisele; Sudo, Roberto T; Maronas, Patricia A; Silva, Gisele L M; Moreira, Orlando R; Aguiar, Marli I S; Barreiro, Eliezer J

    2003-05-30

    3,4-Methylenedioxybenzoyl-2-thienylhydrazone (L-294) is a cardiac inotropic drug whose action is mediated by an increase in intracellular Ca(2+) concentration as a result of enhanced Ca(2+) accumulation in the sarcoplasmic reticulum. In the present study we tested whether this new thienylhydrazone derivative was effective in mammalian skeletal muscle. We investigated the effect of L-294 on the contractility of isolated skeletal muscle, on Ca(2+) uptake and release by sarcoplasmic reticulum in skinned fibers and in membrane vesicles. L-294 increased in a dose-dependent manner tension of isolated rat soleus muscle. In skinned type I fibers, L-294 induced tension and did not alter sarcoplasmic reticulum loading with Ca(2+). L-294 reduced the threshold Ca(2+) to induce Ca(2+) release and did not affect the ATP-dependent accumulation of Ca(2+) by sarcoplasmic reticulum vesicles. These results suggest that L-294 is an inotropic agent in skeletal muscle through an increase in the amount of Ca(2+) released from the sarcoplasmic reticulum.

  1. A new scenario of the evolutionary derivation of the mammalian diaphragm from shoulder muscles

    PubMed Central

    Hirasawa, Tatsuya; Kuratani, Shigeru

    2013-01-01

    The evolutionary origin of the diaphragm remains unclear, due to the lack of a comparable structure in other extant taxa. However, recent researches into the developmental mechanism of this structure have yielded new insights into its origin. Here we summarize current understanding regarding the development of the diaphragm, and present a possible scenario for the evolutionary acquisition of this uniquely mammalian structure. Recent developmental analyses indicate that the diaphragm and forelimb muscles are derived from a shared cell population during embryonic development. Therefore, the embryonic positions of forelimb muscle progenitors, which correspond to the position of the brachial plexus, likely played an important role in the evolution of the diaphragm. We surveyed the literature to reexamine the position of the brachial plexus among living amniotes and confirmed that the cervico-thoracic transition in ribs reflects the brachial plexus position. Using this osteological correlate, we concluded that the anterior borders of the brachial plexuses in the stem synapsids were positioned at the level of the fourth spinal nerve, suggesting that the forelimb buds were laid in close proximity of the infrahyoid muscles. The topology of the phrenic and suprascapular nerves of mammals is similar to that of subscapular and supracoracoid nerves, respectively, of the other amniotes, suggesting that the diaphragm evolved from a muscle positioned medial to the pectoral girdle (cf. subscapular muscle). We hypothesize that the diaphragm was acquired in two steps: first, forelimb muscle cells were incorporated into tissues to form a primitive diaphragm in the stem synapsid grade, and second, the diaphragm in cynodonts became entrapped in the region controlled by pulmonary development. PMID:23448284

  2. Muscle fatigue examined at different temperatures in experiments on intact mammalian (rat) muscle fibers

    PubMed Central

    Roots, H.; Ball, G.; Talbot-Ponsonby, J.; King, M.; McBeath, K.; Ranatunga, K. W.

    2009-01-01

    In experiments on small bundles of intact fibers from a rat fast muscle, in vitro, we examined the decline in force in repeated tetanic contractions; the aim was to characterize the effect of shortening and of temperature on the initial phase of muscle fatigue. Short tetanic contractions were elicited at a control repetition rate of 1/60 s, and fatigue was induced by raising the rate to 1/5 s for 2–3 min, both in isometric mode (no shortening) and in shortening mode, in which each tetanic contraction included a ramp shortening at a standard velocity. In experiments at 20°C (n = 12), the force decline during a fatigue run was 25% in the isometric mode but was significantly higher (35%) in the shortening mode. In experiments at different temperatures (10–30°C, n = 11), the tetanic frequency and duration were adjusted as appropriate, and for shortening mode, the velocity was adjusted for maximum power output. In isometric mode, fatigue of force was significantly less at 30°C (∼20%) than at 10°C (∼30%); the power output (force × velocity) was >10× higher at 30°C than at 10°C, and power decline during a fatigue run was less at 30°C (∼20–30%) than at 10°C (∼50%). The finding that the extent of fatigue is increased with shortening contractions and is lower at higher temperatures is consistent with the view that force depression by inorganic phosphate, which accumulates within fibers during activity, may be a primary cause of initial muscle fatigue. PMID:19057001

  3. An in vitro model of adult mammalian nerve repair.

    PubMed

    Vyas, Alka; Li, Zhaobo; Aspalter, Manuela; Feiner, Jeffrey; Hoke, Ahmet; Zhou, Chunhua; O'Daly, Andres; Abdullah, Madeel; Rohde, Charles; Brushart, Thomas M

    2010-05-01

    The role of pathway-derived growth factors in the support of peripheral axon regeneration remains elusive. Few appropriate knock-out mice are available, and gene silencing techniques are rarely 100% effective. To overcome these difficulties, we have developed an in vitro organotypic co-culture system that accurately models peripheral nerve repair in the adult mammal. Spinal cord sections from P4 mice that express YFP in their neurons are used to innervate segments of P4 peripheral nerve. This reconstructed ventral root is then transected and joined to a nerve graft. Growth of axons across the nerve repair and into the graft can be imaged repeatedly with fluorescence microscopy to define regeneration speed, and parent neurons can be labeled in retrograde fashion to identify contributing neurons. Nerve graft harvested from adult mice remains viable in culture by both morphologic and functional criteria. Motoneurons are supported with GDNF for the first week in culture, after which they survive axotomy, and are thus functionally adult. This platform can be modified by using motoneurons from any genetically modified mouse that can be bred to express XFP, by harvesting nerve graft from any source, or by treating the culture systemically with antibodies, growth factors, or pathway inhibitors. The regeneration environment is controlled to a degree not possible in vivo, and the use of experimental animals is reduced substantially. The flexibility and control offered by this technique should thus make it a useful tool for the study of regeneration biology.

  4. Potential for neural regeneration after neurotoxic injury in the adult mammalian retina

    NASA Astrophysics Data System (ADS)

    Ooto, Sotaro; Akagi, Tadamichi; Kageyama, Ryoichiro; Akita, Joe; Mandai, Michiko; Honda, Yoshihito; Takahashi, Masayo

    2004-09-01

    It has long been believed that the retina of mature mammals is incapable of regeneration. In this study, using the N-methyl-D-aspartate neurotoxicity model of adult rat retina, we observed that some Müller glial cells were stimulated to proliferate in response to a toxic injury and produce bipolar cells and rod photoreceptors. Although these newly produced neurons were limited in number, retinoic acid treatment promoted the number of regenerated bipolar cells. Moreover, misexpression of basic helix-loop-helix and homeobox genes promoted the induction of amacrine, horizontal, and rod photoreceptor specific phenotypes. These findings demonstrated that retinal neurons regenerated even in adult mammalian retina after toxic injury. Furthermore, we could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes. The Müller glial cells constitute a potential source for the regeneration of adult mammalian retina and can be a target for drug delivery and gene therapy in retinal degenerative diseases.

  5. Muscle organizers in Drosophila: the role of persistent larval fibers in adult flight muscle development

    NASA Technical Reports Server (NTRS)

    Farrell, E. R.; Fernandes, J.; Keshishian, H.

    1996-01-01

    In many organisms muscle formation depends on specialized cells that prefigure the pattern of the musculature and serve as templates for myoblast organization and fusion. These include muscle pioneers in insects and muscle organizing cells in leech. In Drosophila, muscle founder cells have been proposed to play a similar role in organizing larval muscle development during embryogenesis. During metamorphosis in Drosophila, following histolysis of most of the larval musculature, there is a second round of myogenesis that gives rise to the adult muscles. It is not known whether muscle founder cells organize the development of these muscles. However, in the thorax specific larval muscle fibers do not histolyze at the onset of metamorphosis, but instead serve as templates for the formation of a subset of adult muscles, the dorsal longitudinal flight muscles (DLMs). Because these persistent larval muscle fibers appear to be functioning in many respects like muscle founder cells, we investigated whether they were necessary for DLM development by using a microbeam laser to ablate them singly and in combination. We found that, in the absence of the larval muscle fibers, DLMs nonetheless develop. Our results show that the persistent larval muscle fibers are not required to initiate myoblast fusion, to determine DLM identity, to locate the DLMs in the thorax, or to specify the total DLM fiber volume. However, they are required to regulate the number of DLM fibers generated. Thus, while the persistent larval muscle fibers are not obligatory for DLM fiber formation and differentiation, they are necessary to ensure the development of the correct number of fibers.

  6. Myocyte Dedifferentiation Drives Extraocular Muscle Regeneration in Adult Zebrafish

    PubMed Central

    Saera-Vila, Alfonso; Kasprick, Daniel S.; Junttila, Tyler L.; Grzegorski, Steven J.; Louie, Ke'ale W.; Chiari, Estelle F.; Kish, Phillip E.; Kahana, Alon

    2015-01-01

    Purpose The purpose of this study was to characterize the injury response of extraocular muscles (EOMs) in adult zebrafish. Methods Adult zebrafish underwent lateral rectus (LR) muscle myectomy surgery to remove 50% of the muscle, followed by molecular and cellular characterization of the tissue response to the injury. Results Following myectomy, the LR muscle regenerated an anatomically correct and functional muscle within 7 to 10 days post injury (DPI). Following injury, the residual muscle stump was replaced by a mesenchymal cell population that lost cell polarity and expressed mesenchymal markers. Next, a robust proliferative burst repopulated the area of the regenerating muscle. Regenerating cells expressed myod, identifying them as myoblasts. However, both immunofluorescence and electron microscopy failed to identify classic Pax7-positive satellite cells in control or injured EOMs. Instead, some proliferating nuclei were noted to express mef2c at the very earliest point in the proliferative burst, suggesting myonuclear reprogramming and dedifferentiation. Bromodeoxyuridine (BrdU) labeling of regenerating cells followed by a second myectomy without repeat labeling resulted in a twice-regenerated muscle broadly populated by BrdU-labeled nuclei with minimal apparent dilution of the BrdU signal. A double-pulse experiment using BrdU and 5-ethynyl-2′-deoxyuridine (EdU) identified double-labeled nuclei, confirming the shared progenitor lineage. Rapid regeneration occurred despite a cell cycle length of 19.1 hours, whereas 72% of the regenerating muscle nuclei entered the cell cycle by 48 hours post injury (HPI). Dextran lineage tracing revealed that residual myocytes were responsible for muscle regeneration. Conclusions EOM regeneration in adult zebrafish occurs by dedifferentiation of residual myocytes involving a muscle-to-mesenchyme transition. A mechanistic understanding of myocyte reprogramming may facilitate novel approaches to the development of molecular

  7. Skeletal fiber types and spindle distribution in limb and jaw muscles of the adult and neonatal opossum, Monodelphis domestica.

    PubMed

    Sciote, J J; Rowlerson, A

    1998-08-01

    The South American opossum, Monodelphis domestica, is very immature at birth, and we wished to assess its potential for studies of jaw muscle development. Given the lack of prior information about any Monodelphis fiber types or spindles, our study aimed to identify for the first time fiber types in both adult and neonatal muscles and the location of spindles in the jaw muscles. Fiber types were identified in frozen sections of adult and 6-day-old jaw and limb muscles by using myosin ATPase and metabolic enzyme histochemistry and by immunostaining for myosin isoforms. The distribution of fiber types and muscle spindles throughout the jaw-closer muscles was identified by immunostaining of sections of methacarnoy-fixed, wax-embedded heads. Most muscles contained one slow (type I) and two fast fiber types (equivalent to types IIA and IIX), which were similar to those in eutherian muscle, and an additional (non-IIB) fast type. In jaw-closer muscles, the main extrafusal fiber type was IIM (characteristic of these muscles in some eutherians), and almost all spindles were concentrated in four restricted areas: one in masseter and three in temporalis. Six-day neonatal muscles were very immature, but future spindle-rich areas were revealed by immunostaining and corresponded in position to the adult areas. Extrafusal and spindle fiber types in Monodelphis share many similarities with eutherian mammalian muscle. This finding, along with the immaturity of myosin isoform expression observed 6 days postnatally, indicates that Monodelphis could provide a valuable model for studying early developmental events in the jaw-closer muscles and their spindles.

  8. Lessons from mammalian hibernators: molecular insights into striated muscle plasticity and remodeling.

    PubMed

    Tessier, Shannon N; Storey, Kenneth B

    2016-05-01

    Striated muscle shows an amazing ability to adapt its structural apparatus based on contractile activity, loading conditions, fuel supply, or environmental factors. Studies with mammalian hibernators have identified a variety of molecular pathways which are strategically regulated and allow animals to endure multiple stresses associated with the hibernating season. Of particular interest is the observation that hibernators show little skeletal muscle atrophy despite the profound metabolic rate depression and mechanical unloading that they experience during long weeks of torpor. Additionally, the cardiac muscle of hibernators must adjust to low temperature and reduced perfusion, while the strength of contraction increases in order to pump cold, viscous blood. Consequently, hibernators hold a wealth of knowledge as it pertains to understanding the natural capacity of myocytes to alter structural, contractile and metabolic properties in response to environmental stimuli. The present review outlines the molecular and biochemical mechanisms which play a role in muscular atrophy, hypertrophy, and remodeling. In this capacity, four main networks are highlighted: (1) antioxidant defenses, (2) the regulation of structural, contractile and metabolic proteins, (3) ubiquitin proteosomal machinery, and (4) macroautophagy pathways. Subsequently, we discuss the role of transcription factors nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Myocyte enhancer factor 2 (MEF2), and Forkhead box (FOXO) and their associated posttranslational modifications as it pertains to regulating each of these networks. Finally, we propose that comparing and contrasting these concepts to data collected from model organisms able to withstand dramatic changes in muscular function without injury will allow researchers to delineate physiological versus pathological responses.

  9. Muscle niche-driven Insulin-Notch-Myc cascade reactivates dormant Adult Muscle Precursors in Drosophila.

    PubMed

    Aradhya, Rajaguru; Zmojdzian, Monika; Da Ponte, Jean Philippe; Jagla, Krzysztof

    2015-12-09

    How stem cells specified during development keep their non-differentiated quiescent state, and how they are reactivated, remain poorly understood. Here, we applied a Drosophila model to follow in vivo behavior of adult muscle precursors (AMPs), the transient fruit fly muscle stem cells. We report that emerging AMPs send out thin filopodia that make contact with neighboring muscles. AMPs keep their filopodia-based association with muscles throughout their dormant state but also when they start to proliferate, suggesting that muscles could play a role in AMP reactivation. Indeed, our genetic analyses indicate that muscles send inductive dIlp6 signals that switch the Insulin pathway ON in closely associated AMPs. This leads to the activation of Notch, which regulates AMP proliferation via dMyc. Altogether, we report that Drosophila AMPs display homing behavior to muscle niche and that the niche-driven Insulin-Notch-dMyc cascade plays a key role in setting the activated state of AMPs.

  10. Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain

    PubMed Central

    Sun, Gerald J.; Zhou, Yi; Stadel, Ryan P.; Moss, Jonathan; Yong, Jing Hui A.; Ito, Shiori; Kawasaki, Nicholas K.; Phan, Alexander T.; Oh, Justin H.; Modak, Nikhil; Reed, Randall R.; Toni, Nicolas; Song, Hongjun; Ming, Guo-li

    2015-01-01

    In a classic model of mammalian brain formation, precursors of principal glutamatergic neurons migrate radially along radial glia fibers whereas GABAergic interneuron precursors migrate tangentially. These migration modes have significant implications for brain function. Here we used clonal lineage tracing of active radial glia-like neural stem cells in the adult mouse dentate gyrus and made the surprising discovery that proliferating neuronal precursors of glutamatergic granule neurons exhibit significant tangential migration along blood vessels, followed by limited radial migration. Genetic birthdating and morphological and molecular analyses pinpointed the neuroblast stage as the main developmental window when tangential migration occurs. We also developed a partial “whole-mount” dentate gyrus preparation and observed a dense plexus of capillaries, with which only neuroblasts, among the entire population of progenitors, are directly associated. Together, these results provide insight into neuronal migration in the adult mammalian nervous system. PMID:26170290

  11. Differential effects of chronic overload-induced muscle hypertrophy on mTOR and MAPK signaling pathways in adult and aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined activation of the mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) signaling pathways in adult (Y; 6 mo old; n = 16) and aged (O; 30 mo old; n = 16) male rats (Fischer 344 x Brown Norway) subjected to chronic overload-induced muscle hypertrophy of the plan...

  12. Sumoylated α-skeletal muscle actin in the skeletal muscle of adult rats.

    PubMed

    Uda, Munehiro; Kawasaki, Hiroaki; Iizumi, Kyoichi; Shigenaga, Ayako; Baba, Takeshi; Naito, Hisashi; Yoshioka, Toshitada; Yamakura, Fumiyuki

    2015-11-01

    Skeletal muscles are composed of two major muscle fiber types: slow-twitch oxidative fibers and fast-twitch glycolytic fibers. The proteins in these muscle fibers are known to differ in their expression, relative abundance, and post-translational modifications. In this study, we report a previously unreported post-translational modification of α-skeletal muscle actin in the skeletal muscles of adult male F344 rats in vivo. Using two-dimensional electrophoresis (2D-PAGE), we first examined the differences in the protein expression profiles between the soleus and plantaris muscles. We found higher intensity protein spots at approximately 60 kDa and pH 9 on 2D-PAGE for the soleus muscle compared with the plantaris muscle. These spots were identified as α-skeletal muscle actin by liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry and western blot analyses. In addition, we found that the 60 kDa α-skeletal muscle actin is modified by small ubiquitin-like modifier (SUMO) 1, using 2D-PAGE and western blot analyses. Furthermore, we found that α-skeletal muscle actin with larger molecular weight was localized in the nuclear and cytosol of the skeletal muscle, but not in the myofibrillar fraction by the combination of subcellular fractionation and western blot analyses. These results suggest that α-skeletal muscle actin is modified by SUMO-1 in the skeletal muscles, localized in nuclear and cytosolic fractions, and the extent of this modification is much higher in the slow muscles than in the fast muscles. This is the first study to show the presence of SUMOylated actin in animal tissues.

  13. Muscle MRI Findings in Childhood/Adult Onset Pompe Disease Correlate with Muscle Function

    PubMed Central

    Figueroa-Bonaparte, Sebastián; Segovia, Sonia; Llauger, Jaume; Belmonte, Izaskun; Pedrosa, Irene; Alejaldre, Aída; Mayos, Mercè; Suárez-Cuartín, Guillermo; Gallardo, Eduard; Illa, Isabel; Díaz-Manera, Jordi

    2016-01-01

    Objectives Enzyme replacement therapy has shown to be effective for childhood/adult onset Pompe disease (AOPD). The discovery of biomarkers useful for monitoring disease progression is one of the priority research topics in Pompe disease. Muscle MRI could be one possible test but the correlation between muscle MRI and muscle strength and function has been only partially addressed so far. Methods We studied 34 AOPD patients using functional scales (Manual Research Council scale, hand held myometry, 6 minutes walking test, timed to up and go test, time to climb up and down 4 steps, time to walk 10 meters and Motor Function Measure 20 Scale), respiratory tests (Forced Vital Capacity seated and lying, Maximun Inspiratory Pressure and Maximum Expiratory Pressure), daily live activities scales (Activlim) and quality of life scales (Short Form-36 and Individualized Neuromuscular Quality of Life questionnaire). We performed a whole body muscle MRI using T1w and 3-point Dixon imaging centered on thighs and lower trunk region. Results T1w whole body muscle MRI showed a homogeneous pattern of muscle involvement that could also be found in pre-symptomatic individuals. We found a strong correlation between muscle strength, muscle functional scales and the degree of muscle fatty replacement in muscle MRI analyzed using T1w and 3-point Dixon imaging studies. Moreover, muscle MRI detected mild degree of fatty replacement in paraspinal muscles in pre-symptomatic patients. Conclusion Based on our findings, we consider that muscle MRI correlates with muscle function in patients with AOPD and could be useful for diagnosis and follow-up in pre-symptomatic and symptomatic patients under treatment. Take home message Muscle MRI correlates with muscle function in patients with AOPD and could be useful to follow-up patients in daily clinic. PMID:27711114

  14. Satellite cell proliferation in adult skeletal muscle

    NASA Technical Reports Server (NTRS)

    Booth, Frank W. (Inventor); Thomason, Donald B. (Inventor); Morrison, Paul R. (Inventor); Stancel, George M. (Inventor)

    1995-01-01

    Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stable expression of eukaryotic or prokaryotic foreign genes in tissues of living animals is described. More specifically, methods of incorporating foreign genes into mitotically active cells are disclosed. The constitutive and stable expression of E. coli .beta.-galactosidase gene under the promoter control of the Moloney murine leukemia virus long terminal repeat is employed as a particularly preferred embodiment, by way of example, establishes the model upon which the incorporation of a foreign gene into a mitotically-active living eukaryotic tissue is based. Use of the described methods in therapeutic treatments for genetic diseases, such as those muscular degenerative diseases, is also presented. In muscle tissue, the described processes result in genetically-altered satellite cells which proliferate daughter myoblasts which preferentially fuse to form a single undamaged muscle fiber replacing damaged muscle tissue in a treated animal. The retroviral vector, by way of example, includes a dystrophin gene construct for use in treating muscular dystrophy. The present invention also comprises an experimental model utilizable in the study of the physiological regulation of skeletal muscle gene expression in intact animals.

  15. Fgf regulates dedifferentiation during skeletal muscle regeneration in adult zebrafish.

    PubMed

    Saera-Vila, Alfonso; Kish, Phillip E; Kahana, Alon

    2016-09-01

    Fibroblast growth factors (Fgfs) regulate critical biological processes such as embryonic development, tissue homeostasis, wound healing, and tissue regeneration. In zebrafish, Fgf signaling plays an important role in the regeneration of the spinal cord, liver, heart, fin, and photoreceptors, although its exact mechanism of action is not fully understood. Utilizing an adult zebrafish extraocular muscle (EOM) regeneration model, we demonstrate that blocking Fgf receptor function using either a chemical inhibitor (SU5402) or a dominant-negative transgenic construct (dnFGFR1a:EGFP) impairs muscle regeneration. Adult zebrafish EOMs regenerate through a myocyte dedifferentiation process, which involves a muscle-to-mesenchyme transition and cell cycle reentry by differentiated myocytes. Blocking Fgf signaling reduced cell proliferation and active caspase 3 levels in the regenerating muscle with no detectable levels of apoptosis, supporting the hypothesis that Fgf signaling is involved in the early steps of dedifferentiation. Fgf signaling in regenerating myocytes involves the MAPK/ERK pathway: inhibition of MEK activity with U0126 mimicked the phenotype of the Fgf receptor inhibition on both muscle regeneration and cell proliferation, and activated ERK (p-ERK) was detected in injured muscles by immunofluorescence and western blot. Interestingly, following injury, ERK2 expression is specifically induced and activated by phosphorylation, suggesting a key role in muscle regeneration. We conclude that the critical early steps of myocyte dedifferentiation in EOM regeneration are dependent on Fgf signaling.

  16. Ca2+ release from the sarcoplasmic reticulum compared in amphibian and mammalian skeletal muscle

    PubMed Central

    1996-01-01

    their direct control, the greater ratio in frogs may correspond to the relative excess of Ca2+ release channels over voltage sensors apparent in binding measurements. From the marked differences in voltage dependence of the ratio, as well as consideration of Ca(2+)-induced release models, we derive indications of fundamental differences in control mechanisms between mammalian and amphibian muscle. PMID:8741727

  17. Activation of mammalian target of rapamycin signaling in skeletal muscle of neonatal chicks: effects of dietary leucine and age.

    PubMed

    Deng, Huiling; Zheng, Aijuan; Liu, Guohua; Chang, Wenhuan; Zhang, Shu; Cai, Huiyi

    2014-01-01

    The mammalian target of rapamycin (mTOR) signaling pathway is necessary for cellular protein synthesis regulation. Leucine was reported to stimulate muscle protein synthesis in mammalian embryos and neonates, but in higher animals (chickens) the effect of dietary leucine on mTOR signaling is unknown. Thus, we investigated the effects of dietary leucine and age on mRNA expression and phosphorylation of mTOR as well as its downstream targets, ribosomal protein S6 kinase (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1) in chick pectoral muscles. One hundred eighty newly hatched male chicks were randomly assigned to 1 of 3 dietary leucine treatment groups (1.43, 1.73, and 2.03% leucine) for 14 d, respectively. Each treatment group consisted of 6 cages with 10 chicks each. On d 3, 7, and 14, plasma insulin and leucine were measured and target gene expression and phosphorylation was assessed. Dietary leucine influenced plasma leucine but not insulin, and plasma leucine and insulin declined with chick age. The mTOR, S6K1, and 4E-BP1 mRNA expression and phosphorylation within chick pectoral muscles were upregulated with increased dietary leucine but downregulated with increased chick age. Thus, high dietary leucine activates target of rapamycin signaling pathways in skeletal muscle of neonatal chicks to stimulate muscle protein synthesis, and this pathway is attenuated with aging.

  18. The head and neck muscles of the serval and tiger: homologies, evolution, and proposal of a mammalian and a veterinary muscle ontology.

    PubMed

    Diogo, Rui; Pastor, Francisco; De Paz, Felix; Potau, Josep M; Bello-Hellegouarch, Gaëlle; Ferrero, Eva M; Fisher, Rebecca E

    2012-12-01

    Here we describe the head and neck muscles of members of the two extant felid subfamilies (Leptailurus serval: Felinae; Panthera tigris: Pantherinae) and compare these muscles with those of other felids, other carnivorans (e.g., domestic dogs), other eutherian mammals (e.g., rats, tree-shrews and modern humans), and noneutherian mammals including monotremes. Another major goal of the article is to discuss and help clarify nomenclatural discrepancies found in the Nomina Anatomica Veterinaria and in veterinary atlases and textbooks that use cats and dogs as models to understand the anatomy of domestic mammals and to stress differences with modern humans. We propose a unifying nomenclature that is expanded to all the head and neck muscles and to all mammalian taxa in order to help build veterinary and mammalian muscle ontologies. Our observations and comparisons and the specific use of this nomenclature point out that felids such as tigers and servals and other carnivorans such as dogs have more facial muscle structures related to the mobility of both the auricular and orbital regions than numerous other mammals, including modern humans, which might be the result of an ancient adaptation related to the remarkable predatory capacities of carnivorans. Interestingly, the skeletal differences, mainly concerning the hyoid apparatus, pharynx, and larynx, that are likely associated with the different types of vocalizations seen in the Felinae (mainly purring) and Pantherinae (mainly roaring) are not accompanied by clear differences in the musculature connected to these structures in the feline L. serval and the pantherine P. tigris.

  19. Temporal features of adult neurogenesis: differences and similarities across mammalian species

    PubMed Central

    Brus, Maïna; Keller, Matthieu; Lévy, Frédéric

    2013-01-01

    Production of new neurons continues throughout life in most invertebrates and vertebrates like crustaceans, fishes, reptiles, birds, and mammals including humans. Most studies have been carried out on rodent models and demonstrated that adult neurogenesis is located mainly in two structures, the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ). If adult neurogenesis is well preserved throughout evolution, yet there are however some features which differ between species. The present review proposes to target similarities and differences in the mechanism of mammalian adult neurogenesis by comparing selected species including humans. We will highlight the cellular composition and morphological organization of the SVZ in primates which differs from that of rodents and may be of functional relevance. We will particularly focus on the dynamic of neuronal maturation in rodents, primates, and humans but also in sheep which appears to be an interesting model due to its similarities with the primate brain. PMID:23935563

  20. Biology of the Sertoli Cell in the Fetal, Pubertal, and Adult Mammalian Testis.

    PubMed

    Chojnacka, Katarzyna; Zarzycka, Marta; Mruk, Dolores D

    A healthy man typically produces between 50 × 10(6) and 200 × 10(6) spermatozoa per day by spermatogenesis; in the absence of Sertoli cells in the male gonad, this individual would be infertile. In the adult testis, Sertoli cells are sustentacular cells that support germ cell development by secreting proteins and other important biomolecules that are essential for germ cell survival and maturation, establishing the blood-testis barrier, and facilitating spermatozoa detachment at spermiation. In the fetal testis, on the other hand, pre-Sertoli cells form the testis cords, the future seminiferous tubules. However, the role of pre-Sertoli cells in this process is much less clear than the function of Sertoli cells in the adult testis. Within this framework, we provide an overview of the biology of the fetal, pubertal, and adult Sertoli cell, highlighting relevant cell biology studies that have expanded our understanding of mammalian spermatogenesis.

  1. Potential for neural regeneration after neurotoxic injury in the adult mammalian retina

    PubMed Central

    Ooto, Sotaro; Akagi, Tadamichi; Kageyama, Ryoichiro; Akita, Joe; Mandai, Michiko; Honda, Yoshihito; Takahashi, Masayo

    2004-01-01

    It has long been believed that the retina of mature mammals is incapable of regeneration. In this study, using the N-methyl-d-aspartate neurotoxicity model of adult rat retina, we observed that some Müller glial cells were stimulated to proliferate in response to a toxic injury and produce bipolar cells and rod photoreceptors. Although these newly produced neurons were limited in number, retinoic acid treatment promoted the number of regenerated bipolar cells. Moreover, misexpression of basic helix–loop–helix and homeobox genes promoted the induction of amacrine, horizontal, and rod photoreceptor specific phenotypes. These findings demonstrated that retinal neurons regenerated even in adult mammalian retina after toxic injury. Furthermore, we could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes. The Müller glial cells constitute a potential source for the regeneration of adult mammalian retina and can be a target for drug delivery and gene therapy in retinal degenerative diseases. PMID:15353594

  2. Control of adult neurogenesis by programmed cell death in the mammalian brain.

    PubMed

    Ryu, Jae Ryun; Hong, Caroline Jeeyeon; Kim, Joo Yeon; Kim, Eun-Kyoung; Sun, Woong; Yu, Seong-Woon

    2016-04-21

    The presence of neural stem cells (NSCs) and the production of new neurons in the adult brain have received great attention from scientists and the public because of implications to brain plasticity and their potential use for treating currently incurable brain diseases. Adult neurogenesis is controlled at multiple levels, including proliferation, differentiation, migration, and programmed cell death (PCD). Among these, PCD is the last and most prominent process for regulating the final number of mature neurons integrated into neural circuits. PCD can be classified into apoptosis, necrosis, and autophagic cell death and emerging evidence suggests that all three may be important modes of cell death in neural stem/progenitor cells. However, the molecular mechanisms that regulate PCD and thereby impact the intricate balance between self-renewal, proliferation, and differentiation during adult neurogenesis are not well understood. In this comprehensive review, we focus on the extent, mechanism, and biological significance of PCD for the control of adult neurogenesis in the mammalian brain. The role of intrinsic and extrinsic factors in the regulation of PCD at the molecular and systems levels is also discussed. Adult neurogenesis is a dynamic process, and the signals for differentiation, proliferation, and death of neural progenitor/stem cells are closely interrelated. A better understanding of how adult neurogenesis is influenced by PCD will help lead to important insights relevant to brain health and diseases.

  3. Child—Adult Differences in Muscle Activation — A Review

    PubMed Central

    Dotan, Raffy; Mitchell, Cameron; Cohen, Rotem; Klentrou, Panagiota; Gabriel, David; Falk, Bareket

    2013-01-01

    Children differ from adults in many muscular performance attributes such as size-normalized strength and power, endurance, fatigability and the recovery from exhaustive exercise, to name just a few. Metabolic attributes, such as glycolytic capacity, substrate utilization, and VO2 kinetics also differ markedly between children and adults. Various factors, such as dimensionality, intramuscular synchronization, agonist-antagonist coactivation, level of volitional activation, or muscle composition, can explain some, but not all of the observed differences. It is hypothesized that, compared with adults, children are substantially less capable of recruiting or fully employing their higher-threshold, type-II motor units. The review presents and evaluates the wealth of information and possible alternative factors in explaining the observations. Although conclusive evidence is still lacking, only this hypothesis of differential motor-unit activation in children and adults, appears capable of accounting for all observed child—adult differences, whether on its own or in conjunction with other factors. PMID:22433260

  4. Identification of mammalian noggin and its expression in the adult nervous system.

    PubMed

    Valenzuela, D M; Economides, A N; Rojas, E; Lamb, T M; Nuñez, L; Jones, P; Lp, N Y; Espinosa, R; Brannan, C I; Gilbert, D J

    1995-09-01

    The multiple roles of noggin during dorsal fate specification in Xenopus embryos, together with noggin's ability to directly induce neural tissue, inspired an effort to determine whether a similar molecule exists in mammals. Here we describe the identification of human and rat noggin and explore their expression patterns; we also localize the human NOGGIN gene to chromosome 17q22, and the mouse gene to a syntenic region of chromosome 11. Mammalian noggin is remarkably similar in its sequence to Xenopus noggin, and is similarly active in induction assays performed on Xenopus embryo tissues. In the adult mammal, noggin is most notably expressed in particular regions of the nervous system, such as the tufted cells of the olfactory bulb, the piriform cortex of the brain, and the Purkinje cells of the cerebellum, suggesting that one of the earliest acting neural inducers also has important roles in the adult nervous system.

  5. Muscle power failure in mobility-limited adults: preserved single muscle fibre function despite reduced whole muscle size, quality and neuromuscular activiation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study investigated the physiological and gender determinants of the age-related loss of muscle power in 31 healthy middle-aged adults (aged 40-55 years), 28 healthy older adults (70-85 years) and 34 mobility-limited older adults (70-85 years). We hypothesized that leg extensor muscle power woul...

  6. Adult motor axons preferentially reinnervate predegenerated muscle nerve.

    PubMed

    Abdullah, M; O'Daly, A; Vyas, A; Rohde, C; Brushart, T M

    2013-11-01

    Preferential motor reinnervation (PMR) is the tendency for motor axons regenerating after repair of mixed nerve to reinnervate muscle nerve and/or muscle rather than cutaneous nerve or skin. PMR may occur in response to the peripheral nerve pathway alone in juvenile rats (Brushart, 1993; Redett et al., 2005), yet the ability to identify and respond to specific pathway markers is reportedly lost in adults (Uschold et al., 2007). The experiments reported here evaluate the relative roles of pathway and end organ in the genesis of PMR in adult rats. Fresh and 2-week predegenerated femoral nerve grafts were transferred in correct or reversed alignment to replace the femoral nerves of previously unoperated Lewis rats. After 8 weeks of regeneration the motoneurons projecting through the grafts to recipient femoral cutaneous and muscle branches and their adjacent end organs were identified by retrograde labeling. Motoneuron counts were subjected to Poisson regression analysis to determine the relative roles of pathway and end organ identity in generating PMR. Transfer of fresh grafts did not result in PMR, whereas substantial PMR was observed when predegenerated grafts were used. Similarly, the pathway through which motoneurons reached the muscle had a significant impact on PMR when grafts were predegenerated, but not when they were fresh. Comparison of the relative roles of pathway and end organ in generating PMR revealed that neither could be shown to be more important than the other. These experiments demonstrate unequivocally that adult muscle nerve and cutaneous nerve differ in qualities that can be detected by regenerating adult motoneurons and that can modify their subsequent behavior. They also reveal that two weeks of Wallerian degeneration modify the environment in the graft from one that provides no modality-specific cues for motor neurons to one that actively promotes PMR.

  7. Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family

    PubMed Central

    Porrello, Enzo R.; Mahmoud, Ahmed I.; Simpson, Emma; Johnson, Brett A.; Grinsfelder, David; Canseco, Diana; Mammen, Pradeep P.; Rothermel, Beverly A.; Olson, Eric N.; Sadek, Hesham A.

    2013-01-01

    We recently identified a brief time period during postnatal development when the mammalian heart retains significant regenerative potential after amputation of the ventricular apex. However, one major unresolved question is whether the neonatal mouse heart can also regenerate in response to myocardial ischemia, the most common antecedent of heart failure in humans. Here, we induced ischemic myocardial infarction (MI) in 1-d-old mice and found that this results in extensive myocardial necrosis and systolic dysfunction. Remarkably, the neonatal heart mounted a robust regenerative response, through proliferation of preexisting cardiomyocytes, resulting in full functional recovery within 21 d. Moreover, we show that the miR-15 family of microRNAs modulates neonatal heart regeneration through inhibition of postnatal cardiomyocyte proliferation. Finally, we demonstrate that inhibition of the miR-15 family from an early postnatal age until adulthood increases myocyte proliferation in the adult heart and improves left ventricular systolic function after adult MI. We conclude that the neonatal mammalian heart can regenerate after myocardial infarction through proliferation of preexisting cardiomyocytes and that the miR-15 family contributes to postnatal loss of cardiac regenerative capacity. PMID:23248315

  8. Volume regulation in mammalian skeletal muscle: the role of sodium–potassium–chloride cotransporters during exposure to hypertonic solutions

    PubMed Central

    Lindinger, Michael I; Leung, Matthew; Trajcevski, Karin E; Hawke, Thomas J

    2011-01-01

    Abstract Controversy exists as to whether mammalian skeletal muscle is capable of volume regulation in response to changes in extracellular osmolarity despite evidence that muscle fibres have the required ion transport mechanisms to transport solute and water in situ. We addressed this issue by studying the ability of skeletal muscle to regulate volume during periods of induced hyperosmotic stress using single, mouse extensor digitorum longus (EDL) muscle fibres and intact muscle (soleus and EDL). Fibres and intact muscles were loaded with the fluorophore, calcein, and the change in muscle fluorescence and width (single fibres only) used as a metric of volume change. We hypothesized that skeletal muscle exposed to increased extracellular osmolarity would elicit initial cellular shrinkage followed by a regulatory volume increase (RVI) with the RVI dependent on the sodium–potassium–chloride cotransporter (NKCC). We found that single fibres exposed to a 35% increase in extracellular osmolarity demonstrated a rapid, initial 27–32% decrease in cell volume followed by a RVI which took 10–20 min and returned cell volume to 90–110% of pre-stimulus values. Within intact muscle, exposure to increased extracellular osmolarity of varying degrees also induced a rapid, initial shrinkage followed by a gradual RVI, with a greater rate of initial cell shrinkage and a longer time for RVI to occur with increasing extracellular tonicities. Furthermore, RVI was significantly faster in slow-twitch soleus than fast-twitch EDL. Pre-treatment of muscle with bumetanide (NKCC inhibitor) or ouabain (Na+,K+-ATPase inhibitor), increased the initial volume loss and impaired the RVI response to increased extracellular osmolarity indicating that the NKCC is a primary contributor to volume regulation in skeletal muscle. It is concluded that mouse skeletal muscle initially loses volume then exhibits a RVI when exposed to increases in extracellular osmolarity. The rate of RVI is dependent

  9. Volume regulation in mammalian skeletal muscle: the role of sodium-potassium-chloride cotransporters during exposure to hypertonic solutions.

    PubMed

    Lindinger, Michael I; Leung, Matthew; Trajcevski, Karin E; Hawke, Thomas J

    2011-06-01

    Controversy exists as to whether mammalian skeletal muscle is capable of volume regulation in response to changes in extracellular osmolarity despite evidence that muscle fibres have the required ion transport mechanisms to transport solute and water in situ. We addressed this issue by studying the ability of skeletal muscle to regulate volume during periods of induced hyperosmotic stress using single, mouse extensor digitorum longus (EDL) muscle fibres and intact muscle (soleus and EDL). Fibres and intact muscles were loaded with the fluorophore, calcein, and the change in muscle fluorescence and width (single fibres only) used as a metric of volume change. We hypothesized that skeletal muscle exposed to increased extracellular osmolarity would elicit initial cellular shrinkage followed by a regulatory volume increase (RVI) with the RVI dependent on the sodium–potassium–chloride cotransporter (NKCC). We found that single fibres exposed to a 35% increase in extracellular osmolarity demonstrated a rapid, initial 27–32% decrease in cell volume followed by a RVI which took 10-20 min and returned cell volume to 90–110% of pre-stimulus values. Within intact muscle, exposure to increased extracellular osmolarity of varying degrees also induced a rapid, initial shrinkage followed by a gradual RVI, with a greater rate of initial cell shrinkage and a longer time for RVI to occur with increasing extracellular tonicities. Furthermore, RVI was significantly faster in slow-twitch soleus than fast-twitch EDL. Pre-treatment of muscle with bumetanide (NKCC inhibitor) or ouabain (Na+,K+-ATPase inhibitor), increased the initial volume loss and impaired the RVI response to increased extracellular osmolarity indicating that the NKCC is a primary contributor to volume regulation in skeletal muscle. It is concluded that mouse skeletal muscle initially loses volume then exhibits a RVI when exposed to increases in extracellular osmolarity. The rate of RVI is dependent on the

  10. Continued Expression of Neonatal Myosin Heavy Chain in Adult Dystrophic Skeletal Muscle

    NASA Astrophysics Data System (ADS)

    Bandman, Everett

    1985-02-01

    The expression of myosin heavy chain isoforms was examined in normal and dystrophic chicken muscle with a monoclonal antibody specific for neonatal myosin. Adult dystrophic muscle continued to contain neonatal myosin long after it disappeared from adult normal muscle. A new technique involving western blotting and peptide mapping demonstrated that the immunoreactive myosin in adult dystrophic muscle was identical to that found in neonatal normal muscle. Immunocytochemistry revealed that all fibers in the dystrophic muscle failed to repress neonatal myosin heavy chain. These studies suggest that muscular dystrophy inhibits the myosin gene switching that normally occurs during muscle maturation.

  11. Comparative analysis of mesenchymal stem cells from adult mouse adipose, muscle, and fetal muscle.

    PubMed

    Lei, Hulong; Yu, Bing; Huang, Zhiqing; Yang, Xuerong; Liu, Zehui; Mao, Xiangbing; Tian, Gang; He, Jun; Han, Guoquan; Chen, Hong; Mao, Qian; Chen, Daiwen

    2013-02-01

    Recently, increasing evidence supports that adult stem cells are the part of a natural system for tissue growth and repair. This study focused on the differences of mesenchymal stem cells from adult adipose (ADSCs), skeletal muscle (MDSCs) and fetal muscle (FMSCs) in biological characteristics, which is the key to cell therapy success. Stem cell antigen 1 (Sca-1) expression of MDSCs and FMSCs at passage 3 was two times more than that at passage 1 (P < 0.0001). After 28-day myogenic induction, higher expression levels of skeletal muscle-specific genes were observed in MDSCs than FMSCs (P < 0.01), and the lowest expression levels were demonstrated in ADSCs among three cells (P < 0.01). Besides, M-Cad and MyHC expressions in ADSCs were not detected by immunofluorescence or real-time quantitative PCR. Furthermore, after 14 days adipogenic induction, PPARγ2, LPL and aP2 mRNA expressions were higher in ADSCs vs. MDSCs (P < 0.01). Besides, MSCs from adult or fetal muscle expressed higher OCN and OPN than ADSCs after 28 days osteogenic induction (P < 0.01). Taken together, our results suggested that cell source and developmental stage had great impacts on biological properties of mesenchymal stem cells, and proper consideration of all the issues is necessary.

  12. A comparative analysis of the encapsulated end-organs of mammalian skeletal muscles and of their sensory nerve endings.

    PubMed

    Banks, R W; Hulliger, M; Saed, H H; Stacey, M J

    2009-06-01

    The encapsulated sensory endings of mammalian skeletal muscles are all mechanoreceptors. At the most basic functional level they serve as length sensors (muscle spindle primary and secondary endings), tension sensors (tendon organs), and pressure or vibration sensors (lamellated corpuscles). At a higher functional level, the differing roles of individual muscles in, for example, postural adjustment and locomotion might be expected to be reflected in characteristic complements of the various end-organs, their sensory endings and afferent nerve fibres. This has previously been demonstrated with regard to the number of muscle-spindle capsules; however, information on the other types of end-organ, as well as the complements of primary and secondary endings of the spindles themselves, is sporadic and inconclusive regarding their comparative provision in different muscles. Our general conclusion that muscle-specific variability in the provision of encapsulated sensory endings does exist demonstrates the necessity for the acquisition of more data of this type if we are to understand the underlying adaptive relationships between motor control and the structure and function of skeletal muscle. The present quantitative and comparative analysis of encapsulated muscle afferents is based on teased, silver-impregnated preparations. We begin with a statistical analysis of the number and distribution of muscle-spindle afferents in hind-limb muscles of the cat, particularly tenuissimus. We show that: (i) taking account of the necessity for at least one primary ending to be present, muscles differ significantly in the mean number of additional afferents per spindle capsule; (ii) the frequency of occurrence of spindles with different sensory complements is consistent with a stochastic, rather than deterministic, developmental process; and (iii) notwithstanding the previous finding, there is a differential distribution of spindles intramuscularly such that the more complex ones tend

  13. Voltage-dependent Dynamic FRET Signals from the Transverse Tubules in Mammalian Skeletal Muscle Fibers

    PubMed Central

    DiFranco, Marino; Capote, Joana; Quiñonez, Marbella; Vergara, Julio L.

    2007-01-01

    Two hybrid voltage-sensing systems based on fluorescence resonance energy transfer (FRET) were used to record membrane potential changes in the transverse tubular system (TTS) and surface membranes of adult mice skeletal muscle fibers. Farnesylated EGFP or ECFP (EGFP-F and ECFP-F) were used as immobile FRET donors, and either non-fluorescent (dipicrylamine [DPA]) or fluorescent (oxonol dye DiBAC4(5)) lipophilic anions were used as mobile energy acceptors. Flexor digitorum brevis (FDB) muscles were transfected by in vivo electroporation with pEGFP-F and pECFP-F. Farnesylated fluorescent proteins were efficiently expressed in the TTS and surface membranes. Voltage-dependent optical signals resulting from resonance energy transfer from fluorescent proteins to DPA were named QRET transients, to distinguish them from FRET transients recorded using DiBAC4(5). The peak ΔF/F of QRET transients elicited by action potential stimulation is twice larger in fibers expressing ECFP-F as those with EGFP-F (7.1% vs. 3.6%). These data provide a unique experimental demonstration of the importance of the spectral overlap in FRET. The voltage sensitivity of QRET and FRET signals was demonstrated to correspond to the voltage-dependent translocation of the charged acceptors, which manifest as nonlinear components in current records. For DPA, both electrical and QRET data were predicted by radial cable model simulations in which the maximal time constant of charge translocation was 0.6 ms. FRET signals recorded in response to action potentials in fibers stained with DiBAC4(5) exhibit ΔF/F amplitudes as large as 28%, but their rising phase was slower than those of QRET signals. Model simulations require a time constant for charge translocation of 1.6 ms in order to predict current and FRET data. Our results provide the basis for the potential use of lipophilic ions as tools to test for fast voltage-dependent conformational changes of membrane proteins in the TTS. PMID:18040060

  14. The neonate versus adult mammalian immune system in cardiac repair and regeneration.

    PubMed

    Sattler, Susanne; Rosenthal, Nadia

    2016-07-01

    The immune system is a crucial player in tissue homeostasis and wound healing. A sophisticated cascade of events triggered upon injury ensures protection from infection and initiates and orchestrates healing. While the neonatal mammal can readily regenerate damaged tissues, adult regenerative capacity is limited to specific tissue types, and in organs such as the heart, adult wound healing results in fibrotic repair and loss of function. Growing evidence suggests that the immune system greatly influences the balance between regeneration and fibrotic repair. The neonate mammalian immune system has impaired pro-inflammatory function, is prone to T-helper type 2 responses and has an immature adaptive immune system skewed towards regulatory T cells. While these characteristics make infants susceptible to infection and prone to allergies, it may also provide an immunological environment permissive of regeneration. In this review we will give a comprehensive overview of the immune cells involved in healing and regeneration of the heart and explore differences between the adult and neonate immune system that may explain differences in regenerative ability. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  15. Current recordings at the single channel level in adult mammalian isolated cardiomyocytes.

    PubMed

    Guinamard, Romain; Hof, Thomas; Sallé, Laurent

    2014-01-01

    This chapter describes appropriate methods to investigate mammalian cardiac channels properties at the single channel level. Cell isolation is performed from new born or adult heart by enzymatic digestion on minced tissue or using the Langendorff apparatus. Isolation proceeding is suitable for rabbit, rat, and mouse hearts. In addition, isolation of human atrial cardiomyocytes is described. Such freshly isolated cells or cells maintained in primary culture are suitable for patch-clamp studies. Here we describe the single channel variants of the patch-clamp technique (cell-attached, inside-out, outside-out) used to investigate channel properties. Proceedings for the evaluation of biophysical properties such as conductance, ionic selectivity, regulations by extracellular and intracellular mechanisms are described. To illustrate the study, we provide an example by the characterization of a calcium-activated non-selective cation channel (TRPM4).

  16. [Proliferation of adult mammalian ventricular cardiomyocytes: a sporadic but feasible phenomenon].

    PubMed

    Vargas-González, Alvaro

    2014-01-01

    Proliferation of adult mammalian ventricular cardiomyocytes has been ruled out by some researchers, who have argued that these cells are terminally differentiated; however, this dogma has been rejected because other researchers have reported that these cells can present the processes necessary to proliferate, that is, DNA synthesis, mitosis and cytokinesis when the heart is damaged experimentally through pharmacological and surgical strategies or due to pathological conditions concerning the cardiovascular system. This review integrates some of the available works in the literature evaluating the DNA synthesis, mitosis and cytokinesis in these myocytes, when the myocardium is damaged, with the purpose of knowing if their proliferation can be considered as a feasible phenomenon. The review is concluded with a reflection about the perspectives of the knowledge generated in this area.

  17. Presynaptic inhibition of muscle spindle and tendon organ afferents in the mammalian spinal cord.

    PubMed

    Rudomin, P

    1990-12-01

    More than 30 years ago, Frank and Fuortes proposed that the synaptic effectiveness of muscle spindle afferents associated with spinal motoneurones could be diminished by the activation of nerves from flexor muscles. Since that time, research has focused on disclosing the mode of operation and the spinal pathways involved in this presynaptic inhibitory control. Initially, it was assumed that the same last-order interneurones mediated presynaptic inhibition of both muscle spindle and tendon organ afferent fibres. More recent evidence indicates that the synaptic effectiveness of these two groups of afferents is controlled by separate sets of GABAergic interneurones synapsing directly with the intraspinal terminals of the afferent fibres. This unique arrangement allows for selective control of the information on muscle length or muscle tension, despite the convergence of muscle spindle and tendon organ afferents on second-order interneurones.

  18. Electrically induced muscle cramps induce hypertrophy of calf muscles in healthy adults

    PubMed Central

    Behringer, M.; Moser, M.; Montag, J.; McCourt, M.; Tenner, D.; Mester, J.

    2015-01-01

    Objectives: Skeletal muscles usually cramp at short lengths, where the tension that can be exerted by muscle fibers is low. Since high tension is an important anabolic stimulus, it is questionable if cramps can induce hypertrophy and strength gains. In the present study we investigated if electrically induced cramps (EIMCs) can elicit these adaptations. Methods: 15 healthy male adults were randomly assigned to an intervention (IG; n=10) and a control group (CG; n=5). The cramp protocol (CP) applied twice a week to one leg of the IG, consisted of 3x6 EIMCs, of 5 s each. Calf muscles of the opposite leg were stimulated equally, but were hindered from cramping by fixating the ankle at 0° plantar flexion (nCP). Results: After six weeks, the cross sectional area of the triceps surae was similarly increased in both the CP (+9.0±3.4%) and the nCP (+6.8±3.7%). By contrast, force of maximal voluntary contractions, measured at 0° and 30° plantar flexion, increased significantly only in nCP (0°: +8.5±8.8%; 30°: 11.7±13.7%). Conclusion: The present data indicate that muscle cramps can induce hypertrophy in calf muscles, though lacking high tension as an important anabolic stimulus. PMID:26032216

  19. The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes.

    PubMed

    Bergantin, Leandro Bueno; Figueiredo, Leonardo Bruno; Godinho, Rosely Oliveira

    2011-12-01

    The molecular regulation of skeletal muscle proteolysis and the pharmacological screening of anticatabolic drugs have been addressed by measuring tyrosine release from prepubertal rat skeletal muscles, which are thin enough to allow adequate in vitro diffusion of oxygen and substrates. However, the use of muscle at accelerated prepubertal growth has limited the analysis of adult muscle proteolysis or that associated with aging and neurodegenerative diseases. Here we established the adult rat lumbrical muscle (4/hindpaw; 8/rat) as a new in situ experimental model for dynamic measurement of skeletal muscle proteolysis. By incubating lumbrical muscles attached to their individual metatarsal bones in Tyrode solution, we showed that the muscle proteolysis rate of adult and aged rats (3-4 to 24 mo old) is 45-25% of that in prepubertal animals (1 mo old), which makes questionable the usual extrapolation of proteolysis from prepubertal to adult/senile muscles. While acute mechanical injury or 1- to 7-day denervation increased tyrosine release from adult lumbrical muscle by up to 60%, it was reduced by 20-28% after 2-h incubation with β-adrenoceptor agonists, forskolin or phosphodiesterase inhibitor IBMX. Using inhibitors of 26S-proteasome (MG132), lysosome (methylamine), or calpain (E64/leupeptin) systems, we showed that ubiquitin-proteasome is accountable for 40-50% of total lumbrical proteolysis of adult, middle-aged, and aged rats. In conclusion, the lumbrical model allows the analysis of muscle proteolysis rate from prepubertal to senile rats. By permitting eight simultaneous matched measurements per rat, the new model improves similar protocols performed in paired extensor digitorum longus (EDL) muscles from prepubertal rats, optimizing the pharmacological screening of drugs for anticatabolic purposes.

  20. Sensory Response of Transplanted Astrocytes in Adult Mammalian Cortex In Vivo

    PubMed Central

    Zhang, Kuan; Chen, Chunhai; Yang, Zhiqi; He, Wenjing; Liao, Xiang; Ma, Qinlong; Deng, Ping; Lu, Jian; Li, Jingcheng; Wang, Meng; Li, Mingli; Zheng, Lianghong; Zhou, Zhuan; Sun, Wei; Wang, Liting; Jia, Hongbo; Yu, Zhengping; Zhou, Zhou; Chen, Xiaowei

    2016-01-01

    Glial precursor transplantation provides a potential therapy for brain disorders. Before its clinical application, experimental evidence needs to indicate that engrafted glial cells are functionally incorporated into the existing circuits and become essential partners of neurons for executing fundamental brain functions. While previous experiments supporting for their functional integration have been obtained under in vitro conditions using slice preparations, in vivo evidence for such integration is still lacking. Here, we utilized in vivo two-photon Ca2+ imaging along with immunohistochemistry, fluorescent indicator labeling-based axon tracing and correlated light/electron microscopy to analyze the profiles and the functional status of glial precursor cell-derived astrocytes in adult mouse neocortex. We show that after being transplanted into somatosensory cortex, precursor-derived astrocytes are able to survive for more than a year and respond with Ca2+ signals to sensory stimulation. These sensory-evoked responses are mediated by functionally-expressed nicotinic receptors and newly-established synaptic contacts with the host cholinergic afferents. Our results provide in vivo evidence for a functional integration of transplanted astrocytes into adult mammalian neocortex, representing a proof-of-principle for sensory cortex remodeling through addition of essential neural elements. Moreover, we provide strong support for the use of glial precursor transplantation to understand glia-related neural development in vivo. PMID:27405333

  1. An Active Learning Mammalian Skeletal Muscle Lab Demonstrating Contractile and Kinetic Properties of Fast- and Slow-Twitch Muscle

    ERIC Educational Resources Information Center

    Head, S. I.; Arber, M. B.

    2013-01-01

    The fact that humans possess fast and slow-twitch muscle in the ratio of approximately 50% has profound implications for designing exercise training strategies for power and endurance activities. With the growth of exercise and sport science courses, we have seen the need to develop an undergraduate student laboratory that demonstrates the basic…

  2. Preparation of adult muscle fiber-associated stem/precursor cells.

    PubMed

    Conboy, Michael J; Conboy, Irina M

    2010-01-01

    In our studies of muscle regeneration we have developed, modified, and optimized techniques to isolate and study the stem and precursor cells to muscle tissue. Our goals have been to obtain for study muscle fibers in bulk, or the fiber-associated cells, separately from the other cells found in muscle. Using these techniques, myofiber-associated cells may be isolated from neonatal through adult muscle, from resting or from regenerating muscle, thus allowing one to investigate the cellular populations participating during the time course of these events. The protocol is applicable to any age and condition of muscle and may be adapted for other tissues.

  3. Novel Kv3 glycoforms differentially expressed in adult mammalian brain contain sialylated N-glycans.

    PubMed

    Schwalbe, Ruth A; Corey, Melissa J; Cartwright, Tara A

    2008-02-01

    The N-glycan pool of mammalian brain contains remarkably high levels of sialylated N-glycans. This study provides the first evidence that voltage-gated K+ channels Kv3.1, Kv3.3, and Kv3.4, possess distinct sialylated N-glycan structures throughout the central nervous system of the adult rat. Electrophoretic migration patterns of Kv3.1, Kv3.3, and Kv3.4 glycoproteins from spinal cord, hypothalamus, thalamus, cerebral cortex, hippocampus, and cerebellum membranes digested with glycosidases were used to identify the various glycoforms. Differences in the migration of Kv3 proteins were attributed to the desialylated N-glycans. Expression levels of the Kv3 proteins were highest in cerebellum, whereas those of Kv3.1 and Kv3.3 were much lower in the other 5 regions. The lowest level of Kv3.1 was expressed in the hypothalamus, whereas the lowest levels of Kv3.3 were expressed in both thalamus and hypothalamus. The other regions expressed intermediate levels of Kv3.3, with spinal cord expressing the highest. The expression level of Kv3.4 in the hippocampus was slightly lower than that in cerebellum, and was closely followed by the other 4 regions, with spinal cord expressing the lowest level. We suggest that novel Kv3 glycoforms may endow differences in channel function and expression among regions throughout the central nervous system.

  4. The history dependence of force production in mammalian skeletal muscle following stretch-shortening and shortening-stretch cycles.

    PubMed

    Herzog, W; Leonard, T R

    2000-05-01

    The purpose of this study was to determine the history dependence of force production during and following stretch-shortening and shortening-stretch cycles in mammalian skeletal muscle. Thirty-three different isometric, stretch, shortening, stretch-shortening and shortening-stretch experiments were preformed in cat soleus (n=8) using previously established methods. Stretch-shortening and shortening-stretch cycles are not commutative with respect to the isometric forces following the length changes. Whereas force depression following shortening is virtually unaffected by previous stretching of the muscle, force enhancement following stretch depends in a dose-dependent manner on the amount of muscle shortening preceding the stretch. The history dependence of isometric force following shortening-stretch cycles can conveniently be modelled using an elastic (compressive and tensile) element that engages at the length of muscle activation. Such an "elastic" mechanism has been proposed by Edman and Tsuchiya (1996) (Edman, K.A. P., Tsuchiya, T., 1996. Strain of passive elements during force enhancement by stretch in frog mucle fibres. Journal of Physiology 490. 1, 191-205) based on experimental observations, and has been implemented theoretically in a rheological model of muscle (Forcinito et al., 1997) (Forcinito, M., Epstein, M., Herzog, W., 1997. Theoretical considerations on myofibril stiffness. Biophysics Journal 72, 1278-1286). The history dependence of isometric force following stretch-shortening cycles appears independent of the stretch preceding the shortening, except perhaps, if stretching occurs at very high speeds (i.e. 6-10 times fibre length per second). The results of this study are hard to reconcile with the two major mechanisms associated with history dependence of force production: sarcomere length non-uniformity (Edman et al., 1993) and stress-induced cross-bridge inhibition (Maréchal and Plaghki, 1979) (Maréchal, G., Plaghki, L., 1979. The deficit of

  5. The inotropic effect of nitric oxide on mammalian papillary muscle is dependent on the level of beta1-adrenergic stimulation.

    PubMed

    Reading, S A; Barclay, J K

    2002-06-01

    We tested the hypothesis that nitric oxide has a positive inotropic effect on mammalian cardiac muscle contractility and that this effect sums with the positive inotropic effect of beta1-adrenergic agonists when both are present. Feline right ventricular papillary muscles were stimulated to contract isometrically at 0.2 Hz in Krebs-Henseleit bicarbonate buffer (KREBS) gassed with 95% O2 and 5% CO2 (26 degrees C; pH 7.34). The nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP, 10(-5) M), and the membrane permeable cGMP analog 8-bromoguanosine-3',5'-cyclophosphate sodium (Br-cGMP, 10(-5) M), significantly increased developed force by 13.3+/-1.5% (n = 11) and 7.8+/-2.8% (n = 7), respectively. SNAP, at 10(-5) M, significantly increased the force developed by papillary muscle treated with 10(-11) M or 10(-9) M dobutamine hydrochloride (a beta1-adrenergic agonist) (n = 25, 11.3+/-2.9% and 10.0+/-3.6%, respectively) when compared with the addition of KREBS (n = 27, 2.6+/-0.9% and 5.5+/-0.9%), but the increase was less than predicted by the sum of inotropic effects of SNAP and dobutamine. SNAP at 10(-5) M did not change developed force in muscles treated with 10(-7) M dobutamine but it significantly decreased developed force in muscles challenged with 10(-5) M dobutamine (n = 18, 29.3+/-5.0%) when compared with KREBS (n = 10, 41.5+/-6.8%). Similarly, 10(-4) M 8-bromo-adenosine cyclic 3',5'-hydrogen phosphate monosodium (a membrane permeable cAMP analog) increased developed force 14.9+/-3.3% and the addition of 10(-5) M Br-cGMP to those muscles significantly reduced developed force by 3.5%+/-1.1% (n = 7). Thus, the positive inotropic effect of NO decreased and ultimately became an attenuation as the level of beta1-adrenergic stimulation increased due at least in part, to an interaction between the cAMP and cGMP second messenger pathways.

  6. Dystrophin colocalizes with beta-spectrin in distinct subsarcolemmal domains in mammalian skeletal muscle

    PubMed Central

    1992-01-01

    Duchenne's muscular dystrophy (DMD) is caused by the absence or drastic decrease of the structural protein, dystrophin, and is characterized by sarcolemmal lesions in skeletal muscle due to the stress of contraction. Dystrophin has been localized to the sarcolemma, but its organization there is not known. We report immunofluorescence studies which show that dystrophin is concentrated, along with the major muscle isoform of beta-spectrin, in three distinct domains at the sarcolemma: in elements overlying both I bands and M lines, and in occasional strands running along the longitudinal axis of the myofiber. Vinculin, which has previously been found at the sarcolemma overlying the I bands and in longitudinal strands, was present in the same three structures as spectrin and dystrophin. Controls demonstrated that the labeling was intracellular. Comparison to labeling of the lipid bilayer and of the extracellular matrix showed that the labeling for spectrin and dystrophin is associated with the intact sarcolemma and is not a result of processing artifacts. Dystrophin is not required for this lattice- like organization, as similar domains containing spectrin but not dystrophin are present in muscle from the mdx mouse and from humans with Duchenne's muscular dystrophy. We discuss the possibility that dystrophin and spectrin, along with vinculin, may function to link the contractile apparatus to the sarcolemma of normal skeletal muscle. PMID:1577872

  7. Effects of H2O2 on insulin signaling the glucose transport system in mammalian skeletal muscle.

    PubMed

    Henriksen, Erik J

    2013-01-01

    Hydrogen peroxide (H2O2) is an important regulator of cellular events leading to glucose transport activation in mammalian skeletal muscle. In the absence of insulin, H2O2 in the low micromolar range engages the canonical IRS-1/PI3K/Akt-dependent insulin signaling pathway, as well as other signaling elements (AMPK and p38 MAPK), to increase basal glucose transport activity. In contrast, in the presence of insulin, H2O2 antagonizes insulin signaling by recruitment of various deleterious serine/threonine kinases, producing a state of insulin resistance. Here, we describe the H2O2 enzymatic-generating system, utilizing glucose oxidase, that has been used to investigate the impact of H2O2 on cellular signaling mechanisms related to glucose transport activity in isolated rat skeletal muscle preparations, such as the soleus. By varying the glucose oxidase concentration in the medium, target ranges of steady-state H2O2 concentrations (30-90 μM) can be attained for up to 6h, with subsequent assessment of cellular signaling and glucose transport activity.

  8. [Structural-metabolic plasticity of mammalian skeletal muscles in hypokinesis and weightlessness].

    PubMed

    Shenkman, B S

    2002-01-01

    Under review are investigations of the contractile structure of skeletal muscles of humans and animals (rats and primates) following space flight, long-term hypokinesia, immersion (human subjects) and head-down suspension (rats). Close consideration is given to experimental testing of hypotheses concerning neuronal, humoral and cell processes leading to atrophy. Described are consistencies and mechanisms of changes in the myosin phenotype and electromechanic coupling in muscular fibers as well as their capillarization and energy potential.

  9. Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats

    NASA Technical Reports Server (NTRS)

    Marsh, D. R.; Criswell, D. S.; Carson, J. A.; Booth, F. W.

    1997-01-01

    Myogenic factor mRNA expression was examined during muscle regeneration after bupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of the tibialis anterior muscle in the young rats had recovered to control values by 21 days postbupivacaine injection but in adult and old rats remained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA was significantly increased in muscles of young, adult, and old rats 5 days after bupivacaine injection. Subsequently, myogenin mRNA levels in young rat muscle decreased to postinjection control values by day 21 but did not return to control values in 28-day regenerating muscles of adult and old rats. The expression of MyoD mRNA was also increased in muscles at day 5 of regeneration in young, adult, and old rats, decreased to control levels by day 14 in young and adult rats, and remained elevated in the old rats for 28 days. In summary, either a diminished ability to downregulate myogenin and MyoD mRNAs in regenerating muscle occurs in old rat muscles, or the continuing myogenic effort includes elevated expression of these mRNAs.

  10. Diastolic scattered light fluctuation, resting force and twitch force in mammalian cardiac muscle

    PubMed Central

    Lakatta, E. G.; Lappé, D. L.

    1981-01-01

    1. When coherent light was passed through isolated isometric cardiac muscles during the diastolic or resting period, intensity fluctuations were observed in the scattered field. The frequency of these intensity fluctuations (f½) varied with many experimental interventions known to enhance Ca2+ flux into the cell. 2. In rat muscles stimulated at low frequencies (0.1 ± 2.0 min-1) stepwise increases (0.4-10 mm) of [Ca2+] in the bathing fluid ([Ca2+]e), or addition of ouabain (10-6-6 × 10-4 m) to the perfusate caused stepwise increases in f½. These were paralleled by increments in resting force (RF) such that the changes in f½ and RF were highly correlated. Substitution of K+ for Na+ in the perfusate resulted in parallel transients in RF and f½. 3. In contrast to the rat, most cat muscles stimulated at low frequencies in the steady state exhibited neither diastolic intensity fluctuations nor Ca2+-dependent changes in RF in [Ca2+]e of 10 mm or less; when [Ca2+]e was increased to 12-32 mm, however, steady-state Ca2+-dependent f½ and RF were observed. In a given [Ca2+]e reduction of [Na+]e increased f½. In the transient state following cessation of regular stimulation at more rapid rates (12-96 min-1) intensity fluctuations were present in all [Ca2+]e and decayed with time (seconds to minutes); the f½ and time course of the decay of the fluctuations were determined by the rate of prior stimulation and [Ca2+]e. 4. Maximum potentiation of twitch force in response to the above inotropic interventions was associated with an optimal level of f½ which was similar in both species; when higher levels of f½ were produced by more intense inotropic intervention, twitch force declined. Over the range of inotropic intervention up to and including that at which maximum twitch potentiation occurred, the increase in diastolic f½ predicted the extent of twitch potentiation with a high degree of accuracy (r > 0.97) both in the transient and steady states. 5. In contrast to the

  11. Possibility of leg muscle hypertrophy by ambulation in older adults: a brief review.

    PubMed

    Ozaki, Hayao; Loenneke, Jeremy P; Thiebaud, Robert S; Stager, Joel M; Abe, Takashi

    2013-01-01

    It is known that ambulatory exercises such as brisk walking and jogging are potent stimuli for improving aerobic capacity, but it is less understood whether ambulatory exercise can increase leg muscle size and function. The purpose of this brief review is to discuss whether or not ambulatory exercise elicits leg muscle hypertrophy in older adults. Daily ambulatory activity with moderate (>3 metabolic equivalents [METs], which is defined as the ratio of the work metabolic rate to the resting metabolic rate) intensity estimated by accelerometer is positively correlated with lower body muscle size and function in older adults. Although there is conflicting data on the effects of short-term training, it is possible that relatively long periods of walking, jogging, or intermittent running for over half a year can increase leg muscle size among older adults. In addition, slow-walk training with a combination of leg muscle blood flow restriction elicits muscle hypertrophy only in the blood flow restricted leg muscles. Competitive marathon running and regular high intensity distance running in young and middle-aged adults may not produce leg muscle hypertrophy due to insufficient recovery from the damaging running bout, although there have been no studies that have investigated the effects of running on leg muscle morphology in older subjects. It is clear that skeletal muscle hypertrophy can occur independently of exercise mode and load.

  12. Na,K-ATPase α2 activity in mammalian skeletal muscle T-tubules is acutely stimulated by extracellular K+.

    PubMed

    DiFranco, Marino; Hakimjavadi, Hesamedin; Lingrel, Jerry B; Heiny, Judith A

    2015-10-01

    The Na,K-ATPase α2 isoform is the predominant Na,K-ATPase in adult skeletal muscle and the sole Na,K-ATPase in the transverse tubules (T-tubules). In quiescent muscles, the α2 isozyme operates substantially below its maximal transport capacity. Unlike the α1 isoform, the α2 isoform is not required for maintaining resting ion gradients or the resting membrane potential, canonical roles of the Na,K-ATPase in most other cells. However, α2 activity is stimulated immediately upon the start of contraction and, in working muscles, its contribution is crucial to maintaining excitation and resisting fatigue. Here, we show that α2 activity is determined in part by the K+ concentration in the T-tubules, through its K+ substrate affinity. Apparent K+ affinity was determined from measurements of the K1/2 for K+ activation of pump current in intact, voltage-clamped mouse flexor digitorum brevis muscle fibers. Pump current generated by the α2 Na,K-ATPase, Ip, was identified as the outward current activated by K+ and inhibited by micromolar ouabain. Ip was outward at all potentials studied (-90 to -30 mV) and increased with depolarization in the subthreshold range, -90 to -50 mV. The Q10 was 2.1 over the range of 22-37°C. The K1/2,K of Ip was 4.3±0.3 mM at -90 mV and was relatively voltage independent. This K+ affinity is lower than that reported for other cell types but closely matches the dynamic range of extracellular K+ concentrations in the T-tubules. During muscle contraction, T-tubule luminal K+ increases in proportion to the frequency and duration of action potential firing. This K1/2,K predicts a low fractional occupancy of K+ substrate sites at the resting extracellular K+ concentration, with occupancy increasing in proportion to the frequency of membrane excitation. The stimulation of preexisting pumps by greater K+ site occupancy thus provides a rapid mechanism for increasing α2 activity in working muscles.

  13. Endothermic force generation in fast and slow mammalian (rabbit) muscle fibers.

    PubMed Central

    Ranatunga, K W

    1996-01-01

    Isometric tension responses to rapid temperature jumps (T-jumps) of 3-7 degrees C were examined in single skinned fibers isolated from rabbit psoas (fast) and soleus (slow) muscles. T-jumps were induced by an infrared laser pulse (wavelength 1.32 microns, pulse duration 0.2 ms) obtained from a Nd-YAG laser, which heated the fiber and bathing buffer solution in a 50-microliter trough. After a T-jump, the temperature near the fiber remained constant for approximately 0.5 s, and the temperature could be clamped for longer periods by means of Peltier units assembled on the back trough wall. A T-jump produced a step decrease in tension in both fast and slow muscle fibers in rigor, indicating thermal expansion. In maximally Ca-activated (pCa approximately 4) fibers, the increase of steady tension with heating (3-35 degrees C) was approximately sigmoidal, and a T-jump at any temperature induced a more complex tension transient than in rigor fibers. An initial (small amplitude) step decrease in tension followed by a rapid recovery (tau(1); see Davis and Harrington, 1993) was seen in some records from both fiber types, which presumably was an indirect consequence of thermal expansion. The net rise in tension after a T-jump was biexponential, and its time course was characteristically different in the two fibers. At approximately 12 degrees C the reciprocal time constants for the two exponential components (tau(2) and tau(3), respectively, were approximately 70.s(-1) and approximately 15.s(-1) in fast fibers and approximately 20.s(-1) and approximately 3.s(-1) in slow fibers. In both fibers, tau(2) ("endothermic force regeneration") became faster with an increase in temperature. Furthermore, tau(3) was temperature sensitive in slow fibers but not in fast fibers. The results are compared and contrasted with previous findings from T-jump experiments on fast fibers. It is observed that the fast/slow fiber difference in the rate of endothermic force generation (three- to

  14. Effect of postnatal development on calcium currents and slow charge movement in mammalian skeletal muscle

    PubMed Central

    Beam, KG; Knudson, CM

    1988-01-01

    Single- (whole-cell patch) and two-electrode voltage-clamp techniques were used to measure transient (Ifast) and sustained (Islow) calcium currents, linear capacitance, and slow, voltage-dependent charge movements in freshly dissociated fibers of the flexor digitorum brevis (FDB) muscle of rats of various postnatal ages. Peak Ifast was largest in FDB fibers of neonatal (1-5 d) rats, having a magnitude in 10 mM external Ca of 1.4 +/- 0.9 pA/pF (mean +/- SD; current normalized by linear fiber capacitance). Peak Ifast was smaller in FDB fibers of older animals, and by approximately 3 wk postnatal, it was so small as to be unmeasurable. By contrast, the magnitudes of Islow and charge movement increased substantially during postnatal development. Peak Islow was 3.6 +/- 2.5 pA/pF in FDB fibers of 1-5-d rats and increased to 16.4 +/- 6.5 pA/pF in 45-50-d-old rats; for these same two age groups, Qmax, the total mobile charge measurable as charge movement, was 6.0 +/- 1.7 and 23.8 +/- 4.0 nC/microF, respectively. As both Islow and charge movement are thought to arise in the transverse-tubular system, linear capacitance normalized by the area of fiber surface was determined as an indirect measure of the membrane area of the t-system relative to that of the fiber surface. This parameter increased from 1.5 +/- 0.2 microF/cm2 in 2-d fibers to 2.9 +/- 0.4 microF/cm2 in 44-d fibers. The increases in peak Islow, Qmax, and normalized linear capacitance all had similar time courses. Although the function of Islow is unknown, the substantial postnatal increase in its magnitude suggests that it plays an important role in the physiology of skeletal muscle. PMID:2458430

  15. [The role of the psoas muscle: apropos of the dissection of the muscles from 10 adults and 10 newborn infants].

    PubMed

    Le Floch-Prigent, P

    1983-06-01

    The action of the iliopsoas muscle (Musculus iliopsoas) on movements of the hip is studied by direct traction on fresh cadavers (10 still-born and 10 adults). The psoas muscle is a powerful flexor of the hip but also an external rotator. The action of external rotation is moderate but obvious in every position of the femur (Os femoris) and more important if previously in abduction and internal rotation.

  16. Muscle performance and physical function are associated with voluntary rate of neuromuscular activation in older adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Participants were recruited to three experimental groups: middle-aged healthy adults (MH), older healthy adults (OH), and older adults with mobility limitations (OML). OH and OML were primarily differentiated by performance on the Short Physical Performance Battery (SPPB). Muscle performance (accele...

  17. OnabotulinumtoxinA muscle injection patterns in adult spasticity: a systematic literature review

    PubMed Central

    2013-01-01

    Background OnabotulinumtoxinA has demonstrated significant benefit in adult focal spasticity. This study reviews the injection patterns (i.e., muscle distribution, dosing) of onabotulinumtoxinA for treatment of adult spasticity, as reported in published studies. Methods A systematic review of clinical trials and observational studies published between 1990 and 2011 reporting data on muscles injected with onabotulinumtoxinA in adult patients treated for any cause of spasticity. Results 28 randomized, 5 nonrandomized, and 37 single-arm studies evaluating 2,163 adult patients were included. The most frequently injected upper-limb muscles were flexor carpi radialis (64.0% of patients), flexor carpi ulnaris (59.1%), flexor digitorum superficialis (57.2%), flexor digitorum profundus (52.5%), and biceps brachii (38.8%). The most frequently injected lower-limb muscles were the gastrocnemius (66.1% of patients), soleus (54.7%), and tibialis posterior (50.5%). The overall dose range reported was 5–200 U for upper-limb muscles and 10–400 U for lower-limb muscles. Conclusions The reviewed evidence indicates that the muscles most frequently injected with onabotulinumtoxinA in adults with spasticity were the wrist, elbow, and finger flexors and the ankle plantar flexors. OnabotulinumtoxinA was injected over a broad range of doses per muscle among the studies included in this review, but individual practitioners should be mindful of local regulatory approvals and regulations. PMID:24011236

  18. Enzyme immunoassay and proteomic characterization of troponin I as a marker of mammalian muscle compounds in raw meat and some meat products.

    PubMed

    Zvereva, Elena A; Kovalev, Leonid I; Ivanov, Alexei V; Kovaleva, Marina A; Zherdev, Anatoly V; Shishkin, Sergey S; Lisitsyn, Andrey B; Chernukha, Irina M; Dzantiev, Boris B

    2015-07-01

    The skeletal muscle protein troponin I (TnI) has been characterized as a potential thermally stable and species-specific biomarker of mammalian muscle tissues in raw meat and meat products. This study proposed a technique for the quantification of TnI comprising protein extraction and sandwich enzyme-linked immunosorbent assay (ELISA). The technique is characterized by a TnI detection limit of 4.8 ng/ml with quantifiable concentrations ranging from 8.7 to 52 ng/ml. The method was shown to be suitable for detection of TnI in mammalian (beef, pork, lamb, and horse) meat but not in poultry (chicken, turkey, and duck) meat. In particular, the TnI content in beef was 0.40 3 ± 0.058 mg/g of wet tissue. The TnI estimations obtained for the pork and beef samples using ELISA were comparable to the proteomic analysis results. Thus, the quantitative study of TnI can be a convenient way to assess the mammalian muscle tissue content of various meat products.

  19. Mechanism of potassium efflux and action potential shortening during ischaemia in isolated mammalian cardiac muscle.

    PubMed Central

    Gasser, R N; Vaughan-Jones, R D

    1990-01-01

    1. Ischaemia was simulated in the isolated sheep cardiac Purkinje fibre and guinea-pig papillary muscle by immersing the preparations in paraffin oil. Ion-selective microelectrodes recorded potassium (Ks+) and pH (pHs) in the thin film of Tyrode solution trapped at the fibre surface while other microelectrodes recorded intracellular pH (pHi), membrane potential and action potentials (AP) (evoked by field stimulation), or membrane current (two-microelectrode voltage clamp in shortened Purkinje fibres). Twitch tension was also monitored. The paraffin oil model reproduced the salient characteristics of myocardial ischaemia, i.e. a decrease of twitch tension; a decrease of pHi and pHs; a rise in Ks+ (by 2-3 mM); a depolarization of diastolic membrane potential; considerable shortening of the AP (up to 30% within 4 min). 2. The sulphonylurea compounds, glibenclamide (200 microM) and tolbutamide (1 mM), known inhibitors of the KATP channel, completely blocked the ischaemic rise of Ks+ and prevented AP shortening. Ischaemic tension decline was notably less pronounced in the presence of sulphonylureas. 3. The ischaemic increase of slope conductance (Purkinje fibre) was prevented by 1 mM-tolbutamide and 200 microM-glibenclamide. 4. Sulphonylureas did not affect resting membrane potential, the AP or the current-voltage relationship under non-ischaemic conditions (this also indicates that ischaemic Ks+ accumulation is not fuelled by the background K+ current [iK1] which was shown, as expected, to be Ba2+ sensitive). 5. In a normally perfused preparation, reducing intracellular ATP by inhibiting glycolysis with 2-deoxyglucose (DOG) produced a similar AP shortening plus a membrane hyperpolarization, both of which were inhibited by tolbutamide or glibenclamide. The AP shortening was not related uniquely to the fall of pHi observed under these conditions since experimentally reducing pHi (by reducing pHo in the absence of DOG) lengthened rather than shortened the AP. 6. The

  20. Adult stem cells and mammalian epimorphic regeneration-insights from studying annual renewal of deer antlers.

    PubMed

    Li, Chunyi; Yang, Fuhe; Sheppard, Allan

    2009-09-01

    Mammalian organ regeneration is the "Holy Grail" of modern regenerative biology and medicine. The most dramatic organ replacement is known as epimorphic regeneration. To date our knowledge of epimorphic regeneration has come from studies of amphibians. Notably, these animals have the ability to reprogram phenotypically committed cells at the amputation plane toward an embryonic-like cell phenotype (dedifferentiation). The capability of mammals to initiate analogous regeneration, and whether similar mechanisms would be involved if it were to occur, remain unclear. Deer antlers are the only mammalian appendages capable of full renewal, and therefore offer a unique opportunity to explore how nature has solved the problem of mammalian epimorphic regeneration. Following casting of old hard antlers, new antlers regenerate from permanent bony protuberances, known as pedicles. Studies through morphological and histological examinations, tissue deletion and transplantation, and cellular and molecular techniques have demonstrated that antler renewal is markedly different from that of amphibian limb regeneration (dedifferentiation-based), being a stem cell-based epimorphic process. Antler stem cells reside in the pedicle periosteum. We envisage that epimorphic regeneration of mammalian appendages, other than antler, could be made possible by recreating comparable milieu to that which supports the elaboration of that structure from the pedicle periosteum.

  1. Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function

    PubMed Central

    Garza-Lombó, Carla; Gonsebatt, María E.

    2016-01-01

    The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

  2. The electrophysiology of the olfactory-hippocampal circuit in the isolated and perfused adult mammalian brain in vitro.

    PubMed

    de Curtis, M; Paré, D; Llinás, R R

    1991-10-01

    The viability and general electrophysiological properties of the limbic system in the adult mammalian brain isolated and maintained in vitro by arterial perfusion are described. The isolated brain preparation combines the advantages of intact synaptic connectivity and accessibility of different areas of the encephalic mass with those of the in vitro approach, i.e., stability and control of the ionic environment. Extracellular field potential as well as intracellular recordings were performed at different levels in the limbic system of isolated adult guinea pig brains. The results demonstrate that in the piriform, entorhinal, and hippocampal cortices, the intrinsic electrical properties of individual cells as well as the spontaneous and evoked electrical activity in the neuronal ensembles they comprise, were virtually identical to those observed in vivo. The properties of the limbic system loop were determined.

  3. Platelet-derived growth factor regulates vascular smooth muscle phenotype via mammalian target of rapamycin complex 1

    SciTech Connect

    Ha, Jung Min; Yun, Sung Ji; Kim, Young Whan; Jin, Seo Yeon; Lee, Hye Sun; Song, Sang Heon; Shin, Hwa Kyoung; Bae, Sun Sik

    2015-08-14

    Mammalian target of rapamycin complex (mTORC) regulates various cellular processes including proliferation, growth, migration and differentiation. In this study, we showed that mTORC1 regulates platelet-derived growth factor (PDGF)-induced phenotypic conversion of vascular smooth muscle cells (VSMCs). Stimulation of contractile VSMCs with PDGF significantly reduced the expression of contractile marker proteins in a time- and dose-dependent manner. In addition, angiotensin II (AngII)-induced contraction of VSMCs was completely blocked by the stimulation of VSMCs with PDGF. PDGF-dependent suppression of VSMC marker gene expression was significantly blocked by inhibition of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), and mTOR whereas inhibition of p38 MAPK had no effect. In particular, inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked the PDGF-dependent phenotypic change of VSMCs whereas silencing of Rictor had no effect. In addition, loss of AngII-dependent contraction by PDGF was significantly retained by silencing of Raptor. Inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked PDGF-induced proliferation of VSMCs. Taken together, we suggest that mTORC1 plays an essential role in PDGF-dependent phenotypic changes of VSMCs. - Graphical abstract: Regulation of VSMC phenotype by PDGF-dependent activation of mTORC1. - Highlights: • The expression of contractile marker proteins was reduced by PDGF stimulation. • PDGF-dependent phenotypic conversion of VSMCs was blocked by inhibition of mTOR. • PDGF-induced proliferation of VSMCs was attenuated by inhibition of mTORC1. • mTORC1 plays a critical role in PDGF-dependent phenotypic conversion of VSMCs.

  4. Effect of Loquat Leaf Extract on Muscle Strength, Muscle Mass, and Muscle Function in Healthy Adults: A Randomized, Double-Blinded, and Placebo-Controlled Trial

    PubMed Central

    Choe, Sangmin; Lee, Chang-Hyung; Shin, Jin-Hong

    2016-01-01

    Ursolic acid (UA) is the major active component of the loquat leaf extract (LLE) and several previous studies have indicated that UA may have the ability to prevent skeletal muscle atrophy. Therefore, we conducted a randomized, double-blind, and placebo-controlled study to investigate the effects of the LLE on muscle strength, muscle mass, muscle function, and metabolic markers in healthy adults; the safety of the compound was also evaluated. We examined the peak torque/body weight at 60°/s knee extension, handgrip strength, skeletal muscle mass, physical performance, and metabolic parameters at baseline, as well as after 4 and 12 weeks of intervention. Either 500 mg of LLE (50.94 mg of UA) or a placebo was administered to fifty-four healthy adults each day for 12 weeks; no differences in muscle strength, muscle mass, and physical performance were observed between the two groups. However, the right-handgrip strength of female subjects in the LLE group was found to be significantly better than that of subjects in the control group (P = 0.047). Further studies are required to determine the optimal dose and duration of LLE supplementation to confirm the first-stage study results for clinical application. ClinicalTrials.gov Identifier is NCT02401113. PMID:27999607

  5. The effect of superficial trunk muscle exercise and deep trunk muscle exercise on the foot pressure of healthy adults

    PubMed Central

    Kim, Suzy; Shim, Jemyung; Kim, Sungjoong; Namkoong, Seung; Kim, Hwanhee

    2015-01-01

    [Purpose] The purpose of this study was to analyze the effect of superficial trunk muscle exercise and deep trunk muscle exercise on the foot pressure of healthy adults. [Subjects] The subjects were 30 healthy females and males who agreed to participate in this study. There were two groups, a superficial trunk muscle exercise group and a deep trunk muscle exercise group, with 15 participants in each. [Methods] The exercises were conducted 5 times a week for 4 weeks for both groups. A gait analyzer was used to measure foot plantar pressure while walking on a plate. Participants were measured before starting the exercise and after 4 weeks. The paired t-test was used to analyze the pre-and post-test results. [Results] There were no significant differences in foot pressure in any region in the superficial trunk muscle exercise group. In the deep trunk muscle exercise group, there were statistically significant increase in F1, F4, F5, R1 and R3. In addition, there were significant decreases in R2 and R4. [Conclusion] After the 4-week deep trunk muscle exercise group decreases in foot pressure on the inner foot and increases on the outside of the feet indicate normal and overall even distribution of body weight on the feet. PMID:25931714

  6. Mammalian target of rapamycin complex 1 activation is required for the stimulation of human skeletal muscle protein synthesis by essential amino acids.

    PubMed

    Dickinson, Jared M; Fry, Christopher S; Drummond, Micah J; Gundermann, David M; Walker, Dillon K; Glynn, Erin L; Timmerman, Kyle L; Dhanani, Shaheen; Volpi, Elena; Rasmussen, Blake B

    2011-05-01

    The relationship between mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis during instances of amino acid surplus in humans is based solely on correlational data. Therefore, the goal of this study was to use a mechanistic approach specifically designed to determine whether increased mTORC1 activation is requisite for the stimulation of muscle protein synthesis following L-essential amino acid (EAA) ingestion in humans. Examination of muscle protein synthesis and signaling were performed on vastus lateralis muscle biopsies obtained from 8 young (25 ± 2 y) individuals who were studied prior to and following ingestion of 10 g of EAA during 2 separate trials in a randomized, counterbalanced design. The trials were identical except during 1 trial, participants were administered a single oral dose of a potent mTORC1 inhibitor (rapamycin) prior to EAA ingestion. In response to EAA ingestion, an ~60% increase in muscle protein synthesis was observed during the control trial, concomitant with increased phosphorylation of mTOR (Ser(2448)), ribosomal S6 kinase 1 (Thr(389)), and eukaryotic initiation factor 4E binding protein 1 (Thr(37/46)). In contrast, prior administration of rapamycin completely blocked the increase in muscle protein synthesis and blocked or attenuated activation of mTORC1-signaling proteins. The inhibition of muscle protein synthesis and signaling was not due to differences in either extracellular or intracellular amino acid availability, because these variables were similar between trials. These data support a fundamental role for mTORC1 activation as a key regulator of human muscle protein synthesis in response to increased EAA availability. This information will be useful in the development of evidence-based nutritional therapies targeting mTORC1 to counteract muscle wasting associated with numerous clinical conditions.

  7. EFFECTS OF AGE AND ACUTE MUSCLE FATIGUE ON REACTIVE POSTURAL CONTROL IN HEALTHY ADULTS

    PubMed Central

    Papa, Evan V.; Foreman, K. Bo; Dibble, Lee E.

    2015-01-01

    BACKGROUND Falls can cause moderate to severe injuries such as hip fractures and head trauma in older adults. While declines in muscle strength and sensory function contribute to increased falls in older adults, skeletal muscle fatigue is often overlooked as an additional contributor to fall risk. The purpose of this investigation was to examine the effects of acute lower extremity muscle fatigue and age on reactive postural control in healthy adults. METHODS A sample of 16 individuals participated in this study (8 healthy older adults and 8 healthy young persons). Whole body kinematic and kinetic data were collected during anterior and posterior reproducible fall tests before (T0) and immediately after (T1) eccentric muscle fatiguing exercise, as well as after 15-minutes (T15) and 30-minutes (T30) of rest. FINDINGS Lower extremity joint kinematics of the stepping limb during the support (landing) phase of the anterior fall were significantly altered by the presence of acute muscle fatigue. Step velocity was significantly decreased during the anterior falls. Statistically significant main effects of age were found for step length in both fall directions. Effect sizes for all outcomes were small. No statistically significant interaction effects were found. INTERPRETATION Muscle fatigue has a measurable effect on lower extremity joint kinematics during simulated falls. These alterations appear to resolve within 15 minutes of recovery. The above deficits, coupled with a reduced step length, may help explain the increased fall risk in older adults. PMID:26351001

  8. Muscle regeneration by adipose tissue-derived adult stem cells attached to injectable PLGA spheres.

    PubMed

    Kim, MiJung; Choi, Yu Suk; Yang, Seung Hye; Hong, Hea-Nam; Cho, Sung-Woo; Cha, Sang Myun; Pak, Jhang Ho; Kim, Chan Wha; Kwon, Seog Woon; Park, Chan Jeoung

    2006-09-22

    The [corrected] use of adult stem cells for cell-based tissue engineering and regeneration strategies represents a promising approach for skeletal muscle repair. We have evaluated the combination of adipose tissue-derived adult stem cells (ADSCs) obtained from autologous liposuction and injectable poly(lactic-co-glycolic acid) (PLGA) spheres for muscle regeneration. ADSCs attached to PLGA spheres and PLGA spheres alone were cultured in myogenic medium for 21 days and injected subcutaneously into the necks of nude mice. After 30 and 60 days, the mice were sacrificed, and newly formed tissues were analyzed by immunostaining, H and E staining, and RT-PCR. We found that ADSCs attached to PLGA spheres, but not PLGA spheres alone, were able to generate muscle tissue. These findings suggest that ADSCs and PLGA spheres are useful materials for muscle tissue engineering and that their combination can be used in clinical settings for muscle regeneration.

  9. Do muscle mass, muscle density, strength and physical function similarly influence risk of hospitalization in older adults?

    PubMed Central

    Cawthon, Peggy Mannen; Fox, Kathleen M.; Gandra, Shravanthi. R.; Delmonico, Matthew J.; Chiou, Chiun-Fang; Anthony, Mary S.; Sewall, Ase; Goodpaster, Bret; Satterfield, Suzanne; Cummings, Steven R.; Harris, Tamara B.

    2012-01-01

    Objectives To examine the association between strength, function, lean mass, muscle density and risk of hospitalization. Design Prospective cohort stud Setting Two U.S. clinical centers Participants Adults aged 70 – 80 years (N=3,011) from the Health, Aging and Body Composition Study. Measurements Measures included grip strength; knee extension strength; lean mass; walking speed; chair stand pace. Thigh computed tomography scans assessed muscle area and density (a proxy for muscle fat infiltration). Hospitalizations were confirmed by local review of medical records. Negative binomial regression models estimated incident rate ratios (IRRs) of hospitalization for race/sex specific quartiles of each muscle/function parameter separately. Multivariate models adjusted for age, body mass index, health status and coexisting medical conditions. Results During an average 4.7 years of follow-up, 1,678 (55.7%) participants experienced ≥1 hospitalization. Participants in the lowest quartile of muscle density were more likely to be subsequently hospitalized (multivariate IRR: 1.47, 95% CI: 1.24, 1.73) compared to the highest quartile. Similarly, participants with the weakest grip strength were at increased risk of hospitalization (MIRR: 1.52, 95% CI: 1.30, 1.78, Q1 vs. Q4). Comparable results were seen for knee strength, walking pace and chair stands pace. Lean mass and muscle area were not associated with risk of hospitalization. Conclusion Weak strength, poor function and low muscle density, but not muscle size or lean mass, were associated with an increased risk of hospitalization. Interventions to reduce the disease burden associated with sarcopenia should focus on increasing muscle strength and improving physical function rather than simply increasing lean mass. PMID:19682143

  10. Motor activity affects adult skeletal muscle re-innervation acting via tyrosine kinase receptors.

    PubMed

    Sartini, Stefano; Bartolini, Fanny; Ambrogini, Patrizia; Betti, Michele; Ciuffoli, Stefano; Lattanzi, Davide; Di Palma, Michael; Cuppini, Riccardo

    2013-05-01

    Recently, muscle expression of brain-derived neurotrophic factor (BDNF) mRNA and protein under activity control has been reported. BDNF is a neurotrophin known to be involved in axon sprouting in the CNS. Hence, we set out to study the effect of chronic treadmill mid-intensity running on adult rat muscle re-innervation, and to explore the involvement of BDNF and tropomyosin-related kinase (Trk) receptors. After nerve crush, muscle re-innervation was evaluated using intracellular recordings, tension recordings, immunostaining and Western blot analyses. An enhanced muscle multiple innervation was found in running rats that was fully reversed to control values blocking Trk receptors or interrupting the running activity. An increase in muscle multiple innervation was also found in sedentary rats treated with a selective TrkB receptor agonist. The expression of TrkB receptors by intramuscular axons was demonstrated, and increased muscle expression of BDNF was found in running animals. The increase in muscle multiple innervation was consistent with the faster muscle re-innervation that we found in running animals. We conclude that, when regenerating axons contact muscle cells, muscle activity progressively increases modulating BDNF and possibly other growth factors, which in turn, acting via Trk receptors, induce axon sprouting to re-innervate skeletal muscle.

  11. Delayed Onset Muscle Soreness After Inspiratory Threshold Loading in Healthy Adults

    PubMed Central

    Mathur, Sunita; Sheel, A. William; Road, Jeremy D.; Reid, W. Darlene

    2010-01-01

    Purpose: Skeletal muscle damage occurs following high-intensity or unaccustomed exercise; however, it is difficult to monitor damage to the respiratory muscles, particularly in humans. The aim of this study was to use clinical measures to investigate the presence of skeletal muscle damage in the inspiratory muscles. Methods: Ten healthy subjects underwent 60 minutes of voluntary inspiratory threshold loading (ITL) at 70% of maximal inspiratory pressure. Maximal inspiratory and expiratory mouth pressures, delayed onset muscle soreness on a visual analogue scale and plasma creatine kinase were measured prior to ITL, and at repeated time points after ITL (4, 24 and 48 hours post-ITL). Results: Delayed onset muscle soreness was present in all subjects 24 hours following ITL (intensity = 22 ± 6 mm; significantly higher than baseline p = 0.02). Muscle soreness was reported primarily in the anterior neck region, and was correlated to the amount of work done by the inspiratory muscles during ITL (r = 0.72, p = 0.02). However, no significant change was observed in maximal inspiratory or expiratory pressures or creatine kinase. Conclusions: These findings suggest that an intense bout of ITL results in muscle soreness primarily in the accessory muscles of inspiration, however, may be insufficient to cause significant muscle damage in healthy adults. PMID:20467514

  12. Relationships between metabolic rate, muscle electromyograms, and swim performance of adult chinook salmon

    SciTech Connect

    Geist, David R. ); Brown, Richard S. ); Cullinan, Valerie I. ); Mesa, Matthew G.; VanderKooi, S P.; McKinstry, Craig A. )

    2003-10-01

    We measured oxygen consumption rates of adult spring Chinook salmon and compared these values to other species of Pacific salmon. Our results indicated that adult salmon achieve their maximum level of oxygen consumption at about their upper critical swim speed. It is also at this speed that the majority of the energy supplied to the swimming fish switches from red muscle (powered by aerobic metabolism) to white muscle (powered by anaerobic metabolism). Determining the swimming performance of adult salmon will assist managers in developing fishways and other means to safely pass fish over hydroelectric dams and other man-made structures.

  13. Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration.

    PubMed

    Sambasivan, Ramkumar; Yao, Roseline; Kissenpfennig, Adrien; Van Wittenberghe, Laetitia; Paldi, Andràs; Gayraud-Morel, Barbara; Guenou, Hind; Malissen, Bernard; Tajbakhsh, Shahragim; Galy, Anne

    2011-09-01

    Distinct cell populations with regenerative capacity have been reported to contribute to myofibres after skeletal muscle injury, including non-satellite cells as well as myogenic satellite cells. However, the relative contribution of these distinct cell types to skeletal muscle repair and homeostasis and the identity of adult muscle stem cells remain unknown. We generated a model for the conditional depletion of satellite cells by expressing a human diphtheria toxin receptor under control of the murine Pax7 locus. Intramuscular injection of diphtheria toxin during muscle homeostasis, or combined with muscle injury caused by myotoxins or exercise, led to a marked loss of muscle tissue and failure to regenerate skeletal muscle. Moreover, the muscle tissue became infiltrated by inflammatory cells and adipocytes. This localised loss of satellite cells was not compensated for endogenously by other cell types, but muscle regeneration was rescued after transplantation of adult Pax7(+) satellite cells alone. These findings indicate that other cell types with regenerative potential depend on the presence of the satellite cell population, and these observations have important implications for myopathic conditions and stem cell-based therapeutic approaches.

  14. Effects of a myosin-II inhibitor (N-benzyl-p-toluene sulphonamide, BTS) on contractile characteristics of intact fast-twitch mammalian muscle fibres.

    PubMed

    Pinniger, G J; Bruton, J D; Westerblad, H; Ranatunga, K W

    2005-01-01

    We have examined the effects of N-benzyl-p-toluene sulphonamide (BTS), a potent and specific inhibitor of fast muscle myosin-II, using small bundles of intact fibres or single fibres from rat foot muscle. BTS decreased tetanic tension reversibly in a concentration-dependent manner with half-maximal inhibition at approximately approximately 2 microM at 20 degrees C. The inhibition of tension with 10 microM BTS was marked at the three temperatures examined (10, 20 and 30 degrees C), but greatest at 10 degrees C. BTS decreased active muscle stiffness to a lesser extent than tetanic tension indicating that not all of the tension inhibition was due to a reduced number of attached cross-bridges. BTS-induced inhibition of active tension was not accompanied by any change in the free myoplasmic Ca2+ transients. The potency and specificity of BTS make it a very suitable myosin inhibitor for intact mammalian fast muscle and should be a useful tool for the examination of outstanding questions in muscle contraction.

  15. A treadmill exercise reactivates the signaling of the mammalian target of rapamycin (mTor) in the skeletal muscles of starved mice.

    PubMed

    Zheng, Dong-Mei; Bian, Zehua; Furuya, Norihiko; Oliva Trejo, Juan Alejandro; Takeda-Ezaki, Mitsue; Takahashi, Katsuyuki; Hiraoka, Yuka; Mineki, Reiko; Taka, Hikari; Ikeda, Shin-Ichi; Komatsu, Masaaki; Fujimura, Tsutomu; Ueno, Takashi; Ezaki, Junji

    2015-01-02

    It has been well established that a starvation-induced decrease in insulin/IGF-I and serum amino acids effectively suppresses the mammalian target of rapamycin (mTor) signaling to induce autophagy, which is a major degradative cellular pathway in skeletal muscles. In this study, we investigated the systematic effects of exercise on the mTor signaling of skeletal muscles. Wild type C57BL/6J mice were starved for 24h under synchronous autophagy induction conditions. Under these conditions, endogenous LC3-II increased, while both S6-kinse and S6 ribosomal protein were dephosphorylated in the skeletal muscles, which indicated mTor inactivation. Using GFP-LC3 transgenic mice, it was also confirmed that fluorescent GFP-LC3 dots in the skeletal muscles increased, including soleus, plantaris, and gastrocnemius, which clearly showed autophagosomal induction. These starved mice were then subjected to a single bout of running on a treadmill (12m/min, 2h, with a lean of 10 degrees). Surprisingly, biochemical analyses revealed that the exercise elicited a decrease in the LC3-II/LC3-I ratio as well as an inversion from the dephosphorylated state to the rephosphorylated state of S6-kinase and ribosomal S6 in these skeletal muscles. Consistently, the GFP-LC3 dots of the skeletal muscles were diminished immediately after the exercise. These results indicated that exercise suppressed starvation-induced autophagy through a reactivation of mTor signaling in the skeletal muscles of these starved mice.

  16. Proprioceptive acuity predicts muscle co-contraction of the tibialis anterior and gastrocnemius medialis in older adults' dynamic postural control.

    PubMed

    Craig, C E; Goble, D J; Doumas, M

    2016-05-13

    Older adults use a different muscle strategy to cope with postural instability, in which they 'co-contract' the muscles around the ankle joint. It has been suggested that this is a compensatory response to age-related proprioceptive decline however this view has never been assessed directly. The current study investigated the association between proprioceptive acuity and muscle co-contraction in older adults. We compared muscle activity, by recording surface electromyography (EMG) from the bilateral tibialis anterior (TA) and gastrocnemius medialis (GM) muscles, in young (aged 18-34) and older adults (aged 65-82) during postural assessment on a fixed and sway-referenced surface at age-equivalent levels of sway. We performed correlations between muscle activity and proprioceptive acuity, which was assessed using an active contralateral matching task. Despite successfully inducing similar levels of sway in the two age groups, older adults still showed higher muscle co-contraction. A stepwise regression analysis showed that proprioceptive acuity measured using variable error was the best predictor of muscle co-contraction in older adults. However, despite suggestions from previous research, proprioceptive error and muscle co-contraction were negatively correlated in older adults, suggesting that better proprioceptive acuity predicts more co-contraction. Overall, these results suggest that although muscle co-contraction may be an age-specific strategy used by older adults, it is not to compensate for age-related proprioceptive deficits.

  17. Characterization of muscle spindle afferents in the adult mouse using an in vitro muscle-nerve preparation.

    PubMed

    Wilkinson, Katherine A; Kloefkorn, Heidi E; Hochman, Shawn

    2012-01-01

    We utilized an in vitro adult mouse extensor digitorum longus (EDL) nerve-attached preparation to characterize the responses of muscle spindle afferents to ramp-and-hold stretch and sinusoidal vibratory stimuli. Responses were measured at both room (24°C) and muscle body temperature (34°C). Muscle spindle afferent static firing frequencies increased linearly in response to increasing stretch lengths to accurately encode the magnitude of muscle stretch (tested at 2.5%, 5% and 7.5% of resting length [Lo]). Peak firing frequency increased with ramp speeds (20% Lo/sec, 40% Lo/sec, and 60% Lo/sec). As a population, muscle spindle afferents could entrain 1:1 to sinusoidal vibrations throughout the frequency (10-100 Hz) and amplitude ranges tested (5-100 µm). Most units preferentially entrained to vibration frequencies close to their baseline steady-state firing frequencies. Cooling the muscle to 24°C decreased baseline firing frequency and units correspondingly entrained to slower frequency vibrations. The ramp component of stretch generated dynamic firing responses. These responses and related measures of dynamic sensitivity were not able to categorize units as primary (group Ia) or secondary (group II) even when tested with more extreme length changes (10% Lo). We conclude that the population of spindle afferents combines to encode stretch in a smoothly graded manner over the physiological range of lengths and speeds tested. Overall, spindle afferent response properties were comparable to those seen in other species, supporting subsequent use of the mouse genetic model system for studies on spindle function and dysfunction in an isolated muscle-nerve preparation.

  18. A Twist2-dependent progenitor cell contributes to adult skeletal muscle.

    PubMed

    Liu, Ning; Garry, Glynnis A; Li, Stephen; Bezprozvannaya, Svetlana; Sanchez-Ortiz, Efrain; Chen, Beibei; Shelton, John M; Jaichander, Priscilla; Bassel-Duby, Rhonda; Olson, Eric N

    2017-03-01

    Skeletal muscle possesses remarkable regenerative potential due to satellite cells, an injury-responsive stem cell population located beneath the muscle basal lamina that expresses Pax7. By lineage tracing of progenitor cells expressing the Twist2 (Tw2) transcription factor in mice, we discovered a myogenic lineage that resides outside the basal lamina of adult skeletal muscle. Tw2(+) progenitors are molecularly and anatomically distinct from satellite cells, are highly myogenic in vitro, and can fuse with themselves and with satellite cells. Tw2(+) progenitors contribute specifically to type IIb/x myofibres during adulthood and muscle regeneration, and their genetic ablation causes wasting of type IIb myofibres. We show that Tw2 expression maintains progenitor cells in an undifferentiated state that is poised to initiate myogenesis in response to appropriate cues that extinguish Tw2 expression. Tw2-expressing myogenic progenitors represent a previously unrecognized, fibre-type-specific stem cell involved in postnatal muscle growth and regeneration.

  19. Muscle Stem Cells: A Model System for Adult Stem Cell Biology.

    PubMed

    Cornelison, Ddw; Perdiguero, Eusebio

    2017-01-01

    Skeletal muscle stem cells, originally termed satellite cells for their position adjacent to differentiated muscle fibers, are absolutely required for the process of skeletal muscle repair and regeneration. In the last decade, satellite cells have become one of the most studied adult stem cell systems and have emerged as a standard model not only in the field of stem cell-driven tissue regeneration but also in stem cell dysfunction and aging. Here, we provide background in the field and discuss recent advances in our understanding of muscle stem cell function and dysfunction, particularly in the case of aging, and the potential involvement of muscle stem cells in genetic diseases such as the muscular dystrophies.

  20. Altered activation of the antagonist muscle during practice compromises motor learning in older adults.

    PubMed

    Chen, Yen-Ting; Kwon, MinHyuk; Fox, Emily J; Christou, Evangelos A

    2014-08-15

    Aging impairs the activation of muscle; however, it remains unclear whether it contributes to deficits in motor learning in older adults. The purpose of this study was to determine whether altered activation of antagonistic muscles in older adults during practice inhibits their ability to transfer a motor task ipsilaterally. Twenty young (25.1 ± 3.9 yr; 10 men, 10 women) and twenty older adults (71.5 ± 4.8 yr; 10 men, 10 women) participated. Half of the subjects practiced 100 trials of a rapid goal-directed task with ankle dorsiflexion and were tested 1 day later with elbow flexion (transfer). The rest did not perform any ankle practice and only performed the task with elbow flexion. The goal-directed task consisted of rapid movement (180 ms) to match a spatiotemporal target. For each limb, we recorded the EMG burst activity of the primary agonist and antagonist muscles. The rate of improvement during task acquisition (practice) was similar for young and older adults (P > 0.3). In contrast, only young adults were able to transfer the task to the upper limb. Specifically, young adults who practiced ankle dorsiflexion exhibited ∼30% (P < 0.05) lower movement error and ∼60% (P < 0.05) lower antagonist EMG burst activity compared with older adults who received equal practice and young adults who did not receive any ankle dorsiflexion practice. These results provide novel evidence that the deficient motor learning in older adults may be related to a differential activation of the antagonist muscle, which compromises their ability to acquire the task during practice.

  1. Synergist Ablation as a Rodent Model to Study Satellite Cell Dynamics in Adult Skeletal Muscle.

    PubMed

    Kirby, Tyler J; McCarthy, John J; Peterson, Charlotte A; Fry, Christopher S

    2016-01-01

    In adult skeletal muscles, satellite cells are the primary myogenic stem cells involved in myogenesis. Normally, they remain in a quiescent state until activated by a stimulus, after which they proliferate, differentiate, and fuse into an existing myofiber or form a de novo myofiber. To study satellite cell dynamics in adult murine models, most studies utilize regeneration models in which the muscle is severely damaged and requires the participation from satellite cells in order to repair. Here, we describe a model to study satellite cell behavior in muscle hypertrophy that is independent of muscle regeneration.Synergist ablation surgery involves the surgical removal of the gastrocnemius and soleus muscles resulting in functional overload of the remaining plantaris muscle. This functional overload results in myofiber hypertrophy, as well as the activation, proliferation, and fusion of satellite cells into the myofibers. Within 2 weeks of functional overload, satellite cell content increases approximately 275 %, an increase that is accompanied with a ~60 % increase in the number of myonuclei. Therefore, this can be used as an alternative model to study satellite cell behavior in adulthood that is different from regeneration, and capable of revealing new satellite cell functions in regulating muscle adaptation.

  2. Cholesterol removal from adult skeletal muscle impairs excitation–contraction coupling and aging reduces caveolin-3 and alters the expression of other triadic proteins

    PubMed Central

    Barrientos, Genaro; Llanos, Paola; Hidalgo, Jorge; Bolaños, Pura; Caputo, Carlo; Riquelme, Alexander; Sánchez, Gina; Quest, Andrew F. G.; Hidalgo, Cecilia

    2015-01-01

    Cholesterol and caveolin are integral membrane components that modulate the function/location of many cellular proteins. Skeletal muscle fibers, which have unusually high cholesterol levels in transverse tubules, express the caveolin-3 isoform but its association with transverse tubules remains contentious. Cholesterol removal impairs excitation–contraction (E–C) coupling in amphibian and mammalian fetal skeletal muscle fibers. Here, we show that treating single muscle fibers from adult mice with the cholesterol removing agent methyl-β-cyclodextrin decreased fiber cholesterol by 26%, altered the location pattern of caveolin-3 and of the voltage dependent calcium channel Cav1.1, and suppressed or reduced electrically evoked Ca2+ transients without affecting membrane integrity or causing sarcoplasmic reticulum (SR) calcium depletion. We found that transverse tubules from adult muscle and triad fractions that contain ~10% attached transverse tubules, but not SR membranes, contained caveolin-3 and Cav1.1; both proteins partitioned into detergent-resistant membrane fractions highly enriched in cholesterol. Aging entails significant deterioration of skeletal muscle function. We found that triad fractions from aged rats had similar cholesterol and RyR1 protein levels compared to triads from young rats, but had lower caveolin-3 and glyceraldehyde 3-phosphate dehydrogenase and increased Na+/K+-ATPase protein levels. Both triad fractions had comparable NADPH oxidase (NOX) activity and protein content of NOX2 subunits (p47phox and gp91phox), implying that NOX activity does not increase during aging. These findings show that partial cholesterol removal impairs E–C coupling and alters caveolin-3 and Cav1.1 location pattern, and that aging reduces caveolin-3 protein content and modifies the expression of other triadic proteins. We discuss the possible implications of these findings for skeletal muscle function in young and aged animals. PMID:25914646

  3. Scanning Electron Microscopy Reveals Two Distinct Classes of Erythroblastic Island Isolated from Adult Mammalian Bone Marrow.

    PubMed

    Yeo, Jia Hao; McAllan, Bronwyn M; Fraser, Stuart T

    2016-04-01

    Erythroblastic islands are multicellular clusters in which a central macrophage supports the development and maturation of red blood cell (erythroid) progenitors. These clusters play crucial roles in the pathogenesis observed in animal models of hematological disorders. The precise structure and function of erythroblastic islands is poorly understood. Here, we have combined scanning electron microscopy and immuno-gold labeling of surface proteins to develop a better understanding of the ultrastructure of these multicellular clusters. The erythroid-specific surface antigen Ter-119 and the transferrin receptor CD71 exhibited distinct patterns of protein sorting during erythroid cell maturation as detected by immuno-gold labeling. During electron microscopy analysis we observed two distinct classes of erythroblastic islands. The islands varied in size and morphology, and the number and type of erythroid cells interacting with the central macrophage. Assessment of femoral marrow isolated from a cavid rodent species (guinea pig, Cavis porcellus) and a marsupial carnivore species (fat-tailed dunnarts, Sminthopsis crassicaudata) showed that while the morphology of the central macrophage varied, two different types of erythroblastic islands were consistently identifiable. Our findings suggest that these two classes of erythroblastic islands are conserved in mammalian evolution and may play distinct roles in red blood cell production.

  4. A Novel Model of Traumatic Brain Injury in Adult Zebrafish Demonstrates Response to Injury and Treatment Comparable with Mammalian Models.

    PubMed

    McCutcheon, Victoria; Park, Eugene; Liu, Elaine; Sobhebidari, Pooya; Tavakkoli, Jahan; Wen, Xiao-Yan; Baker, Andrew J

    2016-12-20

    Traumatic brain injury (TBI) is a leading cause of death and morbidity in industrialized countries with considerable associated health care costs. The cost and time associated with pre-clinical development of TBI therapeutics is lengthy and expensive with a poor track record of successful translation to the clinic. The zebrafish is an emerging model organism in research with unique technical and genomic strengths in the study of disease and development. Its high degree of genetic homology and cell signaling pathways relative to mammalian species and amenability to high and medium throughput assays has potential to accelerate the rate of therapeutic drug identification. Accordingly, we developed a novel closed-head model of TBI in adult zebrafish using a targeted, pulsed, high-intensity focused ultrasound (pHIFU) to induce mechanical injury of the brain. Western blot results indicated altered microtubule and neurofilament expression as well as increased expression of cleaved caspase-3 and beta APP (β-APP; p < 0.05). We used automated behavioral tracking software to evaluate locomotor deficits 24 and 48 h post-injury. Significant behavioral impairment included decreased swim distance and velocity (p < 0.05), as well as heightened anxiety and altered group social dynamics. Responses to injury were pHIFU dose-dependent and modifiable with MK-801, MDL-28170, or temperature modulation. Together, results indicate that the zebrafish exhibits responses to injury and intervention similar to mammalian TBI pathophysiology and suggest the potential for use to rapidly evaluate therapeutic compounds with high efficiency.

  5. Synthesis and Characterization of a Model Extracellular Matrix that Induces Partial Regeneration of Adult Mammalian Skin

    NASA Astrophysics Data System (ADS)

    Yannas, I. V.; Lee, E.; Orgill, D. P.; Skrabut, E. M.; Murphy, G. F.

    1989-02-01

    Regeneration of the dermis does not occur spontaneously in the adult mammal. The epidermis is regenerated spontaneously provided there is a dermal substrate over which it can migrate. Certain highly porous, crosslinked collagen--glycosaminoglycan copolymers have induced partial morphogenesis of skin when seeded with dermal and epidermal cells and then grafted on standard, full-thickness skin wounds in the adult guinea pig. A mature epidermis and a nearly physiological dermis, which lacked hair follicles but was demonstrably different from scar, were regenerated over areas as large as 16 cm2. These chemical analogs of extracellular matrices were morphogenetically active provided that the average pore diameter ranged between 20 and 125 μ m, the resistance to degradation by collagenase exceeded a critical limit, and the density of autologous dermal and epidermal cells inoculated therein was >5 × 104 cells per cm2 of wound area. Unseeded copolymers with physical structures that were within these limits delayed the onset of wound contraction by about 10 days but did not eventually prevent it. Seeded copolymers not only delayed contraction but eventually arrested and reversed it while new skin was being regenerated. The data identify a model extracellular matrix that acts as if it were an insoluble growth factor with narrowly specified physicochemical structure, functioning as a transient basal lamina during morphogenesis of skin.

  6. Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin.

    PubMed Central

    Yannas, I V; Lee, E; Orgill, D P; Skrabut, E M; Murphy, G F

    1989-01-01

    Regeneration of the dermis does not occur spontaneously in the adult mammal. The epidermis is regenerated spontaneously provided there is a dermal substrate over which it can migrate. Certain highly porous, crosslinked collagen-glycosaminoglycan copolymers have induced partial morphogenesis of skin when seeded with dermal and epidermal cells and then grafted on standard, full-thickness skin wounds in the adult guinea pig. A mature epidermis and a nearly physiological dermis, which lacked hair follicles but was demonstrably different from scar, were regenerated over areas as large as 16 cm2. These chemical analogs of extracellular matrices were morphogenetically active provided that the average pore diameter ranged between 20 and 125 microns, the resistance to degradation by collagenase exceeded a critical limit, and the density of autologous dermal and epidermal cells inoculated therein was greater than 5 x 10(4) cells per cm2 of wound area. Unseeded copolymers with physical structures that were within these limits delayed the onset of wound contraction by about 10 days but did not eventually prevent it. Seeded copolymers not only delayed contraction but eventually arrested and reversed it while new skin was being regenerated. The data identify a model extracellular matrix that acts as if it were an insoluble growth factor with narrowly specified physiochemical structure, functioning as a transient basal lamina during morphogenesis of skin. Images PMID:2915988

  7. Epigenetic gene regulation in the adult mammalian brain: multiple roles in memory formation.

    PubMed

    Lubin, Farah D

    2011-07-01

    Brain-derived neurotrophic factor (bdnf) is one of numerous gene products necessary for long-term memory formation and dysregulation of bdnf has been implicated in the pathogenesis of cognitive and mental disorders. Recent work indicates that epigenetic-regulatory mechanisms including the markings of histone proteins and associated DNA remain labile throughout the life-span and represent an attractive molecular process contributing to gene regulation in the brain. In this review, important information will be discussed on epigenetics as a set of newly identified dynamic transcriptional mechanisms serving to regulate gene expression changes in the adult brain with particular emphasis on bdnf transcriptional readout in learning and memory formation. This review will also highlight evidence for the role of epigenetics in aberrant bdnf gene regulation in the pathogenesis of cognitive dysfunction associated with seizure disorders, Rett syndrome, Schizophrenia, and Alzheimer's disease. Such research offers novel concepts for understanding epigenetic transcriptional mechanisms subserving adult cognition and mental health, and furthermore promises novel avenues for therapeutic approach in the clinic.

  8. The specific contributions of force and velocity to muscle power in older adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study investigates relative contributions of force and velocity on muscular power and function in middle-aged (MH), older healthy (OH), and older mobility-limited (OML) adults. Seventy-nine men and women underwent tests including leg muscle power at 180deg/sec (SPisok), isometric maximal torq...

  9. Iron Supplementation Effects on Redox Status following Aseptic Skeletal Muscle Trauma in Adults and Children

    PubMed Central

    Tsiokanos, Athanasios; Georgakouli, Kalliopi; Zalavras, Athanasios; Avloniti, Alexandra; Koutedakis, Yiannis

    2017-01-01

    Exercise-induced skeletal muscle microtrauma is characterized by loss of muscle cell integrity, marked aseptic inflammatory response, and oxidative stress. We examined if iron supplementation would alter redox status after eccentric exercise. In a randomized, double blind crossover study, that was conducted in two cycles, healthy adults (n = 14) and children (n = 11) received daily either 37 mg of elemental iron or placebo for 3 weeks prior to and up to 72 h after an acute eccentric exercise bout. Blood was drawn at baseline, before exercise, and 72 h after exercise for the assessment of iron status, creatine kinase activity (CK), and redox status. Iron supplementation at rest increased iron concentration and transferrin saturation (p < 0.01). In adults, CK activity increased at 72 h after exercise, while no changes occurred in children. Iron supplementation increased TBARS at 72 h after exercise in both adults and children; no changes occurred under placebo condition. Eccentric exercise decreased bilirubin concentration at 72 h in all groups. Iron supplementation can alter redox responses after muscle-damaging exercise in both adults and children. This could be of great importance not only for healthy exercising individuals, but also in clinical conditions which are characterized by skeletal muscle injury and inflammation, yet iron supplementation is crucial for maintaining iron homeostasis. This study was registered at Clinicaltrials.gov Identifier: NCT02374619. PMID:28203319

  10. Skeletal muscle TLR4 and TACE are associated with body fat percentage in older adults.

    PubMed

    Timmerman, Kyle L; Connors, Ian D; Deal, Michael A; Mott, Rachael E

    2016-04-01

    Elevated skeletal muscle expression of toll-like receptor 4 (TLR4) has been linked to increased inflammation in clinical populations. TNFα converting enzyme (TACE), which cleaves membrane-bound TNFα (mTNFα) to its soluble (sTNFα) and more bioactive form, has been linked to chronic disease. In contrast, higher physical activity level is associated with decreased chronic disease risk and inflammation. The purpose of the present study was to examine the relationship between physical activity and skeletal muscle TLR4, TACE, and TNFα in older adults. In 26 older adults (age = 68 ± 4 years, body mass index = 26 ± 3 kg·m(-2)), self-reported physical activity (kcal·week(-1)), estimated maximal oxygen consumption, and body composition (air plethysmography) were measured. TLR4, TACE, mTNFα, and sTNFα were measured in skeletal muscle biopsies (vastus lateralis) using western blot analyses. Pearson product-moment correlations were run between variables. Significance was set at p < 0.05. Skeletal muscle TACE was directly associated with sTNFα (r = 0.53, p < 0.01). Linear regression modeling showed that mTNFα and TACE expression were predictive of sTNFα expression. No correlations were observed between physical activity and TLR4, TACE, or sTNFα. Percent body fat was directly associated with skeletal muscle TLR4 (r = 0.52, p < 0.01) and TACE (r = 0.50, p < 0.01), whereas fasting blood glucose was directly associated with TACE and sTNFα. In conclusion, we found that percent body fat was directly associated with TLR4 and TACE expression in skeletal muscle of older adults. These findings suggest that elevated skeletal muscle expression of TLR4 and TACE may contribute to the augmented inflammation and chronic disease risk observed with increased adiposity.

  11. Effect of seven days of spaceflight on hindlimb muscle protein, RNA and DNA in adult rats

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1985-01-01

    Effects of seven days of spaceflight on skeletal muscle (soleus, gastrocnemius, EDL) content of protein, RNA and DNA were determined in adult rats. Whereas total protein contents were reduced in parallel with muscle weights, myofibrillar protein appeared to be more affected. There were no significant changes in absolute DNA contents, but a significant (P less than 0.05) increase in DNA concentration (microgram/milligram) in soleus muscles from flight rats. Absolute RNA contents were significantly (P less than 0.025) decreased in the soleus and gastrocnemius muscles of flight rats, with RNA concentrations reduced 15-30 percent. These results agree with previous ground-based observations on the suspended rat with unloaded hindlimbs and support continued use of this model.

  12. Longitudinal decline of lower extremity muscle power in healthy and mobility-limited older adults: influence of muscle mass, strength, composition, neuromuscular activation and single fiber contractile properties

    PubMed Central

    Reid, Kieran F.; Pasha, Evan; Doros, Gheorghe; Clark, David J.; Patten, Carolynn; Phillips, Edward M.; Frontera, Walter R.; Fielding, Roger A.

    2013-01-01

    Purpose This longitudinal study examined the major physiological mechanisms that determine the age-related loss of lower extremity muscle power in two distinct groups of older humans. We hypothesized that after ~ 3 years of follow-up, mobility-limited older adults (mean age: 77.2 ± 4, n = 22, 12 females) would have significantly greater reductions in leg extensor muscle power compared to healthy older adults (74.1 ± 4, n = 26, 12 females). Methods Mid-thigh muscle size and composition were assessed using computed tomography. Neuromuscular activation was quantified using surface electromyography and vastus lateralis single muscle fibers were studied to evaluate intrinsic muscle contractile properties. Results At follow-up, the overall magnitude of muscle power loss was similar between groups: mobility-limited: −8.5% vs. healthy older: −8.8%, P > 0.8. Mobility-limited elders had significant reductions in muscle size (−3.8%, P< 0.01) and strength (−5.9%, P< 0.02), however, these parameters were preserved in healthy older (P ≥ 0.7). Neuromuscular activation declined significantly within healthy older but not in mobility-limited participants. Within both groups, the cross sectional areas of type I and type IIA muscle fibers were preserved while substantial increases in single fiber peak force ( > 30%), peak power (> 200%) and unloaded shortening velocity (>50%) were elicited at follow-up. Conclusion Different physiological mechanisms contribute to the loss of lower extremity muscle power in healthy older and mobility-limited older adults. Neuromuscular changes may be the critical early determinant of muscle power deficits with aging. In response to major whole muscle decrements, major compensatory mechanisms occur within the contractile properties of surviving single muscle fibers in an attempt to restore overall muscle power and function with advancing age. PMID:24122149

  13. Response of the JAK-STAT pathway to mammalian hibernation in 13-lined ground squirrel striated muscle.

    PubMed

    Logan, Samantha M; Tessier, Shannon N; Tye, Joann; Storey, Kenneth B

    2016-03-01

    Over the course of the torpor-arousal cycle, hibernators must make behavioral, physiological, and molecular rearrangements in order to keep a very low metabolic rate and retain organ viability. 13-lined ground squirrels (Ictidomys tridecemlineatus) remain immobile during hibernation, and although the mechanisms of skeletal muscle survival are largely unknown, studies have shown minimal muscle loss in hibernating organisms. Additionally, the ground squirrel heart undergoes cold-stress, reversible cardiac hypertrophy, and ischemia-reperfusion without experiencing fatal impairment. This study examines the role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway in the regulation of cell stress in cardiac and skeletal muscles, comparing euthermic and hibernating ground squirrels. Immunoblots showed a fivefold decrease in JAK3 expression during torpor in skeletal muscle, along with increases in STAT3 and 5 phosphorylation and suppressors of cytokine signaling-1 (SOCS1) protein levels. Immunoblots also showed coordinated increases in STAT1, 3 and 5 phosphorylation and STAT1 inhibitor protein expression in cardiac muscle during torpor. PCR analysis revealed that the activation of these pro-survival signaling cascades did not result in coordinate changes in downstream genes such as anti-apoptotic B-cell lymphoma-2 (Bcl-2) family gene expression. Overall, these results indicate activation of the JAK-STAT pathway in both cardiac and skeletal muscles, suggesting a response to cellular stress during hibernation.

  14. Increased Muscle Stress-Sensitivity Induced by Selenoprotein N Inactivation in Mouse: A Mammalian Model for SEPN1-Related Myopathy

    PubMed Central

    Arbogast, Sandrine; Lainé, Jeanne; Vassilopoulos, Stéphane; Beuvin, Maud; Dubourg, Odile; Vignaud, Alban; Ferry, Arnaud; Krol, Alain; Allamand, Valérie; Guicheney, Pascale; Ferreiro, Ana; Lescure, Alain

    2011-01-01

    Selenium is an essential trace element and selenoprotein N (SelN) was the first selenium-containing protein shown to be directly involved in human inherited diseases. Mutations in the SEPN1 gene, encoding SelN, cause a group of muscular disorders characterized by predominant affection of axial muscles. SelN has been shown to participate in calcium and redox homeostasis, but its pathophysiological role in skeletal muscle remains largely unknown. To address SelN function in vivo, we generated a Sepn1-null mouse model by gene targeting. The Sepn1−/− mice had normal growth and lifespan, and were macroscopically indistinguishable from wild-type littermates. Only minor defects were observed in muscle morphology and contractile properties in SelN-deficient mice in basal conditions. However, when subjected to challenging physical exercise and stress conditions (forced swimming test), Sepn1−/− mice developed an obvious phenotype, characterized by limited motility and body rigidity during the swimming session, as well as a progressive curvature of the spine and predominant alteration of paravertebral muscles. This induced phenotype recapitulates the distribution of muscle involvement in patients with SEPN1-Related Myopathy, hence positioning this new animal model as a valuable tool to dissect the role of SelN in muscle function and to characterize the pathophysiological process. PMID:21858002

  15. Effect of mesenchymal stem cells on induced skeletal muscle chemodenervation atrophy in adult male albino rats.

    PubMed

    Shehata, Azza S; Al-Ghonemy, Nabila M; Ahmed, Samah M; Mohamed, Samar R

    2017-04-01

    The present research was conducted to evaluate the effect of bone marrow derived mesenchymal stem cells (BM-MSCs) as a potential therapeutic tool for improvement of skeletal muscle recovery after induced chemodenervation atrophy by repeated local injection of botulinum toxin-A in the right tibialis anterior muscle of adult male albino rats. Forty five adult Wistar male albino rats were classified into control and experimental groups. Experimental group was further subdivided into 3 equal subgroups; induced atrophy, BM-MSCs treated and recovery groups. Biochemical analysis of serum LDH, CK and Real-time PCR for Bcl-2, caspase 3 and caspase 9 was measured. Skeletal muscle sections were stained with H and E, Mallory trichrome, and Immunohistochemical reaction for Bax and CD34. Improvement in the skeletal muscle histological structure was noticed in BM-MSCs treated group, however, in the recovery group, some sections showed apparent transverse striations and others still affected. Immunohistochemical reaction of Bax protein showed strong positive immunoreaction in the cytoplasm of muscle fibers in the induced atrophy group. BM-MSCs treated group showed weak positive reaction while the recovery group showed moderate reaction in the cytoplasm of muscle fibers. Immunohistochemical reaction for CD34 revealed occasional positive CD34 stained cells in the induced atrophy group. In BM-MSCs treated group, multiple positive CD34 stained cells were detected. However, recovery group showed some positive CD34 stained cells at the periphery of the muscle fibers. Marked improvement in the regenerative capacity of skeletal muscles after BM-MSCs therapy. Hence, stem cell therapy provides a new hope for patients suffering from myopathies and severe injuries.

  16. Older adults use a unique strategy to lift inertial loads with the elbow flexor muscles.

    PubMed

    Graves, A E; Kornatz, K W; Enoka, R M

    2000-04-01

    The purpose of this study was to determine the effect of age on the ability to exert steady forces and to perform steady flexion movements with the muscles that cross the elbow joint. An isometric task required subjects to exert a steady force to match a target force that was displayed on a monitor. An anisometric task required subjects to raise and lower inertial loads so that the angular displacement around the elbow joint matched a template displayed on a monitor. Steadiness was measured as the coefficient of variation of force and as the normalized standard deviation of wrist acceleration. For the isometric task, steadiness as a function of target force decreased similarly for old adults and young adults. For the anisometric task, steadiness increased as a function of the inertial load and there were significant differences caused by age. Old adults were less steady than young adults during both shortening and lengthening contractions with the lightest loads. Furthermore, old adults were least steady when performing lengthening contractions. These behaviors appear to be associated with the patterns of muscle activation. These results suggest that different neural strategies are used to control isometric and anisometric contractions performed with the elbow flexor muscles and that these strategies do not change in parallel with advancing age.

  17. Normal and Malignant Muscle Cell Transplantation into Immune Compromised Adult Zebrafish

    PubMed Central

    Moore, John C.; Langenau, David M.

    2014-01-01

    Zebrafish have become a powerful tool for assessing development, regeneration, and cancer. More recently, allograft cell transplantation protocols have been developed that permit engraftment of normal and malignant cells into irradiated, syngeneic, and immune compromised adult zebrafish. These models when coupled with optimized cell transplantation protocols allow for the rapid assessment of stem cell function, regeneration following injury, and cancer. Here, we present a method for cell transplantation of zebrafish adult skeletal muscle and embryonal rhabdomyosarcoma (ERMS), a pediatric sarcoma that shares features with embryonic muscle, into immune compromised adult rag2E450fs homozygous mutant zebrafish. Importantly, these animals lack T cells and have reduced B cell function, facilitating engraftment of a wide range of tissues from unrelated donor animals. Our optimized protocols show that fluorescently labeled muscle cell preparations from α-actin-RFP transgenic zebrafish engraft robustly when implanted into the dorsal musculature of rag2 homozygous mutant fish. We also demonstrate engraftment of fluorescent-transgenic ERMS where fluorescence is confined to cells based on differentiation status. Specifically, ERMS were created in AB-strain myf5-GFP; mylpfa-mCherry double transgenic animals and tumors injected into the peritoneum of adult immune compromised fish. The utility of these protocols extends to engraftment of a wide range of normal and malignant donor cells that can be implanted into dorsal musculature or peritoneum of adult zebrafish. PMID:25591079

  18. Detection, Characterization, and Spontaneous Differentiation In Vitro of Very Small Embryonic-Like Putative Stem Cells in Adult Mammalian Ovary

    PubMed Central

    Parte, Seema; Telang, Jyoti; Daithankar, Vinita; Salvi, Vinita; Zaveri, Kusum; Hinduja, Indira

    2011-01-01

    The present study was undertaken to detect, characterize, and study differentiation potential of stem cells in adult rabbit, sheep, monkey, and menopausal human ovarian surface epithelium (OSE). Two distinct populations of putative stem cells (PSCs) of variable size were detected in scraped OSE, one being smaller and other similar in size to the surrounding red blood cells in the scraped OSE. The smaller 1–3 μm very small embryonic-like PSCs were pluripotent in nature with nuclear Oct-4 and cell surface SSEA-4, whereas the bigger 4–7 μm cells with cytoplasmic localization of Oct-4 and minimal expression of SSEA-4 were possibly the tissue committed progenitor stem cells. Pluripotent gene transcripts of Oct-4, Oct-4A, Nanog, Sox-2, TERT, and Stat-3 in human and sheep OSE were detected by reverse transcriptase–polymerase chain reaction. The PSCs underwent spontaneous differentiation into oocyte-like structures, parthenote-like structures, embryoid body-like structures, cells with neuronal-like phenotype, and embryonic stem cell-like colonies, whereas the epithelial cells transformed into mesenchymal phenotype by epithelial–mesenchymal transition in 3 weeks of OSE culture. Germ cell markers like c-Kit, DAZL, GDF-9, VASA, and ZP4 were immuno-localized in oocyte-like structures. In conclusion, as opposed to the existing view of OSE being a bipotent source of oocytes and granulosa cells, mammalian ovaries harbor distinct very small embryonic-like PSCs and tissue committed progenitor stem cells population that have the potential to develop into oocyte-like structures in vitro, whereas mesenchymal fibroblasts appear to form supporting granulosa-like somatic cells. Research at the single-cell level, including complete gene expression profiling, is required to further confirm whether postnatal oogenesis is a conserved phenomenon in adult mammals. PMID:21291304

  19. Detection, characterization, and spontaneous differentiation in vitro of very small embryonic-like putative stem cells in adult mammalian ovary.

    PubMed

    Parte, Seema; Bhartiya, Deepa; Telang, Jyoti; Daithankar, Vinita; Salvi, Vinita; Zaveri, Kusum; Hinduja, Indira

    2011-08-01

    The present study was undertaken to detect, characterize, and study differentiation potential of stem cells in adult rabbit, sheep, monkey, and menopausal human ovarian surface epithelium (OSE). Two distinct populations of putative stem cells (PSCs) of variable size were detected in scraped OSE, one being smaller and other similar in size to the surrounding red blood cells in the scraped OSE. The smaller 1-3 μm very small embryonic-like PSCs were pluripotent in nature with nuclear Oct-4 and cell surface SSEA-4, whereas the bigger 4-7 μm cells with cytoplasmic localization of Oct-4 and minimal expression of SSEA-4 were possibly the tissue committed progenitor stem cells. Pluripotent gene transcripts of Oct-4, Oct-4A, Nanog, Sox-2, TERT, and Stat-3 in human and sheep OSE were detected by reverse transcriptase-polymerase chain reaction. The PSCs underwent spontaneous differentiation into oocyte-like structures, parthenote-like structures, embryoid body-like structures, cells with neuronal-like phenotype, and embryonic stem cell-like colonies, whereas the epithelial cells transformed into mesenchymal phenotype by epithelial-mesenchymal transition in 3 weeks of OSE culture. Germ cell markers like c-Kit, DAZL, GDF-9, VASA, and ZP4 were immuno-localized in oocyte-like structures. In conclusion, as opposed to the existing view of OSE being a bipotent source of oocytes and granulosa cells, mammalian ovaries harbor distinct very small embryonic-like PSCs and tissue committed progenitor stem cells population that have the potential to develop into oocyte-like structures in vitro, whereas mesenchymal fibroblasts appear to form supporting granulosa-like somatic cells. Research at the single-cell level, including complete gene expression profiling, is required to further confirm whether postnatal oogenesis is a conserved phenomenon in adult mammals.

  20. Metabolic profile of the perivertebral muscles in small therian mammals: implications for the evolution of the mammalian trunk musculature.

    PubMed

    Schilling, Nadja

    2009-01-01

    In order to gain a better understanding of the ancestral properties of the perivertebral muscles of mammals, this study investigated the fiber type composition of these muscles in six small, extant therians (two metatherians and four eutherians) similar in body shape to early mammals. Despite a few species-specific differences, the investigated species were very similar in their overall distribution of fiber types indicating similar functional demands on the back muscles in mammals of this body size and shape. Deep and short, mono- or multisegmental muscles (i.e., mm. interspinales, intermammillares, rotatores et intertransversarii) consistently showed the highest percentage of slow, oxidative fibers implying a function as local stabilizers of the vertebral column. Superficial and large, polysegmental muscles (i.e., mm. multifidus, sacrospinalis, iliopsoas et psoas minor) were predominantly composed of fast, glycolytic fibers suggesting they function to both globally stabilize and mobilize the spine during rapid non-locomotor and locomotor activities. Some muscles contained striking accumulations of oxidative fibers in specific regions (mm. longissimus et quadratus lumborum). These regions are hypothesized to function independently from the rest of the muscle belly and may be comparable in their functionality to regionalized limb muscles. The deep, central oxidative region in the m. longissimus lumborum appears to be a general feature of mammals and likely serves a proprioceptive function to control the postural equilibrium of the pelvic girdle and lumbar spine. The potential functions of the m. quadratus lumborum during ventilation and ventral stabilization of the vertebral column are discussed. Because representatives of the stem lineage of mammals were comparable in their body proportions and probably also locomotor parameters to the species investigated here, I suggest that the described fiber type distribution is representative of the ancestral condition in

  1. Fm1-43 reveals membrane recycling in adult inner hair cells of the mammalian cochlea.

    PubMed

    Griesinger, Claudius B; Richards, Chistopher D; Ashmore, Jonathan F

    2002-05-15

    Neural transmission of complex sounds demands fast and sustained rates of synaptic release from the primary cochlear receptors, the inner hair cells (IHCs). The cells therefore require efficient membrane recycling. Using two-photon imaging of the membrane marker FM1-43 in the intact sensory epithelium within the cochlear bone of the adult guinea pig, we show that IHCs possess fast calcium-dependent membrane uptake at their apical pole. FM1-43 did not permeate through the stereocilial mechanotransducer channel because uptake kinetics were neither changed by the blockers dihydrostreptomycin and d-tubocurarine nor by treatment of the apical membrane with BAPTA, known to disrupt mechanotransduction. Moreover, the fluid phase marker Lucifer Yellow produced a similar labeling pattern to FM1-43, consistent with FM1-43 uptake via endocytosis. We estimate the membrane retrieval rate at approximately 0.5% of the surface area of the cell per second. Labeled membrane was rapidly transported to the base of IHCs by kinesin-dependent trafficking and accumulated in structures that resembled synaptic release sites. Using confocal imaging of FM1-43 in excised strips of the organ of Corti, we show that the time constants of fluorescence decay at the basolateral pole of IHCs and apical endocytosis were increased after depolarization of IHCs with 40 mm potassium, a stimulus that triggers calcium influx and increases synaptic release. Blocking calcium channels with either cadmium or nimodipine during depolarization abolished the rate increase of apical endocytosis. We suggest that IHCs use fast calcium-dependent apical endocytosis for activity-associated replenishment of synaptic membrane.

  2. Increased rat neonatal activity influences adult cytokine levels and relative muscle mass

    PubMed Central

    Buchowicz, Bryce; Yu, Tiffany; Nance, Dwight M.; Zaldivar, Frank P.; Cooper, Dan M.; Adams, Gregory R.

    2011-01-01

    Little is known about the effect of physical activity in early life on subsequent growth and regulation of inflammation. We previously reported that exposure of muscles in growing rats to IL-6 results in decreased muscle growth apparently due to a state of resistance to growth factors such IGF-I and that running exercise could ameliorate this growth defect. Herein we hypothesized that increased activity, for a brief period during neonatal life, would pattern the adult rat towards a less inflammatory phenotype. Neonatal rats were induced to move about their cage for brief periods from day 5 to day 15 postpartum. Additional groups were undisturbed controls (CON) and handled (HAND). Sub-groups of rats were sampled at 30 and 65 days of age. Relative to CON and HAND, neonatal exercise (EX) results in decreased circulating levels of TNFα, IL-6 and IL-1β in adulthood, primarily in male rats. In addition, adult male EX rats had lower body mass and increased skeletal muscle mass suggesting a leaner phenotype. The results of this study suggest that moderate increases in activity early in life can influence the adult toward a more healthy phenotype with regard to inflammatory mediators and relative muscle mass. PMID:20657345

  3. Effects of increasing physical activity on foot structure and ankle muscle strength in adults with obesity

    PubMed Central

    Zhao, Xiaoguang; Tsujimoto, Takehiko; Kim, Bokun; Katayama, Yasutomi; Wakaba, Kyousuke; Wang, Zhennan; Tanaka, Kiyoji

    2016-01-01

    [Purpose] The purpose of this study was to examine the effects of increasing physical activity on foot structure and ankle muscle strength in adults with obesity and to verify whether the rate of change in foot structure is related to that in ankle muscle strength. [Subjects and Methods] Twenty-seven adults with obesity completed a 12-week program in which the intensity of physical activity performed was gradually increased. Physical activity was monitored using a three-axis accelerometer. Foot structure was assessed using a three-dimensional foot scanner, while ankle muscle strength was measured using a dynamometry. [Results] With the increasing physical activity, the participants’ feet became thinner (the rearfoot width, instep height, and girth decreased) and the arch became higher (the arch height index increased) and stiffer (the arch stiffness index increased); the ankle muscle strength also increased after the intervention. Additionally, the changes in the arch height index and arch stiffness index were not associated with changes in ankle muscle strength. [Conclusion] Increasing physical activity may be one possible approach to improve foot structure and function in individuals with obesity. PMID:27630426

  4. Abdominal muscle and epipubic bone function during locomotion in Australian possums: insights to basal mammalian conditions and Eutherian-like tendencies in Trichosurus.

    PubMed

    Reilly, Stephen M; McElroy, Eric J; White, Thomas D; Biknevicius, Audrone R; Bennett, Michael B

    2010-04-01

    Mammals have four hypaxial muscle layers that wrap around the abdomen between the pelvis, ribcage, and spine. However, the marsupials have epipubic bones extending anteriorly into the ventral hypaxial layers with two additional muscles extending to the ventral midline and femur. Comparisons of South American marsupials to basal eutherians have shown that all of the abdominal hypaxials are active bilaterally in resting ventilation. However, during locomotion marsupials employ an asymmetrical pattern of activity as the hypaxial muscles form a crosscouplet linkage that uses the epipubic bone as a lever to provide long-axis support of the body between diagonal limb couplets during each step. In basal eutherians, this system shifts off the femur and epipubic bones (which are lost) resulting in a shoulder to pelvis linkage associated with shifts in both the positions and activity patterns of the pectineus and rectus abdominis muscles during locomotion. In this study, we present data on hypaxial function in two species (Pseudocheirus peregrinus and Trichosurus vulpecula) representing the two major radiations of possums in Australia: the Pseudocheiridae (within the Petauroidea) and the Phalangeridae. Patterns of gait, motor activity, and morphology in these two Australian species were compared with previous work to examine the generality of 1) the crosscouplet lever system as the basal condition for the Marsupialia and 2) several traits hypothesized to be common to all mammals (hypaxial tonus during resting ventilation, ventilation to step synchrony during locomotion, and bilateral transversus abdominis activity during locomotor expiration). Our results validate the presence of the crosscouplet pattern and basic epipubic bone lever system in Australian possums and confirm the generality of basal mammalian patterns. However, several novelties discovered in Trichosurus, reveal that it exhibits an evolutionary transition to intermediate eutherian-like morphological and motor

  5. Sarcopenia and physical independence in older adults: the independent and synergic role of muscle mass and muscle function

    PubMed Central

    dos Santos, Leandro; Cyrino, Edilson S.; Antunes, Melissa; Santos, Diana A.

    2016-01-01

    Abstract Background The loss of skeletal muscle mass (MM) or muscle function (MF) alone increases the risk for losing physical independence in older adults. We aimed to examine the independent and synergic associations of low MM and low MF, both criteria of sarcopenia, with the risk for losing projected physical independence in later life (+90 years old). Methods Cross‐sectional analyses were conducted in 3493 non‐institutionalized older adults (1166 males). Physical independence was assessed with a 12‐item composite physical function scale. Logistic regression was used to estimate the odds‐ratio (OR) for being at risk for losing physical independence. Results Approximately 30% of the participants were at risk for losing physical independence at 90 years of age. Independent analysis demonstrated that participants with low MM had 1.65 (95%CI: 1.27–2.31) increased odds for being at risk for losing physical independence and participants with low MF had 6.19 (95%CI 5.08–7.53) increased odds for being at risk. Jointly, having a low MM and a low MF increased the risk for losing physical independence to 12.28 (95%CI 7.95 to 18.96). Conclusions Although low MM represents a risk factor for losing physical independence, low MF seems to play a more dominant role in this relationship, with the presence of both sarcopenia criteria representing a substantial risk for losing physical independence in later life. PMID:27897417

  6. IP3-dependent, post-tetanic calcium transients induced by electrostimulation of adult skeletal muscle fibers

    PubMed Central

    Casas, Mariana; Figueroa, Reinaldo; Jorquera, Gonzalo; Escobar, Matías; Molgó, Jordi

    2010-01-01

    Tetanic electrical stimulation induces two separate calcium signals in rat skeletal myotubes, a fast one, dependent on Cav 1.1 or dihydropyridine receptors (DHPRs) and ryanodine receptors and related to contraction, and a slow signal, dependent on DHPR and inositol trisphosphate receptors (IP3Rs) and related to transcriptional events. We searched for slow calcium signals in adult muscle fibers using isolated adult flexor digitorum brevis fibers from 5–7-wk-old mice, loaded with fluo-3. When stimulated with trains of 0.3-ms pulses at various frequencies, cells responded with a fast calcium signal associated with muscle contraction, followed by a slower signal similar to one previously described in cultured myotubes. Nifedipine inhibited the slow signal more effectively than the fast one, suggesting a role for DHPR in its onset. The IP3R inhibitors Xestospongin B or C (5 µM) also inhibited it. The amplitude of post-tetanic calcium transients depends on both tetanus frequency and duration, having a maximum at 10–20 Hz. At this stimulation frequency, an increase of the slow isoform of troponin I mRNA was detected, while the fast isoform of this gene was inhibited. All three IP3R isoforms were present in adult muscle. IP3R-1 was differentially expressed in different types of muscle fibers, being higher in a subset of fast-type fibers. Interestingly, isolated fibers from the slow soleus muscle did not reveal the slow calcium signal induced by electrical stimulus. These results support the idea that IP3R-dependent slow calcium signals may be characteristic of distinct types of muscle fibers and may participate in the activation of specific transcriptional programs of slow and fast phenotype. PMID:20837675

  7. Leg and trunk muscle coordination and postural sway during increasingly difficult standing balance tasks in young and older adults.

    PubMed

    Donath, Lars; Kurz, Eduard; Roth, Ralf; Zahner, Lukas; Faude, Oliver

    2016-09-01

    Ageing impairs body balance and increases older adults' fall risk. Balance training can improve intrinsic fall risk factors. However, age comparisons of muscle activity responses during balance tasks are lacking. This study investigated relative muscle activity, muscle coordination and postural sway during various recommended static balance training tasks. Muscle activity (%MVC), amplitude ratios (AR) and co-activity (CAI) were determined during standing tasks for 30s (1: double limb stance on a foam surface, eyes open; 2: double limb stance on firm ground, eyes closed; 3: double limb stance, feet in step position on a foam surface, eyes open; 4: double limb stance, feet in step position on firm ground, eyes closed; 5: single limb stance on firm ground, eyes open) in 20 healthy young adults (24±2 y) and 20 older adults (73±6 y). Surface electromyography (SEMG) was applied (SENIAM guidelines) to ankle (tibialis anterior, soleus, medial gastrocnemius, peroneus longus) and thigh (vastus lateralis, vastus medialis, biceps femoris, semitendinosus) muscles (non-dominant leg). Electrodes over trunk (multifidus and internal oblique) muscles were applied bilaterally. Two- to six-fold higher levels of relative muscle activity were found in older adults for ankle (0.0002muscles. Co-activation was elevated in young adults for the trunk (0.001adults for the ankle (0.009muscle coordination patterns during all stance conditions at the ankle (0.06<ηp(2)<0.28) and the trunk (0.14<ηp(2)<0.23). Older adults had higher electrophysiological costs for all stance conditions. Muscle coordination showed inverse activity patterns at the ankle and trunk. Optimal balance and strength training programs should take into account age-specific alterations in muscle activity.

  8. Mature adult dystrophic mouse muscle environment does not impede efficient engrafted satellite cell regeneration and self-renewal.

    PubMed

    Boldrin, Luisa; Zammit, Peter Steven; Muntoni, Francesco; Morgan, Jennifer Elizabeth

    2009-10-01

    Changes that occur in the skeletal muscle environment with the progress of muscular dystrophies may affect stem cell function and result in impaired muscle regeneration. It has previously been suggested that the success of stem cell transplantation could therefore be dependent both on the properties of the cell itself and on the host muscle environment. Here we engrafted young and mature adult mdx-nude mice, which are the genetic homolog of Duchenne muscular dystrophy, with a small number of satellite cells freshly isolated from young, normal donor mice. We found that the donor satellite cells contributed to muscle regeneration and self-renewal as efficiently within mature adult, as in young, dystrophic host muscle. Donor-derived satellite cells also contributed to robust regeneration after further injury, showing that they were functional despite the more advanced dystrophic muscle environment. These findings provide evidence that muscle tissue in a later stage of dystrophy may be effectively treated by stem cells.

  9. Cav1.1 controls frequency-dependent events regulating adult skeletal muscle plasticity.

    PubMed

    Jorquera, Gonzalo; Altamirano, Francisco; Contreras-Ferrat, Ariel; Almarza, Gonzalo; Buvinic, Sonja; Jacquemond, Vincent; Jaimovich, Enrique; Casas, Mariana

    2013-03-01

    An important pending question in neuromuscular biology is how skeletal muscle cells decipher the stimulation pattern coming from motoneurons to define their phenotype as slow or fast twitch muscle fibers. We have previously shown that voltage-gated L-type calcium channel (Cav1.1) acts as a voltage sensor for activation of inositol (1,4,5)-trisphosphate [Ins(1,4,5)P₃]-dependent Ca(2+) signals that regulates gene expression. ATP released by muscle cells after electrical stimulation through pannexin-1 channels plays a key role in this process. We show now that stimulation frequency determines both ATP release and Ins(1,4,5)P₃ production in adult skeletal muscle and that Cav1.1 and pannexin-1 colocalize in the transverse tubules. Both ATP release and increased Ins(1,4,5)P₃ was seen in flexor digitorum brevis fibers stimulated with 270 pulses at 20 Hz, but not at 90 Hz. 20 Hz stimulation induced transcriptional changes related to fast-to-slow muscle fiber phenotype transition that required ATP release. Addition of 30 µM ATP to fibers induced the same transcriptional changes observed after 20 Hz stimulation. Myotubes lacking the Cav1.1-α1 subunit released almost no ATP after electrical stimulation, showing that Cav1.1 has a central role in this process. In adult muscle fibers, ATP release and the transcriptional changes produced by 20 Hz stimulation were blocked by both the Cav1.1 antagonist nifedipine (25 µM) and by the Cav1.1 agonist (-)S-BayK 8644 (10 µM). We propose a new role for Cav1.1, independent of its calcium channel activity, in the activation of signaling pathways allowing muscle fibers to decipher the frequency of electrical stimulation and to activate specific transcriptional programs that define their phenotype.

  10. Nebulin deficiency in adult muscle causes sarcomere defects and muscle-type-dependent changes in trophicity: novel insights in nemaline myopathy.

    PubMed

    Li, Frank; Buck, Danielle; De Winter, Josine; Kolb, Justin; Meng, Hui; Birch, Camille; Slater, Rebecca; Escobar, Yael Natelie; Smith, John E; Yang, Lin; Konhilas, John; Lawlor, Michael W; Ottenheijm, Coen; Granzier, Henk L

    2015-09-15

    Nebulin is a giant filamentous protein that is coextensive with the actin filaments of the skeletal muscle sarcomere. Nebulin mutations are the main cause of nemaline myopathy (NEM), with typical adult patients having low expression of nebulin, yet the roles of nebulin in adult muscle remain poorly understood. To establish nebulin's functional roles in adult muscle, we studied a novel conditional nebulin KO (Neb cKO) mouse model in which nebulin deletion was driven by the muscle creatine kinase (MCK) promotor. Neb cKO mice are born with high nebulin levels in their skeletal muscles, but within weeks after birth nebulin expression rapidly falls to barely detectable levels Surprisingly, a large fraction of the mice survive to adulthood with low nebulin levels (<5% of control), contain nemaline rods and undergo fiber-type switching toward oxidative types. Nebulin deficiency causes a large deficit in specific force, and mechanistic studies provide evidence that a reduced fraction of force-generating cross-bridges and shortened thin filaments contribute to the force deficit. Muscles rich in glycolytic fibers upregulate proteolysis pathways (MuRF-1, Fbxo30/MUSA1, Gadd45a) and undergo hypotrophy with smaller cross-sectional areas (CSAs), worsening their force deficit. Muscles rich in oxidative fibers do not have smaller weights and can even have hypertrophy, offsetting their specific-force deficit. These studies reveal nebulin as critically important for force development and trophicity in adult muscle. The Neb cKO phenocopies important aspects of NEM (muscle weakness, oxidative fiber-type predominance, variable trophicity effects, nemaline rods) and will be highly useful to test therapeutic approaches to ameliorate muscle weakness.

  11. Functional redundancy and nonredundancy between two Troponin C isoforms in Drosophila adult muscles.

    PubMed

    Chechenova, Maria B; Maes, Sara; Oas, Sandy T; Nelson, Cloyce; Kiani, Kaveh G; Bryantsev, Anton L; Cripps, Richard M

    2017-03-15

    We investigated the functional overlap of two muscle Troponin C (TpnC) genes that are expressed in the adult fruit fly, Drosophila melanogaster: TpnC4 is predominantly expressed in the indirect flight muscles (IFMs), whereas TpnC41C is the main isoform in the tergal depressor of the trochanter muscle (TDT; jump muscle). Using CRISPR/Cas9, we created a transgenic line with a homozygous deletion of TpnC41C and compared its phenotype to a line lacking functional TpnC4 We found that the removal of either of these genes leads to expression of the other isoform in both muscle types. The switching between isoforms occurs at the transcriptional level and involves minimal enhancers located upstream of the transcription start points of each gene. Functionally, the two TpnC isoforms were not equal. Although ectopic TpnC4 in TDT muscles was able to maintain jumping ability, TpnC41C in IFMs could not effectively support flying. Simultaneous functional disruption of both TpnC genes resulted in jump-defective and flightless phenotypes of the survivors, as well as abnormal sarcomere organization. These results indicated that TpnC is required for myofibril assembly, and that there is functional specialization among TpnC isoforms in Drosophila.

  12. Effects of bridge exercises with a sling and vibrations on abdominal muscle thickness in healthy adults.

    PubMed

    Gong, Won-tae

    2015-01-01

    In the present study, we aimed to examine the changes in the thickness of the transversus abdominis (TrA) and internal oblique (Io) muscles using ultrasonography in adults who performed bridge exercises with the abdominal drawing-in maneuver and a sling and received micro vibrations. In total, 32 subjects were divided into a therapy (n= 16) and control (n= 16) groups. The therapy group completed nine sets, with four repetitions, of bridge exercises with the sling and received vibrations. The control group completed nine sets, with four repetitions, of bridge exercises with the sling and did not receive vibrations. The thicknesses of the TrA and Io muscles were measured in both groups using ultrasonography before and after therapy. According to the pressure applied to the biofeedback unit, both groups showed significant changes in the thicknesses of the TrA and Io muscles after therapy (P< 0.05). The change in the thickness of the TrA muscle after therapy was significantly different between the 2 groups when the pressures applied at 38, 42, and 46 mmHg (P< 0.05). Moreover, the change in the thickness of the Io muscle did not significantly different between the 2 groups at any of the pressures applied (P> 0.05). These findings indicate that approximately 15 minutes of vibrations during bridge exercises on unstable surfaces with a sling facilitates the activation of the deep trunk muscles and further enhances the activation of the TrA.

  13. An analysis of the temperature dependence of force, during steady shortening at different velocities, in (mammalian) fast muscle fibres

    PubMed Central

    Roots, H.

    2008-01-01

    We examined, over a wide range of temperatures (10–35°C), the isometric tension and tension during ramp shortening at different velocities (0.2–4 L0/s) in tetanized intact fibre bundles from a rat fast (flexor hallucis brevis) muscle; fibre length (L0) was 2.2 mm and sarcomere length ~2.5 μm. During a ramp shortening, the tension change showed an initial inflection of small amplitude (P1), followed by a larger exponential decline towards an approximate steady level; the tension continued to decline slowly afterwards and the approximate steady tension at a given velocity was estimated as the tension (P2) at the point of intersection between two linear slopes, as previously described (Roots et al. 2007). At a given temperature, the tension P2 declined to a lower level and at a faster rate (from an exponential curve fit) as the shortening velocity was increased; the temperature sensitivity of the rate of tension decline during ramp shortening at different velocities was low (Q10 0.9–1.5). The isometric tension and the P2 tension at a given shortening velocity increased with warming so that the relation between tension and (reciprocal) temperature was sigmoidal in both. In isometric muscle, the temperature T0.5 for half-maximal tension was ~10°C, activation enthalpy change (∆H) was ~100 kJ mol−1 and entropy change (∆S) ~350 J mol−1 K−1. In shortening, these were increased with increase of velocity so that at a shortening velocity (~4 L0/s) producing maximal power at 35°C, T0.5 was ~28°C, ∆H was ~200 kJ mol−1 and ∆S ~ 700 J mol−1 K−1; the same trends were seen in the tension data from isotonic release experiments on intact muscle and in ramp shortening experiments on maximally Ca-activated skinned fibres. In general, our findings show that the sigmoidal relation between force and temperature can be extended from isometric to shortening muscle; the implications of the findings are discussed in relation to the crossbridge cycle

  14. An analysis of the temperature dependence of force, during steady shortening at different velocities, in (mammalian) fast muscle fibres.

    PubMed

    Roots, H; Ranatunga, K W

    2008-01-01

    We examined, over a wide range of temperatures (10-35 degrees C), the isometric tension and tension during ramp shortening at different velocities (0.2-4 L(0)/s) in tetanized intact fibre bundles from a rat fast (flexor hallucis brevis) muscle; fibre length (L(0)) was 2.2 mm and sarcomere length approximately 2.5 microm. During a ramp shortening, the tension change showed an initial inflection of small amplitude (P(1)), followed by a larger exponential decline towards an approximate steady level; the tension continued to decline slowly afterwards and the approximate steady tension at a given velocity was estimated as the tension (P(2)) at the point of intersection between two linear slopes, as previously described (Roots et al. 2007). At a given temperature, the tension P(2) declined to a lower level and at a faster rate (from an exponential curve fit) as the shortening velocity was increased; the temperature sensitivity of the rate of tension decline during ramp shortening at different velocities was low (Q(10) 0.9-1.5). The isometric tension and the P(2) tension at a given shortening velocity increased with warming so that the relation between tension and (reciprocal) temperature was sigmoidal in both. In isometric muscle, the temperature T(0.5) for half-maximal tension was approximately 10 degrees C, activation enthalpy change (DeltaH) was approximately 100 kJ mol(-1) and entropy change (DeltaS) approximately 350 J mol(-1) K(-1). In shortening, these were increased with increase of velocity so that at a shortening velocity (approximately 4 L(0)/s) producing maximal power at 35 degrees C, T(0.5) was approximately 28 degrees C, DeltaH was approximately 200 kJ mol(-1) and DeltaS approximately 700 J mol(-1) K(-1); the same trends were seen in the tension data from isotonic release experiments on intact muscle and in ramp shortening experiments on maximally Ca-activated skinned fibres. In general, our findings show that the sigmoidal relation between force and

  15. Tumor Necrosis Factor Receptor Associated Factor 2 Signaling Provokes Adverse Cardiac Remodeling in the Adult Mammalian Heart

    PubMed Central

    Divakaran, Vijay G.; Evans, Sarah; Topkara, Veli K.; Diwan, Abhinav; Burchfield, Jana; Gao, Feng; Dong, Jianwen; Tzeng, Huei-Ping; Sivasubramanian, Natarajan; Barger, Philip M.; Mann, Douglas L.

    2013-01-01

    Background Tumor necrosis factor (TNF) superfamily ligands that provoke a dilated cardiac phenotype signal through a common scaffolding protein termed TNF receptor associated factor 2 (TRAF2); however, virtually nothing is known with regard to TRAF2 signaling in the adult mammalian heart. Methods and Results We generated multiple founder lines of mice with cardiac restricted overexpression of TRAF2 and characterized the phenotype of mice with higher expression levels of TRAF2 (MHC-TRAF2HC). MHC-TRAF2HC transgenic mice developed a time-dependent increase in cardiac hypertrophy, LV dilation and adverse LV remodeling, and a significant decrease in LV +dP/dt and −dP/dt when compared to littermate (LM) controls (p < 0.05 compared to LM). During the early phases of LV remodeling there was a significant increase in total matrix metalloproteinase (MMP) activity that corresponded with a decrease in total myocardial fibrillar collagen content. As the MHC-TRAF2HC mice aged, there was a significant decrease in total MMP activity accompanied by an increase in total fibrillar collagen content and an increase in myocardial tissue inhibitor of metalloproteinase-1 levels. There was a significant increase in NF-κB activation at 4 – 12 weeks and JNK activation at 4 weeks in the MHCs TRAF2HC mice. Transciptional profiling revealed that > 95% of the hypertrophic/dilated cardiomyopathy-related genes that were significantly upregulated genes in the MHC-TRAF2HC hearts contained κB elements in their promoters. Conclusions These results show for the first time that targeted overexpression of TRAF2 is sufficient to mediate adverse cardiac remodeling in the heart. PMID:23493088

  16. Regulatory Mechanism of Muscle Disuse Atrophy in Adult Rats

    NASA Technical Reports Server (NTRS)

    1993-01-01

    lowered levels of spermatid formation. Hormonal changes due to testes atrophy must be considered in future experiments where related effects may modify muscle, bone or other tissue changes. Also, some new assessments of past results (published by many researchers) may warrant revised interpretations. The blood pressure studies and the testicular function results were presented and reviewed during an invited lecture at the University of Bordeaux II during the Animals in Space Symposium in March 1993. In summary, each of these three projects complied with the objectives of the proposal and serve to demonstrate the utility of animal models in preparations and interpretations of space flight results. All funding has been expended in accordance with the approved budget.

  17. The effect of habitual exercise on respiratory- muscle function in older adults.

    PubMed

    Watsford, Mark L; Murphy, Aron J; Pine, Matthew J; Coutts, Aaron J

    2005-01-01

    Older adults' participation in habitual exercise might be affected by alterations to respiratory mechanics such as decreased respiratory-muscle strength. This reduction can cause a decrease in efficiency of the ventilatory pump, potentially compromising exercise participation. This research examined the role of habitual exercise in respiratory-muscle function and the associated implications for exercise performance. Seventy-two healthy older adults (36 men, 64.9 +/- 8.6 years, 177.2 +/- 8.4 cm, 82.5+/- 11.9 kg; 36 women, 64.9 +/- 9.5 years, 161.7+/- 6.4 cm, 61.6 +/- 9.2 kg) undertook respiratory-function and walking-performance tests. Active men and women achieved higher scores than their inactive counterparts for all tests except spirometry, where no differences were evident. The results indicate that a significant amount of the elevated fitness level might be accounted for by increased endurance capacity of the inspiratory muscles. Inactive older individuals might be at risk for inadequate respiratory-muscle strength, so interventions should be considered.

  18. MRF4 negatively regulates adult skeletal muscle growth by repressing MEF2 activity

    PubMed Central

    Moretti, Irene; Ciciliot, Stefano; Dyar, Kenneth A.; Abraham, Reimar; Murgia, Marta; Agatea, Lisa; Akimoto, Takayuki; Bicciato, Silvio; Forcato, Mattia; Pierre, Philippe; Uhlenhaut, N. Henriette; Rigby, Peter W. J.; Carvajal, Jaime J.; Blaauw, Bert; Calabria, Elisa; Schiaffino, Stefano

    2016-01-01

    The myogenic regulatory factor MRF4 is highly expressed in adult skeletal muscle but its function is unknown. Here we show that Mrf4 knockdown in adult muscle induces hypertrophy and prevents denervation-induced atrophy. This effect is accompanied by increased protein synthesis and widespread activation of muscle-specific genes, many of which are targets of MEF2 transcription factors. MEF2-dependent genes represent the top-ranking gene set enriched after Mrf4 RNAi and a MEF2 reporter is inhibited by co-transfected MRF4 and activated by Mrf4 RNAi. The Mrf4 RNAi-dependent increase in fibre size is prevented by dominant negative MEF2, while constitutively active MEF2 is able to induce myofibre hypertrophy. The nuclear localization of the MEF2 corepressor HDAC4 is impaired by Mrf4 knockdown, suggesting that MRF4 acts by stabilizing a repressor complex that controls MEF2 activity. These findings open new perspectives in the search for therapeutic targets to prevent muscle wasting, in particular sarcopenia and cachexia. PMID:27484840

  19. The role of diacylglycerol kinase ζ and phosphatidic acid in the mechanical activation of mammalian target of rapamycin (mTOR) signaling and skeletal muscle hypertrophy.

    PubMed

    You, Jae-Sung; Lincoln, Hannah C; Kim, Chan-Ran; Frey, John W; Goodman, Craig A; Zhong, Xiao-Ping; Hornberger, Troy A

    2014-01-17

    The activation of mTOR signaling is essential for mechanically induced changes in skeletal muscle mass, and previous studies have suggested that mechanical stimuli activate mTOR (mammalian target of rapamycin) signaling through a phospholipase D (PLD)-dependent increase in the concentration of phosphatidic acid (PA). Consistent with this conclusion, we obtained evidence which further suggests that mechanical stimuli utilize PA as a direct upstream activator of mTOR signaling. Unexpectedly though, we found that the activation of PLD is not necessary for the mechanically induced increases in PA or mTOR signaling. Motivated by this observation, we performed experiments that were aimed at identifying the enzyme(s) that promotes the increase in PA. These experiments revealed that mechanical stimulation increases the concentration of diacylglycerol (DAG) and the activity of DAG kinases (DGKs) in membranous structures. Furthermore, using knock-out mice, we determined that the ζ isoform of DGK (DGKζ) is necessary for the mechanically induced increase in PA. We also determined that DGKζ significantly contributes to the mechanical activation of mTOR signaling, and this is likely driven by an enhanced binding of PA to mTOR. Last, we found that the overexpression of DGKζ is sufficient to induce muscle fiber hypertrophy through an mTOR-dependent mechanism, and this event requires DGKζ kinase activity (i.e. the synthesis of PA). Combined, these results indicate that DGKζ, but not PLD, plays an important role in mechanically induced increases in PA and mTOR signaling. Furthermore, this study suggests that DGKζ could be a fundamental component of the mechanism(s) through which mechanical stimuli regulate skeletal muscle mass.

  20. Diminished Foot and Ankle Muscle Volumes in Young Adults With Chronic Ankle Instability

    PubMed Central

    Feger, Mark A.; Snell, Shannon; Handsfield, Geoffrey G.; Blemker, Silvia S.; Wombacher, Emily; Fry, Rachel; Hart, Joseph M.; Saliba, Susan A.; Park, Joseph S.; Hertel, Jay

    2016-01-01

    Background: Patients with chronic ankle instability (CAI) have demonstrated altered neuromuscular function and decreased muscle strength when compared with healthy counterparts without a history of ankle sprain. Up to this point, muscle volumes have not been analyzed in patients with CAI to determine whether deficits in muscle size are present following recurrent sprain. Purpose: To analyze intrinsic and extrinsic foot and ankle muscle volumes and 4-way ankle strength in young adults with and without CAI. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Five patients with CAI (mean age, 23.0 ± 4 years; 1 male, 4 females) and 5 healthy controls (mean age, 23.8 ± 4.5 years; 1 male, 4 females) volunteered for this study. Novel fast-acquisition magnetic resonance imaging (MRI) was used to scan from above the femoral condyles through the foot and ankle. The perimeter of each muscle was outlined on each axial slice and then the 2-dimensional area was multiplied by the slice thickness (5 mm) to calculate the muscle volume. Plantar flexion, dorsiflexion, inversion, and eversion isometric strength were measured using a handheld dynamometer. Patients with CAI were compared with healthy controls on all measures of muscle volume and strength. Extrinsic muscle volumes of patients with CAI were also compared with a normative database of healthy controls (n = 24) by calculating z scores for each muscle individually for each CAI subject. Results: The CAI group had smaller total shank, superficial posterior compartment, soleus, adductor hallucis obliqus, and flexor hallucis brevis muscle volumes compared with healthy controls as indicated by group means and associated 90% CIs that did not overlap. Cohen d effect sizes for the significant group differences were all large and ranged from 1.46 to 3.52, with 90% CIs that did not cross zero. The CAI group had lower eversion, dorsiflexion, and 4-way composite ankle strength, all with group means and associated 90

  1. Non-genomic mechanism of 17 beta-oestradiol-induced inhibition of contraction in mammalian vascular smooth muscle.

    PubMed Central

    Kitazawa, T; Hamada, E; Kitazawa, K; Gaznabi, A K

    1997-01-01

    17 beta-Oestradiol (E2) at 0.1-10 microM directly inhibited various tonic and phasic smooth muscle contractions. The mechanism(s) of oestrogen-induced inhibition of contraction was studied using intact and permeabilized strips and isolated single cells of smooth muscle. 2. In endothelium-denuded vascular smooth muscle, E2 attenuated high K(+)-induced force development and myosin light chain phosphorylation, and produced rapid and reversible relaxation. There were no significant differences in these inhibitory effects between tissue types (femoral artery vs. portal vein), species (rat vs. rabbit) or sexes. 3. The inhibitory potencies of several steroidal and non-steroidal oestrogen analogues were examined and their effects were for the most part stereo-specific. However, two steroids with negligible affinities for the nuclear oestrogen receptor also strongly inhibited high K(+)-induced contraction. 4. Genomic modulators including a protein synthesis inhibitor, an RNA synthesis inhibitor, and oestrogen receptor antagonists did not affect the inhibitory actions of E2. Inhibitors of cyclic nucleotide-dependent protein kinases did not reduce the E2 effect. 5. Ca2+ release from intracellular stores by agonists and by inositol 1,4,5-trisphosphate (IP3) does not appear to be modulated by E2. Neither pretreatment with ryanodine nor with thapsigargin affected the E2-induced inhibition of high K(+)-induced contraction. 6. E2 had no effect on either normal or GTP gamma S-increased Ca2+ sensitivity of the regulatory and contractile apparatus. 7. E2 and its analogues rapidly inhibited voltage-dependent L-type Ca2+ channel currents in isolated smooth muscle cells. Repetitive stimulation was not required for E2-induced inhibition of the currents. 8. This study strongly suggests that at pharmacological concentrations oestrogen primarily reduces Ca2+ influx through inhibition of L-type Ca2+ channels in a non-genomic manner and decreases myosin light chain phosphorylation and

  2. Muscle Strength, Physical Activity, and Functional Limitations in Older Adults with Central Obesity

    PubMed Central

    Germain, Cassandra M.; Batsis, John A.; Vasquez, Elizabeth; McQuoid, Douglas R.

    2016-01-01

    Background. Obesity and muscle weakness are independently associated with increased risk of physical and functional impairment in older adults. It is unknown whether physical activity (PA) and muscle strength combined provide added protection against functional impairment. This study examines the association between muscle strength, PA, and functional outcomes in older adults with central obesity. Methods. Prevalence and odds of physical (PL), ADL, and IADL limitation were calculated for 6,388 community dwelling adults aged ≥ 60 with central obesity. Individuals were stratified by sex-specific hand grip tertiles and PA. Logistic models were adjusted for age, education, comorbidities, and body-mass index and weighted. Results. Overall prevalence of PL and ADL and IADL limitations were progressively lower by grip category. Within grip categories, prevalence was lower for individuals who were active than those who were inactive. Adjusted models showed significantly lower odds of PL OR 0.42 [0.31, 0.56]; ADL OR 0.60 [0.43, 0.84], and IADL OR 0.46 [0.35, 0.61] for those in the highest grip strength category as compared to those in the lowest grip category. Conclusion. Improving grip strength in obese elders who are not able to engage in traditional exercise is important for reducing odds of physical and functional impairment. PMID:27034833

  3. Muscle mechanical properties of adult and older rats submitted to exercise after immobilization

    PubMed Central

    Kodama, Fábio Yoshikazu; Camargo, Regina Celi Trindade; Job, Aldo Eloizo; Ozaki, Guilherme Akio Tamura; Koike, Tatiana Emy; Camargo Filho, José Carlos Silva

    2012-01-01

    Objectives To describe the effects of immobilization, free remobilization and remobilization by physical exercise about mechanical properties of skeletal muscle of rats of two age groups. Methods 56 Wistar rats divided into two groups according to age, an adult group (five months) and an older group (15 months). These groups were subdivided in: control, immobilized, free remobilized and remobilized by physical exercise. The pelvic limb of rats was immobilized for seven days. The exercise protocol consisted of five swimming sessions, once per day and 25 minutes per session. The gastrocnemius muscle was subjected to tensile tests, and evaluated the properties: load at the maximum limit, stretching at the maximum limit and stiffness. Results The immobilization reduced the values of load at the maximum limit and the remobilization protocols were not sufficient to restore control levels in adult group and older rats. The stretching at the maximum limit differs only in the older group. Conclusions The immobilization reduces the muscle's ability to bear loads and exercise protocol tends to restore the default at control values in adult and older rats. The age factor only interfered in the stretching at the maximum limit, inducing a reduction of this property in the post-immobilization. Level of Evidence II, Investigating the Results of Treatment. PMID:24453606

  4. Myf5 haploinsufficiency reveals distinct cell fate potentials for adult skeletal muscle stem cells.

    PubMed

    Gayraud-Morel, Barbara; Chrétien, Fabrice; Jory, Aurélie; Sambasivan, Ramkumar; Negroni, Elisa; Flamant, Patricia; Soubigou, Guillaume; Coppée, Jean-Yves; Di Santo, James; Cumano, Ana; Mouly, Vincent; Tajbakhsh, Shahragim

    2012-04-01

    Skeletal muscle stem cell fate in adult mice is regulated by crucial transcription factors, including the determination genes Myf5 and Myod. The precise role of Myf5 in regulating quiescent muscle stem cells has remained elusive. Here we show that most, but not all, quiescent satellite cells express Myf5 protein, but at varying levels, and that resident Myf5 heterozygous muscle stem cells are more primed for myogenic commitment compared with wild-type satellite cells. Paradoxically however, heterotypic transplantation of Myf5 heterozygous cells into regenerating muscles results in higher self-renewal capacity compared with wild-type stem cells, whereas myofibre regenerative capacity is not altered. By contrast, Pax7 haploinsufficiency does not show major modifications by transcriptome analysis. These observations provide a mechanism linking Myf5 levels to muscle stem cell heterogeneity and fate by exposing two distinct and opposing phenotypes associated with Myf5 haploinsufficiency. These findings have important implications for how stem cell fates can be modulated by crucial transcription factors while generating a pool of responsive heterogeneous cells.

  5. Force generation examined by laser temperature-jumps in shortening and lengthening mammalian (rabbit psoas) muscle fibres.

    PubMed

    Ranatunga, K W; Coupland, M E; Pinniger, G J; Roots, H; Offer, G W

    2007-11-15

    We examined the tension change induced by a rapid temperature jump (T-jump) in shortening and lengthening active muscle fibres. Experiments were done on segments of permeabilized single fibres (length (L0) approximately 2 mm, sarcomere length 2.5 microm) from rabbit psoas muscle; [MgATP] was 4.6 mm, pH 7.1, ionic strength 200 mm and temperature approximately 9 degrees C. A fibre was maximally Ca2+-activated in the isometric state and a approximately 3 degrees C, rapid (< 0.2 ms), laser T-jump applied when the tension was approximately steady in the isometric state, or during ramp shortening or ramp lengthening at a limited range of velocities (0-0.2 L0 s(-1)). The tension increased to 2- to 3 x P0 (isometric force) during ramp lengthening at velocities > 0.05 L0 s(-1), whereas the tension decreased to about < 0.5 x P0 during shortening at 0.1-0.2 L0 s(-1); the unloaded shortening velocity was approximately 1 L0 s(-1) and the curvature of the force-shortening velocity relation was high (a/P0 ratio from Hill's equation of approximately 0.05). In isometric state, a T-jump induced a tension rise of 15-20% to a new steady state; by curve fitting, the tension rise could be resolved into a fast (phase 2b, 40-50 s(-1)) and a slow (phase 3, 5-10 s(-1)) exponential component (as previously reported). During steady lengthening, a T-jump induced a small instantaneous drop in tension, followed by recovery, so that the final tension recorded with and without a T-jump was not significantly different; thus, a T-jump did not lead to a net increase of tension. During steady shortening, the T-jump induced a pronounced tension rise and both its amplitude and the rate (from a single exponential fit) increased with shortening velocity; at 0.1-0.2 L0 s(-1), the extent of fibre shortening during the T-jump tension rise was estimated to be approximately 1.2% L(0) and it was shorter at lower velocities. At a given shortening velocity and over the temperature range of 8-30 degrees C, the

  6. Improved knee extensor strength with resistance training associates with muscle specific miRNAs in older adults.

    PubMed

    Zhang, Tan; Birbrair, Alexander; Wang, Zhong-Min; Messi, María L; Marsh, Anthony P; Leng, Iris; Nicklas, Barbara J; Delbono, Osvaldo

    2015-02-01

    Regular exercise, particularly resistance training (RT), is the only therapy known to consistently improve muscle strength and quality (force per unit of mass) in older persons, but there is considerable variability in responsiveness to training. Identifying sensitive diagnostic biomarkers of responsiveness to RT may inform the design of a more efficient exercise regimen to improve muscle strength in older adults. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. We quantified six muscle specific miRNAs (miR-1, -133a, -133b, -206, -208b and -499) in both muscle tissue and blood plasma, and their relationship with knee extensor strength in seven older (age=70.5 ± 2.5 years) adults before and after 5 months of RT. MiRNAs differentially responded to RT; muscle miR-133b decreased, while all plasma miRNAs tended to increase. Percent changes in knee extensor strength with RT showed strong positive correlations with percent changes in muscle miR-133a, -133b, and -206 and with percent changes in plasma and plasma/muscle miR-499 ratio. Baseline level of plasma or plasma/muscle miR-499 ratio further predicts muscle response to RT, while changes in muscle miR-133a, -133b, and -206 may correlate with muscle TNNT1 gene alternative splicing in response to RT. Our results indicate that RT alters muscle specific miRNAs in muscle and plasma, and that these changes account for some of the variation in strength responses to RT in older adults.

  7. Improved Knee Extensor Strength with Resistance Training Associates with Muscle Specific miRNAs in Older Adults

    PubMed Central

    Zhang, Tan; Birbrair, Alexander; Wang, Zhong-Min; Messi, María L.; Marsh, Anthony P.; Leng, Iris; Nicklas, Barbara J.; Delbono, Osvaldo

    2015-01-01

    Regular exercise, particularly resistance training (RT), is the only therapy known to consistently improve muscle strength and quality (force per unit of mass) in older persons, but there is considerable variability in responsiveness to training. Identifying sensitive diagnostic biomarkers of responsiveness to RT may inform the design of a more efficient exercise regimen to improve muscle strength in older adults. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. We quantified six muscle specific miRNAs (miR-1, -133a, -133b, -206, -208b and -499) in both muscle tissue and blood plasma, and their relationship with knee extensor strength in seven older (age = 70.5 ± 2.5 years) adults before and after 5 months of RT. MiRNAs differentially responded to RT; muscle miR-133b decreased, while all plasma miRNAs tended to increase. Percent changes in knee extensor strength with RT showed strong positive correlations with percent changes in muscle miR-133a, -133b, -206 and with percent changes in plasma and plasma/muscle miR-499 ratio. Baseline level of plasma or plasma/muscle miR-499 ratio further predicts muscle response to RT, while changes in muscle miR-133a, -133b, -206 may correlate with muscle TNNT1gene alternative splicing in response to RT. Our results indicate that RT alters muscle specific miRNAs in muscle and plasma, and that these changes account for some of the variation in strength responses to RT in older adults. PMID:25560803

  8. Peeled mammalian skeletal muscle fibers. Possible stimulation of Ca2+ release via a transverse tubule-sarcoplasmic reticulum mechanism

    PubMed Central

    1985-01-01

    Single muscle fibers from rabbit soleus and adductor magnus and from semitendinosus muscles were peeled to remove the sarcolemma and then stimulated to release Ca2+ by (a) caffeine application or (b) ionic depolarization accomplished via substitution of choline chloride for potassium propionate at constant [K+] X [Cl-] in the bathing solution. Each stimulus, ionic or caffeine, elicited an isometric tension transient that appeared to be due to Ca2+ released from the sarcoplasmic reticulum (SR). The peak magnitude of the ionic (Cl- - induced) tension transient increased with increasing Cl- concentration. The application of ouabain to fibers after peeling had no effect on either type of tension transient. However, soaking the fibers in a ouabain solution before peeling blocked the Cl- -induced but not the caffeine-induced tension transient, which suggests that ouabain's site of action is extracellular, perhaps inside transverse tubules (TTs). Treating the peeled fibers with saponin, which should disrupt TTs to a greater extent than SR membrane, greatly reduced or eliminated the Cl- - induced tension transient without significantly altering the caffeine- induced tension transient. These results suggest that the Cl- -induced tension transient is elicited via stimulation of sealed, polarized TTs rather than via ionic depolarization of the SR. PMID:4056734

  9. Whole-cell patch-clamp recording of nicotinic acetylcholine receptors in adult Brugia malayi muscle

    PubMed Central

    Robertson, A. P.; Buxton, S. K.; Martin, R. J.

    2013-01-01

    Lymphatic filariasis is a debilitating disease caused by clade III parasites like Brugia malayi and Wuchereria bancrofti. Current recommended treatment regimen for this disease relies on albendazole, ivermectin and diethylcarbamazine, none of which targets the nicotinic acetylcholine receptors in these parasitic nematodes. Our aim therefore has been to develop adult B. malayi for electrophysiological recordings to aid in characterizing the ion channels in this parasite as anthelmintic target sites. In that regard, we recently demonstrated the amenability of adult B. malayi to patch-clamp recordings and presented results on the single-channel properties of nAChR in this nematode. We have built on this by recording whole-cell nAChR currents from adult B. malayi muscle. Acetylcholine, levamisole, pyrantel, bephenium and tribendimidine activated the receptors on B. malayi muscle, producing robust currents ranging from > 200 pA to ~1.5 nA. Levamisole completely inhibited motility of the adult B. malayi within 10 min and after 60 min, motility had recovered back to control values. PMID:23562945

  10. Cardiac muscle plasticity in adult and embryo by heart-derived progenitor cells.

    PubMed

    Oh, Hidemasa; Chi, Xuan; Bradfute, Steven B; Mishina, Yuji; Pocius, Jennifer; Michael, Lloyd H; Behringer, Richard R; Schwartz, Robert J; Entman, Mark L; Schneider, Michael D

    2004-05-01

    The evidence of cardiomyocyte proliferation in damaged heart implied cardiac regeneration might occur by resident or extra cardiac stem cells. However, the specification and origin of these cells remain unknown. Here, we report using fluorescence-activated cell sorting that cardiac progenitor cells resided in adult heart and colocalized with small capillary vessels, within the stem cell antigen (Sca-1) population expressing high telomerase activity. Notably, hematopoietic stem cells capable of efflux Hoechst 33342, termed side population cells, also were identified within the heart-derived cells. The cardiac progenitor cells (CD45(-)/CD34(-)) express neither cardiac muscle nor endothelial cell markers at an undifferentiated stage. The exposure of 5-azacytidine induced cardiac differentiation, which depends, in part, on Bmpr1a, a type IA receptor for bone morphogenetic protein (BMP). The capability of adult Sca1(+) cells to adopt a cardiac muscle in embryogenesis was substantiated by blastocyst injection, using progenitors from the adult hearts of transgenic mice that harbor a bacterial artificial chromosome expressing GFP via the Nkx-2.5 locus. Intravenously injected progenitors, shortly after ischemic/reperfusion, homed and functionally differentiated 3.5% of total left ventricle in the host myocardium. Differentiation included both fusion-independent and fusion-associated components, proved by the Cre/loxP donor/recipient system. Our studies suggest that endogenous cardiac progenitors reside in the adult heart, regenerate cardiomyocytes functionally, and integrate into the existing heart circuitry.

  11. Effects of chronic overload on muscle hypertrophy and mTOR signaling in adult and aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined the effect of 28 days of overload on mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling in young adult (Y; 6 mo old) and aged (O; 30 mo old) Fischer 344 x Brown Norway rats subjected to bilateral synergist ablation (SA) of two-thirds of the gas...

  12. Preparation and Culture of Myogenic Precursor Cells/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans.

    PubMed

    Soriano-Arroquia, Ana; Clegg, Peter D; Molloy, Andrew P; Goljanek-Whysall, Katarzyna

    2017-02-16

    Skeletal muscle homeostasis depends on muscle growth (hypertrophy), atrophy and regeneration. During ageing and in several diseases, muscle wasting occurs. Loss of muscle mass and function is associated with muscle fiber type atrophy, fiber type switching, defective muscle regeneration associated with dysfunction of satellite cells, muscle stem cells, and other pathophysiological processes. These changes are associated with changes in intracellular as well as local and systemic niches. In addition to most commonly used rodent models of muscle ageing, there is a need to study muscle homeostasis and wasting using human models, which due to ethical implications, consist predominantly of in vitro cultures. Despite the wide use of human Myogenic Progenitor Cells (MPCs) and primary myoblasts in myogenesis, there is limited data on using human primary myoblast and myotube cultures to study molecular mechanisms regulating different aspects of age-associated muscle wasting, aiding in the validation of mechanisms of ageing proposed in rodent muscle. The use of human MPCs, primary myoblasts and myotubes isolated from adult and aged people, provides a physiologically relevant model of molecular mechanisms of processes associated with muscle growth, atrophy and regeneration. Here we describe in detail a robust, inexpensive, reproducible and efficient protocol for the isolation and maintenance of human MPCs and their progeny - myoblasts and myotubes from human muscle samples using enzymatic digestion. Furthermore, we have determined the passage number at which primary myoblasts from adult and aged people undergo senescence in an in vitro culture. Finally, we show the ability to transfect these myoblasts and the ability to characterize their proliferative and differentiation capacity and propose their suitability for performing functional studies of molecular mechanisms of myogenesis and muscle wasting in vitro.

  13. Stress in the Adult Rat Exacerbates Muscle Pain Induced by Early-Life Stress

    PubMed Central

    Alvarez, Pedro; Green, Paul G.; Levine, Jon D.

    2013-01-01

    Background Early-life stress and exposure to stressful stimuli play a major role in the development of chronic widespread pain in adults. However, how they interact in chronic pain syndromes remains unclear. Methods Dams and neonatal litters were submitted to a restriction of nesting material (neonatal limited bedding, NLB) for one week. As adults, these rats were exposed to a painless sound stress protocol. The involvement of sympathoadrenal catecholamines, interleukin 6 (IL-6) and tumor necrosis alpha (TNFα) in nociception, was evaluated through of behavioral and ELISA assays, surgical interventions and intrathecal antisense treatments. Results Adult NLB rats exhibited mild muscle hyperalgesia, which was markedly aggravated by sound stress (peaking 15 days after exposure). Adrenal medullectomy did not modify hyperalgesia in NLB rats but prevented its aggravation by sound stress. Sustained administration of epinephrine to NLB rats mimicked sound stress effect. Intrathecal treatment with antisense directed to IL-6-receptor subunit gp130, but not to TNFα type 1 receptor (TNFR1), inhibited hyperalgesia in NLB rats. However, antisense against either gp130 or TNFR1 inhibited sound stress-induced enhancement of hyperalgesia. Compared to control rats, NLB rats exhibit increased plasma levels of IL-6 but decreased levels of TNFα, whereas sound stress increases IL-6 plasma levels in control but not in NLB rats. Conclusions Early-life stress induces a persistent elevation of IL-6, hyperalgesia and susceptibility to chronic muscle pain, which is unveiled by exposure to stress in adults. This probably depends on an interaction between adrenal catecholamines and pro-inflammatory cytokines acting at muscle nociceptor level. PMID:23706525

  14. Muscle activation and energy expenditure of sedentary behavior alternatives in young and old adults.

    PubMed

    Lerma, Nicholas L; Keenan, Kevin G; Strath, Scott J; Forseth, Bethany M; Cho, Chi C; Swartz, Ann M

    2016-09-21

    The physiological mechanisms that underlie the metabolic benefits of breaking up sedentary behavior (SB) have yet to be determined. The purpose of this study is to compare energy expenditure (EE) and muscle activation (MA) responses to sitting and four SB alternatives in younger and older adults. Twenty-two adults, grouped by age (21-35 and 62-76 years), completed five randomly ordered 20 min tasks: (1) continuous sitting (Sit), (2) sitting on a stability ball (Ball), (3) continuous standing (Stand), (4) sitting interrupted by walking (S/W), and (5) sitting interrupted by standing (S/S). Muscle activation of two upper (trapezius and erector spinae) and two lower (rectus femoris and medial gastrocnemius) body muscles and total body EE were measured continuously. A linear mixed model using gender and age as a covariate with Bonferroni adjustment were used to determine significant differences between tasks. Collectively, S/W produced significantly higher MA and EE compared with Sit (p  <  0.001). Stand and Ball provided significantly greater EE, but not MA, compared to Sit (p  <  0.05), while S/S did not significantly change EE or MA compared to Sit. There were no net EE differences when comparing age groups across the tasks. Upper body MA was not consistent in both age groups across tasks. Specifically, during S/W the upper body MA of older adults (9.7  ±  1.5% MVC) was double that of young adults (4.8  ±  0.7% MVC, p  =  0.006). Lower body MA responded similarly to all tasks in both age groups. Disrupting sitting with walking produced the largest increase in EE and MA compared to other SB alternatives in both age groups. These results are important considering the wide use of SB alternatives by researchers and public health practitioners.

  15. Excitable properties of adult skeletal muscle fibres from the honeybee Apis mellifera.

    PubMed

    Collet, Claude; Belzunces, Luc

    2007-02-01

    In the hive, a wide range of honeybees tasks such as cell cleaning, nursing, thermogenesis, flight, foraging and inter-individual communication (waggle dance, antennal contact and trophallaxy) depend on proper muscle activity. However, whereas extensive electrophysiological studies have been undertaken over the past ten years to characterize ionic currents underlying the physiological neuronal activity in honeybee, ionic currents underlying skeletal muscle fibre activity in this insect remain, so far, unexplored. Here, we show that, in contrast to many other insect species, action potentials in muscle fibres isolated from adult honeybee metathoracic tibia, are not graded but actual all-or-none responses. Action potentials are blocked by Cd(2+) and La(3+) but not by tetrodotoxin (TTX) in current-clamp mode of the patch-clamp technique, and as assessed under voltage-clamp, both Ca(2+) and K(+) currents are involved in shaping action potentials in single muscle fibres. The activation threshold potential for the voltage-dependent Ca(2+) current is close to -40 mV, its mean maximal amplitude is -8.5+/-1.9 A/F and the mean apparent reversal potential is near +40 mV. In honeybees, GABA does not activate any ionic membrane currents in muscle fibres from the tibia, but L-glutamate, an excitatory neurotransmitter at the neuromuscular synapse induces fast activation of an inward current when the membrane potential is voltage clamped close to its resting value. Instead of undergoing desensitization as is the case in many other preparations, a component of this glutamate-activated current has a sustained component, the reversal potential of which is close to 0 mV, as demonstrated with voltage ramps. Future investigations will allow extensive pharmacological characterization of membrane ionic currents and excitation-contraction coupling in skeletal muscle from honeybee, a useful insect that became a model to study many physiological phenomena and which plays a major role in

  16. Prolongation of Relaxation Time in Extraocular Muscles With Brain Derived Neurotrophic Factor in Adult Rabbit

    PubMed Central

    Nelson, Krysta R.; Stevens, Shanlee M.; McLoon, Linda K.

    2016-01-01

    Purpose We tested the hypothesis that short-term treatment with brain derived neurotrophic factor (BDNF) would alter the contractile characteristics of rabbit extraocular muscle (EOM). Methods One week after injections of BDNF in adult rabbit superior rectus muscles, twitch properties were determined in treated and control muscles in vitro. Muscles were also examined for changes in mean cross-sectional areas, neuromuscular junction size, and percent of myofibers expressing specific myosin heavy chain isoforms, and sarcoendoplasmic reticulum calcium ATPases (SERCA) 1 and 2. Results Brain derived neurotrophic factor–treated muscles had prolonged relaxation times compared with control muscles. Time to 50% relaxation, time to 100% relaxation, and maximum rate of relaxation were increased by 24%, 27%, and 25%, respectively. No significant differences were seen in time to peak force, twitch force, or maximum rate of contraction. Brain derived neurotrophic factor treatment significantly increased mean cross-sectional areas of slow twitch and tonic myofibers, with increased areas ranging from 54% to 146%. Brain derived neurotrophic factor also resulted in an increased percentage of slow twitch myofibers in the orbital layers, ranging from 54% to 77%, and slow-tonic myofibers, ranging from 44% to 62%. No significant changes were seen SERCA1 or 2 expression or in neuromuscular junction size. Conclusions Short-term treatment with BDNF significantly prolonged the duration and rate of relaxation time and increased expression of both slow-twitch and slow-tonic myosin-expressing myofibers without changes in neuromuscular junctions or SERCA expression. The changes induced by BDNF treatment might have potential therapeutic value in dampening/reducing uncontrolled eye oscillations in nystagmus. PMID:27802489

  17. MicroRNA-29a in Adult Muscle Stem Cells Controls Skeletal Muscle Regeneration During Injury and Exercise Downstream of Fibroblast Growth Factor-2.

    PubMed

    Galimov, Artur; Merry, Troy L; Luca, Edlira; Rushing, Elisabeth J; Mizbani, Amir; Turcekova, Katarina; Hartung, Angelika; Croce, Carlo M; Ristow, Michael; Krützfeldt, Jan

    2016-03-01

    The expansion of myogenic progenitors (MPs) in the adult muscle stem cell niche is critical for the regeneration of skeletal muscle. Activation of quiescent MPs depends on the dismantling of the basement membrane and increased access to growth factors such as fibroblast growth factor-2 (FGF2). Here, we demonstrate using microRNA (miRNA) profiling in mouse and human myoblasts that the capacity of FGF2 to stimulate myoblast proliferation is mediated by miR-29a. FGF2 induces miR-29a expression and inhibition of miR-29a using pharmacological or genetic deletion decreases myoblast proliferation. Next generation RNA sequencing from miR-29a knockout myoblasts (Pax7(CE/+) ; miR-29a(flox/flox) ) identified members of the basement membrane as the most abundant miR-29a targets. Using gain- and loss-of-function experiments, we confirm that miR-29a coordinately regulates Fbn1, Lamc1, Nid2, Col4a1, Hspg2 and Sparc in myoblasts in vitro and in MPs in vivo. Induction of FGF2 and miR-29a and downregulation of its target genes precedes muscle regeneration during cardiotoxin (CTX)-induced muscle injury. Importantly, MP-specific tamoxifen-induced deletion of miR-29a in adult skeletal muscle decreased the proliferation and formation of newly formed myofibers during both CTX-induced muscle injury and after a single bout of eccentric exercise. Our results identify a novel miRNA-based checkpoint of the basement membrane in the adult muscle stem cell niche. Strategies targeting miR-29a might provide useful clinical approaches to maintain muscle mass in disease states such as ageing that involve aberrant FGF2 signaling.

  18. The all-or-none role of innervation in expression of apamin receptor and of apamin-sensitive Ca2+-activated K+ channel in mammalian skeletal muscle.

    PubMed

    Schmid-Antomarchi, H; Renaud, J F; Romey, G; Hugues, M; Schmid, A; Lazdunski, M

    1985-04-01

    The long-lasting after-hyperpolarization(s) (AHP) that follows the action potential in rat myotubes differentiated in culture is due to Ca2+-activated K+ channels. These channels have the property to be specifically blocked by the bee venom toxin apamin at low concentrations. Apamin has been used in this work to analyze, by electrophysiological and biochemical techniques, the role of innervation in expression of these important channels. The main results are as follows: (i) Long-lasting AHP that follows the action potential in rat myotubes in culture disappears when myotubes are cocultured with nerve cells from the spinal cord under the conditions of in vitro innervation. (ii) Extensor digitorum longus muscles from adult rats have action potentials that are not followed by AHP but AHP are systematically recorded after muscle denervation and they are blocked by apamin. (iii) Specific 125I-labeled apamin binding is undetectable in innervated muscle fibers but it becomes detectable 2-4 days after muscle denervation to be maximal 10 days after denervation. (iv) Apamin receptors detected with 125I-labeled apamin are present at fetal stages with biochemical characteristics identical to those found in myotubes in culture. The receptor number decreases as maturation proceeds and 125I-labeled apamin receptors completely disappear after the first week of postnatal life, in parallel with the disappearance of multi-innervation. All these results taken together strongly suggest an all-or-none effect of innervation on the expression of apamin-sensitive Ca2+-activated K+ channels.

  19. Recruitment and derecruitment characteristics of motor units in a hand muscle of young and old adults.

    PubMed

    Jesunathadas, Mark; Marmon, Adam R; Gibb, James M; Enoka, Roger M

    2010-06-01

    The significant decline in motor neuron number after approximately 60 yr of age is accompanied by a remodeling of the neuromuscular system so that average motor unit force increases and the ability of old adults to produce an intended force declines. One possible explanation for the loss of movement precision is that the remodeling increases the difference in recruitment forces between successively recruited motor units in old adults and this augments force variability at motor unit recruitment. The purpose of the study was to compare the forces and discharge characteristics of motor units in a hand muscle of young and old adults at motor unit recruitment and derecruitment. The difference in recruitment force between pairs of motor units did not differ between young (n=54) and old adults (n=56; P=0.702). However, old adults had a greater proportion of contractions in which motor units discharged action potentials transiently before discharging continuously during the ramp increase in force (young: 0.32; old: 0.41; P=0.045). Force variability at motor unit recruitment was greater for old adults compared with young adults (Por=0.729). These results suggest that the difference in force between the recruitment of successive motor units does not differ between age groups, but that motor unit recruitment may be more transient and could contribute to the greater variability in force observed in old adults during graded ramp contractions.

  20. Bradykinin-related peptides (BRPs) from skin secretions of three genera of phyllomedusine leaf frogs and their comparative pharmacological effects on mammalian smooth muscles.

    PubMed

    Jiang, Yingchun; Xi, Xinping; Ge, Lilin; Yang, Nan; Hou, Xiaojuan; Ma, Jie; Ma, Chengbang; Wu, Yuxin; Guo, Xiaoxiao; Li, Renjie; Zhou, Mei; Wang, Lei; Chen, Tianbao; Shaw, Chris

    2014-02-01

    While bradykinin has been identified in the skin secretions from several species of amphibian, bradykinin-related peptides (BRPs) are more common constituents. These peptides display a plethora of primary structural variations from the type peptide which include single or multiple amino acid substitutions, N- and/or C-terminal extensions and post-translational modifications such as proline hydroxylation and tyrosine sulfation. Such modified peptides have been reported in species from many families, including Bombinatoridae, Hylidae and Ranidae. The spectrum of these peptides in a given species is thought to be reflective of its predator profile from different vertebrate taxa. Here we report the isolation of BRPs and parallel molecular cloning of their respective biosynthetic precursor-encoding cDNAs from the skin secretions of the Mexican leaf frog (Pachymedusa dacnicolor), the Central American red-eyed leaf frog (Agalychnis callidryas) and the South American orange-legged leaf frog (Phyllomedusa hypochondrialis). Additionally, the eight different BRPs identified were chemically synthesized and screened for bioactivity using four different mammalian smooth muscle preparations and their effects and rank potencies were found to be radically different in these with some acting preferentially through bradykinin B1-type receptors and others through B(2)-type receptors.

  1. Effect of supplemental dietary zinc on the mammalian target of rapamycin (mTOR) signaling pathway in skeletal muscle and liver from post-absorptive mice.

    PubMed

    McClung, James P; Tarr, Tyson N; Barnes, Brian R; Scrimgeour, Angus G; Young, Andrew J

    2007-07-01

    Zinc (Zn) is an essential trace element that functions in cellular signaling. The mammalian target of rapamycin (mTOR) regulates the initiation of protein synthesis. The objective of this study was to determine whether Zn could stimulate protein phosphorylation in the mTOR pathway in vivo. Mice (C57BL/6J, n = 30) were fed Zn marginal diets (ZM, 5 mg/kg) for 4 weeks, followed by fasting (F) and/or refeeding with ZM or Zn supplemental (300 mg/kg, ZS) diets for 3 or 6 h. Plasma insulin was greater (P < 0.05) in refed animals as compared to F animals. Protein phosphorylation was detected using multiplex analysis and Western blotting. Multiplex analysis indicated greater (P < 0.05) p70 S6 kinase (p70S6K) and glycogen synthase kinase 3 (GSK-3 alpha/beta) phosphorylation in livers from 6-h refed ZS animals as compared to F animals. Western blots indicated increased (P < 0.05) Akt (Ser 473) phosphorylation in skeletal muscle from animals refed ZS diets for 3 and 6 h as compared to F animals. The ZS diet affected phosphorylation of GSK-3 (alpha/beta) in liver, as 3-h ZS refed animals had greater (P < 0.01) phosphorylation than F animals. These findings indicate that Zn may contribute to the initiation of protein synthesis as a signaling molecule in vivo.

  2. Pten is necessary for the quiescence and maintenance of adult muscle stem cells

    PubMed Central

    Yue, Feng; Bi, Pengpeng; Wang, Chao; Shan, Tizhong; Nie, Yaohui; Ratliff, Timothy L.; Gavin, Timothy P.; Kuang, Shihuan

    2017-01-01

    Satellite cells (SCs) are myogenic stem cells required for regeneration of adult skeletal muscles. A proper balance among quiescence, activation and differentiation is essential for long-term maintenance of SCs and their regenerative function. Here we show a function of Pten (phosphatase and tensin homologue) in quiescent SCs. Deletion of Pten in quiescent SCs leads to their spontaneous activation and premature differentiation without proliferation, resulting in depletion of SC pool and regenerative failure. However, prior to depletion, Pten-null activated SCs can transiently proliferate upon injury and regenerate injured muscles, but continually decline during regeneration, suggesting an inability to return to quiescence. Mechanistically, Pten deletion increases Akt phosphorylation, which induces cytoplasmic translocation of FoxO1 and suppression of Notch signalling. Accordingly, constitutive activation of Notch1 prevents SC depletion despite Pten deletion. Our findings delineate a critical function of Pten in maintaining SC quiescence and reveal an interaction between Pten and Notch signalling. PMID:28094257

  3. Analytes and Metabolites Associated with Muscle Quality in Young, Healthy Adults

    PubMed Central

    LUSTGARTEN, MICHAEL S.; PRICE, LORI LYN; FIELDING, ROGER A.

    2016-01-01

    Purpose Identification of mechanisms that underlie lower extremity muscle quality (leg press one repetition maximum/total lean mass; LP/Lean) may be important for individuals interested in optimizing fitness and sport performance. The purpose of the current study was to provide observational insight into mechanisms that may underlie muscle quality by characterizing the association between 286 mass spectrometry metabolites and 17 chemistry screen analytes with LP/Lean in young, healthy adults (N = 77 (49 women and 28 men); mean age, 24.4 ± 4.2 yr; BMI, 23.5 ± 2.6 kg·m−2). Methods Principal components analysis (PCA) was used to reduce the 286 metabolites into 73 metabolite-containing PCA factors. Sex-adjusted linear regression was used to examine the association between PCA factors and chemistry screen analytes with LP/Lean. Q values were computed to account for multiple comparison testing. Stepwise linear regression and leave-one-out cross validation were used to identify a predictor set representative of LP/Lean and to assess internal validity, respectively. Results Metabolites or analytes related to dietary protein intake (albumin, branched-chain amino acids (BCAA)) and excitation-contraction coupling (calcium and magnesium) were positively associated, whereas metabolites related to gut bacterial metabolism (cinnamoylglycine, hydrocinnamate, hippurate, indolepropionate) and peroxisome proliferator–activated receptor-alpha (PPAR-α) (methylglutarylcarnitine and cinnamoylglycine) activation were negatively associated with LP/Lean. Use of leave-one-out cross validation identified magnesium, sex, and the PCA factors containing BCAAs and methionine and methylglutarylcarnitine to be present in more than 90% of the stepwise regression models, thereby explaining 26.7% of the variance (adjusted R2) inherent in muscle quality. Conclusion Collectively, these data suggest that mechanisms related to dietary protein intake, excitation-contraction coupling, gut microbial

  4. Isolation and Culture of Individual Myofibers and their Satellite Cells from Adult Skeletal Muscle

    PubMed Central

    Pasut, Alessandra; Jones, Andrew E.; Rudnicki, Michael A.

    2013-01-01

    Muscle regeneration in the adult is performed by resident stem cells called satellite cells. Satellite cells are defined by their position between the basal lamina and the sarcolemma of each myofiber. Current knowledge of their behavior heavily relies on the use of the single myofiber isolation protocol. In 1985, Bischoff described a protocol to isolate single live fibers from the Flexor Digitorum Brevis (FDB) of adult rats with the goal to create an in vitro system in which the physical association between the myofiber and its stem cells is preserved 1. In 1995, Rosenblattmodified the Bischoff protocol such that myofibers are singly picked and handled separately after collagenase digestion instead of being isolated by gravity sedimentation 2, 3. The Rosenblatt or Bischoff protocol has since been adapted to different muscles, age or conditions 3-6. The single myofiber isolation technique is an indispensable tool due its unique advantages. First, in the single myofiber protocol, satellite cells are maintained beneath the basal lamina. This is a unique feature of the protocol as other techniques such as Fluorescence Activated Cell Sorting require chemical and mechanical tissue dissociation 7. Although the myofiber culture system cannot substitute for in vivo studies, it does offer an excellent platform to address relevant biological properties of muscle stem cells. Single myofibers can be cultured in standard plating conditions or in floating conditions. Satellite cells on floating myofibers are subjected to virtually no other influence than the myofiber environment. Substrate stiffness and coating have been shown to influence satellite cells' ability to regenerate muscles 8, 9 so being able to control each of these factors independently allows discrimination between niche-dependent and -independent responses. Different concentrations of serum have also been shown to have an effect on the transition from quiescence to activation. To preserve the quiescence state of

  5. Regulation of cell calcium and contractility in mammalian arterial smooth muscle: the role of sodium-calcium exchange.

    PubMed Central

    Ashida, T; Blaustein, M P

    1987-01-01

    1. The contraction and relaxation of rings of rat thoracic aorta and bovine tail artery were examined as a function of changes in the Na+ electrochemical gradient in order to determine the role of Na-Ca exchange in the control of contractility. 2. Inhibition of the Na+ pump in rat aorta by K+-free media or a low concentration (5 x 10(-5) M) of strophanthidin reversibly increased the contractile responses to caffeine and noradrenaline. These effects were dependent upon external Ca2+ and were observed even in the presence of a Ca2+ channel blocker (10 microM-verapamil or 10 microM-diltiazem) and an alpha-receptor blocker (10 microM-phentolamine). 3. Reduction of external Na+ concentration, [Na+]o (replaced by N-methylglucamine, tetramethylammonium or Tris), also caused an external Ca2+-dependent increase in tonic tension and, in rat aorta, an increase in the response to caffeine. These effects were also observed in the presence of verapamil and phentolamine. 4. Caffeine relaxed the bovine tail artery, but increased the sensitivity of the rat aorta to reduced [Na+]o. The latter effect was presumably due to block of Ca2+ sequestration in the sarcoplasmic reticulum, so that entering Ca2+ was more effective in raising the intracellular free Ca2+ level, [Ca2+]i. 5. Relaxation from K+-free or low-Na+ contractions, in Ca2+-free media, depended upon [Na+]o. Reduction of [Na+]o to 1.2 or 7.5 mM slowed the relaxation of rat aorta (5 mM-caffeine present) 3- to 5-fold, and the relaxation of bovine tail artery (without caffeine) 5- to 10-fold. These effects were seen in the presence of verapamil and phentolamine. 6. These observations are all consistent with an Na-Ca exchange transport system that can move Ca2+ either into or out of the arterial smooth muscle cells. Ca2+ entry is enhanced by raising [Na+]i (by Na+ pump inhibition) and/or lowering [Na+]o. Ca2+ extrusion from the contracted muscles is largely dependent upon external Na+. The latter observation implies that, when

  6. Longitudinal decline of lower extremity muscle power in healthy and mobility-limited older adults: influence of muscle mass, strength, composition, neuromuscular activation and single fiber contractile properties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This longitudinal study examined the major physiological mechanisms that determine the age related loss of lower extremity muscle power in two distinct groups of older humans. We hypothesized that after ~3 years of follow-up, mobility-limited older adults (mean age: 77.2 +/- 4, n = 22, 12 females) w...

  7. Short-term bed rest increases TLR4 and IL-6 expression in skeletal muscle of older adults

    PubMed Central

    Timmerman, Kyle L.; Markofski, Melissa M.; Walker, Dillon K.; Dickinson, Jared M.; Jamaluddin, Mohammad; Brasier, Allan R.; Rasmussen, Blake B.; Volpi, Elena

    2013-01-01

    Bed rest induces significant loss of leg lean mass in older adults. Systemic and tissue inflammation also accelerates skeletal muscle loss, but it is unknown whether inflammation is associated to inactivity-induced muscle atrophy in healthy older adults. We determined if short-term bed rest increases toll-like receptor 4 (TLR4) signaling and pro-inflammatory markers in older adult skeletal muscle biopsy samples. Six healthy, older adults underwent seven consecutive days of bed rest. Muscle biopsies (vastus lateralis) were taken after an overnight fast before and at the end of bed rest. Serum cytokine expression was measured before and during bed rest. TLR4 signaling and cytokine mRNAs associated with pro- and anti-inflammation and anabolism were measured in muscle biopsy samples using Western blot analysis and qPCR. Participants lost ∼4% leg lean mass with bed rest. We found that after bed rest, muscle levels of TLR4 protein expression and interleukin-6 (IL-6), nuclear factor-κB1, interleukin-10, and 15 mRNA expression were increased after bed rest (P < 0.05). Additionally, the cytokines interferon-γ, and macrophage inflammatory protein-1β, were elevated in serum samples following bed rest (P < 0.05). We conclude that short-term bed rest in older adults modestly increased some pro- and anti-inflammatory cytokines in muscle samples while systemic changes in pro-inflammatory cytokines were mostly absent. Upregulation of TLR4 protein content suggests that bed rest in older adults increases the capacity to mount an exaggerated, and perhaps unnecessary, inflammatory response in the presence of specific TLR4 ligands, e.g., during acute illness. PMID:23761639

  8. Functional adult acetylcholine receptor develops independently of motor innervation in Sol 8 mouse muscle cell line.

    PubMed Central

    Pinset, C; Mulle, C; Benoit, P; Changeux, J P; Chelly, J; Gros, F; Montarras, D

    1991-01-01

    We have defined culture conditions, using a feeder layer of cells from the embryonic mesenchymal cell line, 10T1/2 and a serum-free medium, which allow cells from the mouse myogenic cell line Sol 8 to form contracting myotubes for two weeks. Under these culture conditions, Sol 8 myotubes undergo a maturation process characterized by a sequential expression of two phenotypes. An early phenotype is typified by the expression of the nicotinic acetylcholine receptor (AChR) gamma-subunit transcripts and the presence of low conductance ACh-activated channels, typical of embryonic AChR. A late phenotype is characterized by the expression of AChR epsilon-subunit transcripts, the decreased accumulation of gamma-subunit transcripts and the appearance of high conductance ACh-activated channels, typical of adult AChR. These results indicate that the expression of functional adult type AChR does not require the presence of the motor nerve and therefore represents an intrinsic feature of the Sol 8 muscle cells. Chronic exposure of the cells to the voltage-sensitive Na+ channel blocking agent tetrodotoxin does not affect the appearance of the AChR epsilon-subunit transcripts but prevents the reduction of the steady-state level of the AChR gamma-subunit transcripts and yields a reduced proportion of the adult type channels. Thus, activity seems to facilitate the switch from the embryonic to the adult phenotype of the AChR protein. The Sol 8 cell system might be useful to analyse further the genetic and epigenetic regulation of muscle fibre maturation in mammals. Images PMID:1868829

  9. Relationships Between Metabolic Rate, Muscle Electromyograms and Swim Performance of Adult Chinook Salmon

    SciTech Connect

    Geist, David R.; Brown, Richard S.; Cullinan, Valerie I.; Mesa, Matthew G.; VanderKooi, S P.; McKinstry, Craig A.

    2003-10-01

    In 2000 Pacific Northwest National Laboratory initiated a two-year study to investigate the metabolic rate and swimming performance and to estimate the total energy used (i.e., aerobic and anaerobic) by adult spring Chinook salmon migrating upstream through a large hydropower dam on the Columbia River. The investigation involved one year of laboratory study and one year of field study at Bonneville Dam. The objectives of the laboratory study, reported here, were to (1) measure active rates of oxygen consumption of adult spring chinook salmon at three water temperatures over a range of swimming speeds; (2) estimate the Ucrit of adult spring chinook salmon; and (3) monitor EMGs of red and white muscle in the salmon over a range of swimming speeds. Future papers will report on the results of the field study. Our results indicated that the rate of oxygen consumption and red and white muscle activity in adult spring chinook salmon were strongly correlated with swimming speed over a range of fish sizes and at three different temperatures. Active oxygen consumption increased linearly with swim speed before leveling off at speeds at or above Ucrit. This pattern was similar at each water temperature and indicated that fish were approaching their maximal aerobic oxygen consumption at higher swim speeds. Modeling showed that temperature, but not size or sex, influenced the relation between V02 and swim speed, thus a V02-swim speed model based on temperature (but independent of sex and size) should be a biologically relevant way of estimating the energy use of fish in the wild.

  10. Systemic elevation of interleukin-15 in vivo promotes apoptosis in skeletal muscles of young adult and aged rats.

    PubMed

    Pistilli, Emidio E; Alway, Stephen E

    2008-08-15

    In this study, we tested the hypothesis that systemic elevation of IL-15 would attenuate apoptosis in skeletal muscles of aged rats. IL-15 was administered to young adult (n=6) and aged (n=6) rats for 14 days. Apoptosis was quantified using an ELISA assay and verified through TUNEL staining of muscle sections. As expected, apoptosis was greater in muscles from aged control rats, compared to age-matched control. Apoptosis was also greater in the muscles from young adult and aged rats treated with IL-15. These increases in apoptosis were associated with decreases in muscle mass of IL-15 treated rats. These data do not support our initial hypothesis and suggest that systemic elevation of IL-15 promotes apoptosis in skeletal muscle. The proposed anti-apoptotic property of IL-15 may be specific to cell-type and/or the degree of muscle pathology present; however, additional research is required to more clearly decipher its role in skeletal muscle.

  11. Variations in cross-bridge attachment rate and tension with phosphorylation of myosin in mammalian skinned skeletal muscle fibers. Implications for twitch potentiation in intact muscle

    PubMed Central

    1989-01-01

    The Ca2+ sensitivities of the rate constant of tension redevelopment (ktr; Brenner, B., and E. Eisenberg. 1986. Proceedings of the National Academy of Sciences. 83:3542-3546) and isometric force during steady- state activation were examined as functions of myosin light chain 2 (LC2) phosphorylation in skinned single fibers from rabbit and rat fast- twitch skeletal muscles. To measure ktr the fiber was activated with Ca2+ and steady isometric tension was allowed to develop; subsequently, the fiber was rapidly (less than 1 ms) released to a shorter length and then reextended by approximately 200 nm per half sarcomere. This maneuver resulted in the complete dissociation of cross-bridges from actin, so that the subsequent redevelopment of tension was related to the rate of cross-bridge reattachment. The time course of tension redevelopment, which was recorded under sarcomere length control, was best fit by a first-order exponential equation (i.e., tension = C(1 - e- kt) to obtain the value of ktr. In control fibers, ktr increased sigmoidally with increases in [Ca2+]; maximum values of ktr were obtained at pCa 4.5 and were significantly greater in rat superficial vastus lateralis fibers (26.1 +/- 1.2 s-1 at 15 degrees C) than in rabbit psoas fibers (18.7 +/- 1.0 s-1). Phosphorylation of LC2 was accomplished by repeated Ca2+ activations (pCa 4.5) of the fibers in solutions containing 6 microM calmodulin and 0.5 microM myosin light chain kinase, a protocol that resulted in an increase in LC2 phosphorylation from approximately 10% in the control fibers to greater than 80% after treatment. After phosphorylation, ktr was unchanged at maximum or very low levels of Ca2+ activation. However, at intermediate levels of Ca2+ activation, between pCa 5.5 and 6.2, there was a significant increase in ktr such that this portion of the ktr-pCa relationship was shifted to the left. The steady-state isometric tension-pCa relationship, which in control fibers was left shifted with respect

  12. Protein Considerations for Optimising Skeletal Muscle Mass in Healthy Young and Older Adults

    PubMed Central

    Witard, Oliver C.; Wardle, Sophie L.; Macnaughton, Lindsay S.; Hodgson, Adrian B.; Tipton, Kevin D.

    2016-01-01

    Skeletal muscle is critical for human health. Protein feeding, alongside resistance exercise, is a potent stimulus for muscle protein synthesis (MPS) and is a key factor that regulates skeletal muscle mass (SMM). The main purpose of this narrative review was to evaluate the latest evidence for optimising the amino acid or protein source, dose, timing, pattern and macronutrient coingestion for increasing or preserving SMM in healthy young and healthy older adults. We used a systematic search strategy of PubMed and Web of Science to retrieve all articles related to this review objective. In summary, our findings support the notion that protein guidelines for increasing or preserving SMM are more complex than simply recommending a total daily amount of protein. Instead, multifactorial interactions between protein source, dose, timing, pattern and macronutrient coingestion, alongside exercise, influence the stimulation of MPS, and thus should be considered in the context of protein recommendations for regulating SMM. To conclude, on the basis of currently available scientific literature, protein recommendations for optimising SMM should be tailored to the population or context of interest, with consideration given to age and resting/post resistance exercise conditions. PMID:27023595

  13. Effect of an Eight-Week Ballroom Dancing Program on Muscle Architecture in Older Adults Females.

    PubMed

    Cepeda, Christina C P; Lodovico, Angélica; Fowler, Neil; Rodacki, André L F

    2015-10-01

    Aging is related to a progressive remodeling of the neuromuscular system, which includes muscle mass, strength, and power reductions. This study investigated the effect of an eight-week dance program on fascicle pennation angle, fascicle length, and thickness of the vastus lateralis (VL), tibialis anterior (TA), biceps femoris (BF), and gastrocnemius medialis (GM) muscles using ultrasound images. Thirty-four healthy older women were randomly assigned to either a dancing (DG: n = 19, 69.1 ± 6.5 years, 72.5 ± 11.7 kg) or control group (CG: n = 15, 71.5 ± 7.4 years, 70.9 ± 9.3 kg). After training, the DG showed greater (p < .05) thickness for VL (16%), TA (17%), BF (19%), and GM (15%); pennation angle for VL (21%), TA (23%), BF (21%), and GM (17%); and fascicle length for VL (11%), TA (12%), BF (10%), and GM (10%). These findings suggest that dance training was effective to change the lower limb muscle architecture in older female adults.

  14. Maternal High Fat Diet Alters Skeletal Muscle Mitochondrial Catalytic Activity in Adult Male Rat Offspring

    PubMed Central

    Pileggi, Chantal A.; Hedges, Christopher P.; Segovia, Stephanie A.; Markworth, James F.; Durainayagam, Brenan R.; Gray, Clint; Zhang, Xiaoyuan D.; Barnett, Matthew P. G.; Vickers, Mark H.; Hickey, Anthony J. R.; Reynolds, Clare M.; Cameron-Smith, David

    2016-01-01

    A maternal high-fat (HF) diet during pregnancy can lead to metabolic compromise, such as insulin resistance in adult offspring. Skeletal muscle mitochondrial dysfunction is one mechanism contributing to metabolic impairments in insulin resistant states. Therefore, the present study aimed to investigate whether mitochondrial dysfunction is evident in metabolically compromised offspring born to HF-fed dams. Sprague-Dawley dams were randomly assigned to receive a purified control diet (CD; 10% kcal from fat) or a high fat diet (HFD; 45% kcal from fat) for 10 days prior to mating, throughout pregnancy and during lactation. From weaning, all male offspring received a standard chow diet and soleus muscle was collected at day 150. Expression of the mitochondrial transcription factors nuclear respiratory factor-1 (NRF1) and mitochondrial transcription factor A (mtTFA) were downregulated in HF offspring. Furthermore, genes encoding the mitochondrial electron transport system (ETS) respiratory complex subunits were suppressed in HF offspring. Moreover, protein expression of the complex I subunit, NDUFB8, was downregulated in HF offspring (36%), which was paralleled by decreased maximal catalytic linked activity of complex I and III (40%). Together, these results indicate that exposure to a maternal HF diet during development may elicit lifelong mitochondrial alterations in offspring skeletal muscle. PMID:27917127

  15. Ratio of C-Reactive Protein to Albumin Predicts Muscle Mass in Adult Patients Undergoing Hemodialysis

    PubMed Central

    Chen, Yu-Tong; Wu, Pei-Yu; Chen, Hsi-Hsien; Chen, Tso-Hsiao; Hsu, Yung-Ho

    2016-01-01

    Recent studies have indicated that the ratio of C-reactive protein to albumin (CRP–Alb ratio) is associated with clinical outcomes in patients with disease. We examined the predictive value of this ratio in patients undergoing hemodialysis (HD). In this cross-sectional study, 91 eligible adult HD patients were analyzed, and the correlation between the CRP–Alb ratio and skeletal muscle mass normalized for body weight (SMM/wt; estimated using a bioelectrical impedance analyzer) was investigated. The mean age of the study participants was 54.9 ± 6.6 years (ranging from 27 to 64 years); 43 (47.2%) were men. The mean values for the SMM/wt were 39.1% ± 5.4%. The CRP–Alb ratio was found to be negatively correlated with SMM/wt (r = −0.33, P = 0.002) and creatinine (r = −0.20, P = 0.056). All the univariate significant and nonsignificant relevant covariates were selected for multivariable stepwise regression analysis. We determined that the homeostasis model assessment-estimated insulin resistance and CRP–Alb ratio were independent risk determinants for SMM/wt (βHOMA-IR = −0.18 and βCRP–Alb ratio = −3.84, adjusted R2 = 0.32). This study indicated that the CRP–Alb ratio may help clinicians in predicting muscle mass in adult patients undergoing HD. PMID:27768746

  16. The area composita of adhering junctions connecting heart muscle cells of vertebrates. VI. Different precursor structures in non-mammalian species.

    PubMed

    Pieperhoff, Sebastian; Franke, Werner W

    2008-07-01

    Recent studies on the formation and molecular organization of the mammalian heart have emphasized the architectural and functional importance of the adhering junctions (AJs), which are densely clustered in the bipolar end regions (intercalated disks, IDs) connecting the elongated cardiomyocytes of the adult heart. Moreover, we learned from genetic studies of mutated AJ proteins that desmosomal proteins, which for the most part are integral components of ID-specific composite AJs (areae compositae, AC), are essential in heart development and function. Developmental studies have shown that the bipolar concentration of cardiomyocyte AJs in IDs is a rather late process and only completed postnatally. Here we report that in the adult hearts of diverse lower vertebrates (fishes, amphibia, birds) most AJs remain separate and distinct in molecular character, representing either fasciae adhaerentes, maculae adhaerentes (desmosomes) or--less frequently--some form of AC. In the mature hearts of the amphibian and fish species examined a large proportion of the AJs connecting cardiomyocytes is not clustered in the IDs but remains located on the lateral surfaces where they appear either as puncta adhaerentia or as desmosomes. In many places, these puncta connect parallel cardiomyocytes in spectacular ladder-like regular arrays (scalae adhaerentes) correlated with--and connected by--electron-dense plaque-like material to sarcomeric Z-bands. In the avian hearts, on the other hand, most AJs are clustered in the IDs but only a small proportion of the desmosomes appears as AC, compared to the dominance of distinct fasciae adhaerentes. We conclude that the fusion and amalgamation of AJs and desmosomes to ACs is a late process both in ontogenesis and in evolution. The significance and possible functional implications of the specific junctional structures in vertebrate evolution and the class-specific requirements of architectural and molecular assembly adaptation during regeneration

  17. Mammalian sleep

    NASA Astrophysics Data System (ADS)

    Staunton, Hugh

    2005-05-01

    This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

  18. Leucine supplementation chronically improves muscle protein synthesis in older adults consuming the RDA for protein

    PubMed Central

    Casperson, Shanon L.; Sheffield-Moore, Melinda; Hewlings, Susan J.; Paddon-Jones, Douglas

    2013-01-01

    SUMMARY Background & aim Protein-energy supplementation is routinely employed to combat muscle loss. However, success is often compromised by increased satiety, poor palatability, high costs and low compliance. Methods For 2-weeks we supplemented meals of older individuals with leucine (4 g/meal; 3 meals/day; days 2–14). Metabolic studies were performed prior to (Day 1) and following (Day 15) supplementation. Leucine was not provided on metabolic study days. Venous blood and vastus lateralis muscle biopsies were obtained during a primed constant infusion of L-[ring-13C6] phenylalanine. Mixed muscle fractional synthesis rate (FSR), body composition and markers of nutrient signaling (mTOR, 4E-BP1 and p70S6K1 phosphorylation) were measured before and after a low protein/carbohydrate simulated meal. Results The meal modestly increased FSR on Day 1 (postabsorptive: 0.063 ± 0.004 vs. postprandial: 0.075 ± 0.006%/h; p = 0.03), however, two weeks of leucine supplementation increased postabsorptive FSR (p = 0.004) and the response to the meal (p = 0.01) (postabsorptive: 0.074 ± 0.007 vs. postprandial: 0.10 ± 0.007%/h). Changes in FSR were mirrored by increased phosphorylation of mTOR, 4E-BP1 and p70S6K1 (p ≤ 0.1). No change in fat free mass was observed (p > 0.05). Conclusions In older adults, leucine supplementation may improve muscle protein synthesis in response to lower protein meals. PMID:22357161

  19. Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults

    PubMed Central

    Raue, Ulrika; Trappe, Todd A.; Estrem, Shawn T.; Qian, Hui-Rong; Helvering, Leah M.; Smith, Rosamund C.

    2012-01-01

    This investigation examined the effects of acute resistance exercise (RE), progressive resistance training (PRT), and age on the human skeletal muscle Transcriptome. Two cohorts of young and old adults [study A: 24 yr, 84 yr (n = 28); study B: 25 yr, 78 yr (n = 36)] were studied. Vastus lateralis biopsies were obtained pre- and 4 h post-RE in conjunction with the 1st and 36th (last) training session as part of a 12-wk PRT program in study A, whereas biopsies were obtained in the basal untrained state in study B. Additionally, the muscle fiber type specific (MHC I and MHC IIa) Transcriptome response to RE was examined in a subset of young and old women from study A. Transcriptome profiling was performed using HG U133 Plus 2.0 Arrays. The main findings were 1) there were 661 genes affected by RE during the 1st and 36th training bout that correlated with gains in muscle size and strength with PRT (termed the Transcriptome signature of resistance exercise adaptations); 2) the RE gene response was most pronounced in fast-twitch (MHC IIa) muscle fibers and provided additional insight into the skeletal muscle biology affected by RE; 3) skeletal muscle of young adults is more responsive to RE at the gene level compared with old adults and age also affected basal level skeletal muscle gene expression. These skeletal muscle Transcriptome findings provide further insight into the molecular basis of sarcopenia and the impact of resistance exercise at the mixed muscle and fiber type specific level. PMID:22302958

  20. Voltage clamp methods for the study of membrane currents and SR Ca2+ release in adult skeletal muscle fibres

    PubMed Central

    Hernández-Ochoa, Erick O.; Schneider, Martin F.

    2012-01-01

    Skeletal muscle excitation-contraction (E-C)1 coupling is a process composed of multiple sequential stages, by which an action potential triggers sarcoplasmic reticulum (SR)2 Ca2+ release and subsequent contractile activation. The various steps in the E-C coupling process in skeletal muscle can be studied using different techniques. The simultaneous recordings of sarcolemmal electrical signals and the accompanying elevation in myoplasmic Ca2+, due to depolarization-initiated SR Ca2+ release in skeletal muscle fibres, have been useful to obtain a better understanding of muscle function. In studying the origin and mechanism of voltage dependency of E-C coupling a variety of different techniques have been used to control the voltage in adult skeletal fibres. Pioneering work in muscles isolated from amphibians or crustaceans used microelectrodes or ‘high resistance gap’ techniques to manipulate the voltage in the muscle fibres. The development of the patch clamp technique and its variant, the whole-cell clamp configuration that facilitates the manipulation of the intracellular environment, allowed the use of the voltage clamp techniques in different cell types, including skeletal muscle fibres. The aim of this article is to present an historical perspective of the voltage clamp methods used to study skeletal muscle E-C coupling as well as to describe the current status of using the whole-cell patch clamp technique in studies in which the electrical and Ca2+ signalling properties of mouse skeletal muscle membranes are being investigated. PMID:22306655

  1. Fish oil–derived n–3 PUFA therapy increases muscle mass and function in healthy older adults1

    PubMed Central

    Smith, Gordon I; Julliand, Sophie; Reeds, Dominic N; Sinacore, David R; Klein, Samuel; Mittendorfer, Bettina

    2015-01-01

    Background: Age-associated declines in muscle mass and function are major risk factors for an impaired ability to carry out activities of daily living, falls, prolonged recovery time after hospitalization, and mortality in older adults. New strategies that can slow the age-related loss of muscle mass and function are needed to help older adults maintain adequate performance status to reduce these risks and maintain independence. Objective: We evaluated the efficacy of fish oil–derived n–3 (ω-3) PUFA therapy to slow the age-associated loss of muscle mass and function. Design: Sixty healthy 60–85-y-old men and women were randomly assigned to receive n–3 PUFA (n = 40) or corn oil (n = 20) therapy for 6 mo. Thigh muscle volume, handgrip strength, one-repetition maximum (1-RM) lower- and upper-body strength, and average power during isokinetic leg exercises were evaluated before and after treatment. Results: Forty-four subjects completed the study [29 subjects (73%) in the n–3 PUFA group; 15 subjects (75%) in the control group]. Compared with the control group, 6 mo of n–3 PUFA therapy increased thigh muscle volume (3.6%; 95% CI: 0.2%, 7.0%), handgrip strength (2.3 kg; 95% CI: 0.8, 3.7 kg), and 1-RM muscle strength (4.0%; 95% CI: 0.8%, 7.3%) (all P < 0.05) and tended to increase average isokinetic power (5.6%; 95% CI: −0.6%, 11.7%; P = 0.075). Conclusion: Fish oil–derived n–3 PUFA therapy slows the normal decline in muscle mass and function in older adults and should be considered a therapeutic approach for preventing sarcopenia and maintaining physical independence in older adults. This study was registered at clinicaltrials.gov as NCT01308957. PMID:25994567

  2. Constitutive Expression of Yes-Associated Protein (Yap) in Adult Skeletal Muscle Fibres Induces Muscle Atrophy and Myopathy

    PubMed Central

    Judson, Robert N.; Gray, Stuart R.; Walker, Claire; Carroll, Andrew M.; Itzstein, Cecile; Lionikas, Arimantas; Zammit, Peter S.; De Bari, Cosimo; Wackerhage, Henning

    2013-01-01

    The aim of this study was to investigate the function of the Hippo pathway member Yes-associated protein (Yap, gene name Yap1) in skeletal muscle fibres in vivo. Specifically we bred an inducible, skeletal muscle fibre-specific knock-in mouse model (MCK-tTA-hYAP1 S127A) to test whether the over expression of constitutively active Yap (hYAP1 S127A) is sufficient to drive muscle hypertrophy or stimulate changes in fibre type composition. Unexpectedly, after 5–7 weeks of constitutive hYAP1 S127A over expression, mice suddenly and rapidly lost 20–25% body weight and suffered from gait impairments and kyphosis. Skeletal muscles atrophied by 34–40% and the muscle fibre cross sectional area decreased by ≈40% when compared to control mice. Histological analysis revealed evidence of skeletal muscle degeneration and regeneration, necrotic fibres and a NADH-TR staining resembling centronuclear myopathy. In agreement with the histology, mRNA expression of markers of regenerative myogenesis (embryonic myosin heavy chain, Myf5, myogenin, Pax7) and muscle protein degradation (atrogin-1, MuRF1) were significantly elevated in muscles from transgenic mice versus control. No significant changes in fibre type composition were detected using ATPase staining. The phenotype was largely reversible, as a cessation of hYAP1 S127A expression rescued body and muscle weight, restored muscle morphology and prevented further pathological progression. To conclude, high Yap activity in muscle fibres does not induce fibre hypertrophy nor fibre type changes but instead results in a reversible atrophy and deterioration. PMID:23544078

  3. Mild eccentric exercise increases Hsp72 content in skeletal muscles from adult and late middle-aged rats.

    PubMed

    Lewis, Evan J H; Ramsook, Andrew H; Locke, Marius; Amara, Catherine E

    2013-09-01

    The loss of muscle mass with age or sarcopenia contributes to increased morbidity and mortality. Thus, preventing muscle loss with age is important for maintaining health. Hsp72, the inducible member of the Hsp70 family, is known to provide protection to skeletal muscle and can be increased by exercise. However, ability to increase Hsp72 by exercise is intensity-dependent and appears to diminish with advanced age. Thus, other exercise modalities capable of increasing HSP content and potentially preventing the age related loss of muscle need to be explored. The purpose of this study was to determine if the stress from one bout of mild eccentric exercise was sufficient to elicit an increase in Hsp72 content in the vastus intermedius (VI) and white gastrocnemius (WG) muscles, and if the Hsp72 response differed between adult and late middle-aged rats. To do this, 30 adult (6 months) and late middle-aged (24 months) F344BN rats were randomly divided into three groups (n = 6/group): control (C), level exercise (16 m x min(-1)) and eccentric exercise (16 m x min(-1), 16 degree decline). Exercised animals were sacrificed immediately post-exercise or after 48 hours. Hematoxylin and Eosin staining was used to assess muscle damage, while Western Blotting was used to measure muscle Hsp72 content. A nested ANOVA with Tukey post hoc analysis was performed to determine significant difference (p < 0.05) between groups. Hsp72 content was increased in the VI for both adult and late middle-aged rats 48 hours after eccentric exercise when compared to level and control groups but no differences between age groups was observed. Hsp72 was not detected in the WG following any type of exercise. In conclusion, mild eccentric exercise can increase Hsp72 content in the rat VI muscle and this response is maintained into late middle-age.

  4. Effect of an Exercise Protocol on Pelvic Muscle Resting Pressure in Healthy Adult Women.

    DTIC Science & Technology

    1992-01-01

    Anatomy and Physiology............. 7 Causes of Pelvic Muscle Dysfunction .............. 9 Pelvic Muscle Assessment Methods................. 12...muscle dysfunction , (c) pelvic muscle assessment methods, (d) exercise and the pelvic muscles, (e) principles of exercise training, and (f) application of...extends from the pubic bone to the coccyx, with gaps for the passage of the urethra, vagina, and anus. The iliococcygeus originates from a fascial

  5. Efficient single muscle fiber isolation from alcohol-fixed adult muscle following β-galactosidase staining for satellite cell detection.

    PubMed

    Verma, Mayank; Asakura, Atsushi

    2011-01-01

    Staining for β-galactosidase activity for whole tissues, sections, and cells is a common method to detect expression of β-galactosidase reporter transgene as well as senescence-dependent β-galactosidase activity. Choice of fixatives is a critical step for detection of β-galactosidase activity, subsequent immunostaining, and enzymatic digestion of tissue to dissociate cells. In this report, the authors examined several aldehyde and alcohol fixatives in mouse skeletal muscle tissues for their efficiency at improving detection of β-galactosidase activity as well as detection by immunostaining. In addition, fixatives were also analyzed for their efficiency for collagenase digestion to isolate single muscle fibers on postfixed β-galactosidase-stained whole skeletal muscle tissues. The results show that fixing cells with isopropanol yields the greatest reliability and intensity in both β-galactosidase staining as well as double staining for β-galactosidase activity and antibodies. In addition, isopropanol and ethanol, but not glutaraldehyde or paraformaldehyde, allow for the isolation of single muscle fibers from the diaphragm and tibialis anterior muscles following postfixed β-galactosidase staining. Using this method, it is possible to identify the amount of cells that occupy the satellite cell compartment in single muscle fibers prepared from any muscle tissues, including tibialis anterior muscle and diaphragm.

  6. Pitx genes are redeployed in adult myogenesis where they can act to promote myogenic differentiation in muscle satellite cells.

    PubMed

    Knopp, Paul; Figeac, Nicolas; Fortier, Mathieu; Moyle, Louise; Zammit, Peter S

    2013-05-01

    Skeletal muscle retains a resident stem cell population called satellite cells. Although mitotically quiescent in mature muscle, satellite cells can be activated to produce myoblast progeny to generate myonuclei for skeletal muscle homoeostasis, hypertrophy and repair. Regulation of satellite cell function in adult requires redeployment of many of the regulatory networks fundamental to developmental myogenesis. Involved in such control of muscle stem cell fate in embryos are members of the Pitx gene family of bicoid-class homeodomain proteins. Here, we investigated the expression and function of all three Pitx genes in muscle satellite cells of adult mice. Endogenous Pitx1 was undetectable, whilst Pitx2a, Pitx2b and Pitx2c were at low levels in proliferating satellite cells, but increased during the early stages of myogenic differentiation. By contrast, proliferating satellite cells expressed robust amounts of Pitx3, with levels then decreasing as cells differentiated, although Pitx3 remained expressed in unfused myoblasts. To examine the role of Pitx genes in satellite cell function, retroviral-mediated expression of Pitx1, all Pitx2 isoforms or Pitx3, was used. Constitutive expression of any Pitx isoform suppressed satellite cell proliferation, with the cells undergoing enhanced myogenic differentiation. Conversely, myogenic differentiation into multinucleated myotubes was decreased when Pitx2 or Pitx3 levels were reduced using siRNA. Together, our results show that Pitx genes play a role in regulating satellite cell function during myogenesis in adult.

  7. Clustering of strength, physical function, muscle and adiposity characteristics and risk of disability in older adults

    PubMed Central

    Cawthon, Peggy M.; Fox, Kathleen M.; Gandra, Shravanthi. R.; Delmonico, Matthew J.; Chiou, Chiun-Fang; Anthony, Mary S.; Caserotti, Paolo; Kritchevsky, Stephen B.; Newman, Anne B.; Goodpaster, Bret H.; Satterfield, Suzanne; Cummings, Steven R.; Harris, Tamara B.

    2011-01-01

    Objectives Strength, physical performance, adiposity and lean mass may be independent risk factors for disability in older adults. The aim of this study was to empirically identify groupings of these interrelated measures and test how such groupings may relate to disability risk. Design Prospective Health, Aging and Body Composition Study (Health ABC) Setting Two US clinical centers Participants 1,263 women and 1,221 men Measurements Weight, strength (knee extension, grip); walking speed; chair stands; dual x-ray absorptiometry (fat and lean mass for total body, arm, and leg; percent fat); and thigh computed tomography scans (muscle area, muscle density). Analyses were stratified by sex. Factor analysis reduced these variables into a smaller number of components, and proportional hazards models assessed risk of major disability for the components identified. Results In both sexes, factor analysis reduced the 14 individual variables into three components that explained 76–77% of the data variance: Factor 1, an adiposity component, with strong loading by fat mass, weight and muscle density; Factor 2, a strength/lean body size component with strong loading by lean mass, weight and strength; Factor 3, a physical performance component with positive loading by walking speed and chair stands performance. Factor 1 (adiposity) and Factor 3 (performance), but not Factor 2 (strength/lean body size), were associated with disability over 6.1 (± 2.6 SD) years. Conclusion Adiposity and physical performance constructs, but not the strength/lean body size construct, were associated with disability risk, suggesting that adiposity and performance should be considered as risk factors for disability. PMID:21568948

  8. A subpopulation of adult skeletal muscle stem cells retains all template DNA strands after cell division.

    PubMed

    Rocheteau, Pierre; Gayraud-Morel, Barbara; Siegl-Cachedenier, Irene; Blasco, Maria A; Tajbakhsh, Shahragim

    2012-01-20

    Satellite cells are adult skeletal muscle stem cells that are quiescent and constitute a poorly defined heterogeneous population. Using transgenic Tg:Pax7-nGFP mice, we show that Pax7-nGFP(Hi) cells are less primed for commitment and have a lower metabolic status and delayed first mitosis compared to Pax7-nGFP(Lo) cells. Pax7-nGFP(Hi) can give rise to Pax7-nGFP(Lo) cells after serial transplantations. Proliferating Pax7-nGFP(Hi) cells exhibit lower metabolic activity, and the majority performs asymmetric DNA segregation during cell division, wherein daughter cells retaining template DNA strands express stem cell markers. Using chromosome orientation-fluorescence in situ hybridization, we demonstrate that all chromatids segregate asymmetrically, whereas Pax7-nGFP(Lo) cells perform random DNA segregation. Therefore, quiescent Pax7-nGFP(Hi) cells represent a reversible dormant stem cell state, and during muscle regeneration, Pax7-nGFP(Hi) cells generate distinct daughter cell fates by asymmetrically segregating template DNA strands to the stem cell. These findings provide major insights into the biology of stem cells that segregate DNA asymmetrically.

  9. Relationships between metabolic rate, muscle electromyograms and swim performance of adult chinook salmon

    USGS Publications Warehouse

    Geist, D.R.; Brown, R.S.; Cullinan, V.I.; Mesa, M.G.; VanderKooi, S.P.; McKinstry, C.A.

    2003-01-01

    Oxygen consumption rates of adult spring chinook salmon Oncorhynchus tshawytscha increased with swim speed and, depending on temperature and fish mass, ranged from 609 mg O2 h-1 at 30 cm s-1 (c. 0.5 BLs-1) to 3347 mg O2 h-1 at 170 cm s -1 (c. 2.3 BLs-1). Corrected for fish mass, these values ranged from 122 to 670 mg O2 kg-1 h-1, and were similar to other Oncorhynchus species. At all temperatures (8, 12.5 and 17??C), maximum oxygen consumption values levelled off and slightly declined with increasing swim speed >170 cm s-1, and a third-order polynomial regression model fitted the data best. The upper critical swim speed (Ucrit) of fish tested at two laboratories averaged 155 cm s -1 (2.1 BLs-1), but Ucrit of fish tested at the Pacific Northwest National Laboratory were significantly higher (mean 165 cm s-1) than those from fish tested at the Columbia River Research Laboratory (mean 140 cm s-1). Swim trials using fish that had electromyogram (EMG) transmitters implanted in them suggested that at a swim speed of c. 135 cm s-1, red muscle EMG pulse rates slowed and white muscle EMG pulse rates increased. Although there was significant variation between individual fish, this swim speed was c. 80% of the Ucrit for the fish used in the EMG trials (mean Ucrit 168.2 cm s-1). Bioenergetic modelling of the upstream migration of adult chinook salmon should consider incorporating an anaerobic fraction of the energy budget when swim speeds are ???80% of the Ucrit. ?? 2003 The Fisheries Society of the British Isles.

  10. Effects of Vibration Training and Detraining on Balance and Muscle Strength in Older Adults

    PubMed Central

    Marín, Pedro J.; Martín-López, Aurora; Vicente-Campos, Davinia; Angulo-Carrere, MT; García-Pastor, Teresa; Garatachea, Nuria; Chicharro, José L.

    2011-01-01

    The purpose of this study was to analyze the effects of 2 days/week versus 4 days/week of Whole Body Vibration (WBV) during eight weeks of WBV training on health-related quality of life (SF-36), balance and lower body strength, as well as short-term detraining (3 weeks) on balance and lower body strength among older adults. Thirty-four older adults were randomly assigned to a control group (Control; n = 11) or to one of the vibration training groups: WBV 2 days/week (WBV_2d; n = 11) or WBV 4 days/week (WBV_4d; n = 12). The WBV groups exercised for 8 weeks, following 3 weeks of detraining. Lower body strength increased significantly (p < 0.05) for both groups, WBV_2d and WBV_4d, after 8-week training. A significant reduction in strength was observed following 3 weeks of detraining only in WBV_2d group (p < 0.05). All variables of the SF-36 and the balance test did not change after intervention in any group. 2 days/week and 4 days/week of WBV during 8 weeks showed the same improvements on muscle strength. 3 weeks of detraining did not reverse the gains in strength made during 32 sessions of WBV. Key points 2 days and 4 days per week of WBV training during 8 weeks showed the same improvements on muscle strength. 3 weeks of detraining did not reverse the gains in strength made during 32 sessions of WBV exercise. 3 weeks of detraining did reverse the gains in strength made during 16 sessions of WBV exercise. PMID:24150633

  11. Accelerometer‐determined physical activity, muscle mass, and leg strength in community‐dwelling older adults

    PubMed Central

    Foong, Yi Chao; Chherawala, Nabil; Aitken, Dawn; Winzenberg, Tania; Jones, Graeme

    2015-01-01

    Abstract Introduction The aim of this study was to describe the relationship between accelerometer‐determined physical activity (PA), muscle mass, and lower‐limb strength in community‐dwelling older adults. Methods Six hundred thirty‐six community‐dwelling older adults (66 ± 7 years) were studied. Muscle mass was measured using dual‐energy x‐ray absorptiometry, whilst lower limb strength was measured via dynamometry. We measured minutes/day spent in sedentary, light, moderate, and vigorous intensity activity using Actigraph GT1M accelerometers. Results Participants spent a median of 583(Interquartile ratio (IQR) 522–646), 225(176–271), 27(12–45) and 0(0–0) min in sedentary, light, moderate, and vigorous activity, respectively. PA intensity was positively associated with both lean mass percentage and lower limb strength in a dose–response fashion. Sedentary activity was negatively associated with lean mass percentage, but not lower‐limb strength. There was a positive association between PA and appendicular lean mass in men only. There was an interaction between age and activity; as age increased, the magnitude of the association of PA with lean mass percentage decreased. Those who adhered to the Australian Department of Health PA guidelines (moderate/vigorous PA >/=150 min/week) had greater lean mass percentage, appendicular lean mass, and lower limb strength. Conclusions Using accelerometer technology, both the amount and intensity of accelerometer‐determined PA had an independent, dose–response relationship with lean mass percentage and lower limb strength, with the largest effect for vigorous activity. Time spent in sedentary activity was negatively associated with lean mass percentage, but was not associated with lower limb strength. The magnitude of the association between PA and lean mass percentage decreased with age, suggesting that PA programmes may need to be modified with increasing age. PMID:27239404

  12. Skeletal Muscle Mitochondrial Energetics Are Associated With Maximal Aerobic Capacity and Walking Speed in Older Adults

    PubMed Central

    2013-01-01

    Background. Lower ambulatory performance with aging may be related to a reduced oxidative capacity within skeletal muscle. This study examined the associations between skeletal muscle mitochondrial capacity and efficiency with walking performance in a group of older adults. Methods. Thirty-seven older adults (mean age 78 years; 21 men and 16 women) completed an aerobic capacity (VO2 peak) test and measurement of preferred walking speed over 400 m. Maximal coupled (State 3; St3) mitochondrial respiration was determined by high-resolution respirometry in saponin-permeabilized myofibers obtained from percutanous biopsies of vastus lateralis (n = 22). Maximal phosphorylation capacity (ATPmax) of vastus lateralis was determined in vivo by 31P magnetic resonance spectroscopy (n = 30). Quadriceps contractile volume was determined by magnetic resonance imaging. Mitochondrial efficiency (max ATP production/max O2 consumption) was characterized using ATPmax per St3 respiration (ATPmax/St3). Results. In vitro St3 respiration was significantly correlated with in vivo ATPmax (r 2 = .47, p = .004). Total oxidative capacity of the quadriceps (St3*quadriceps contractile volume) was a determinant of VO2 peak (r 2 = .33, p = .006). ATPmax (r 2 = .158, p = .03) and VO2 peak (r 2 = .475, p < .0001) were correlated with preferred walking speed. Inclusion of both ATPmax/St3 and VO2 peak in a multiple linear regression model improved the prediction of preferred walking speed (r 2 = .647, p < .0001), suggesting that mitochondrial efficiency is an important determinant for preferred walking speed. Conclusions. Lower mitochondrial capacity and efficiency were both associated with slower walking speed within a group of older participants with a wide range of function. In addition to aerobic capacity, lower mitochondrial capacity and efficiency likely play roles in slowing gait speed with age. PMID:23051977

  13. Range of motion, muscle length, and balance performance in older adults with normal, pronated, and supinated feet

    PubMed Central

    Justine, Maria; Ruzali, Dhiya; Hazidin, Ezzaty; Said, Aisyah; Bukry, Saiful Adli; Manaf, Haidzir

    2016-01-01

    [Purpose] To compare the lower limb joint range of motion and muscle length between different types of foot posture, and determine the correlation of range of motion and muscle length with balance performance. [Subjects and Methods] Ninety individuals (age, 65.2±4.6 years) were assessed using the Foot Posture Index to determine their type of foot (Normal [0 to +5], pronated [+6 to +9], and supinated [−1 to −4]; n=30 per group). The range of motion (goniometer), muscle length (goniometer and tape measure), and balance performance (functional reach test and four square step test) were measured for each participant. Data were analyzed using the Kruskal-Wallis test and Spearman’s rank-order correlation. [Results] No significant differences were found in range of motion, muscle length, and balance performance among different types of foot posture, except for right and left ankle dorsiflexion range of motion. Balance performance was significantly correlated with selected muscle length and range of motion, especially in the supinated foot. [Conclusion] Range of motion and muscle length of the lower limb may be associated with balance performance in older adults with foot deformities. These findings may guide physiotherapists in choosing intervention based on specific assessments for older adults with foot deformity. PMID:27134384

  14. Increases in muscle strength and balance using a resistance training program administered via a telecommunications system in older adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Resistance training programs have been found to improve muscle strength, physical function, and depressive symptoms in middle-aged and older adults. These programs have typically been provided in clinical facilities, health clubs, and senior centers, which may be inconvenient and/or cos...

  15. Relationships between Muscle Architecture of Rectus Femoris and Functional Parameters of Knee Motion in Adults with Down Syndrome

    PubMed Central

    Micale, Marco; Cioni, Matteo

    2016-01-01

    This study was designed to measure in vivo muscle architecture of the rectus femoris in adults with Down syndrome, testing possible relationships with functional parameters of the knee motion. Ten adults with Down syndrome and ten typically developed participated in the study. Pennation angle and thickness of the rectus femoris and subcutaneous layer of the thigh were measured via ultrasound imaging. Knee kinematics and electromyographic activity of the rectus femoris were recorded during free leg dropping. Muscle thickness was reduced and subcutaneous layer was thicker in persons with Down syndrome with respect to typically developed adults, but there were no differences in the pennation angle. The area of the rectus femoris EMG activity during the leg flexion was greater in Down syndrome with respect to typically developed adults. The leg movement velocity was lower in Down people than in controls, but the knee excursion was similar between the groups. Functional parameters correlated with pennation angle in the persons with Down syndrome and with muscle thickness in typically developed persons. The description of muscle architecture and the relationships between morphological and functional parameters may provide insights on the limits and the opportunities to overcome the inherent biomechanical instability in Down syndrome. PMID:27896273

  16. Relationships between Muscle Architecture of Rectus Femoris and Functional Parameters of Knee Motion in Adults with Down Syndrome.

    PubMed

    Valle, Maria Stella; Casabona, Antonino; Micale, Marco; Cioni, Matteo

    2016-01-01

    This study was designed to measure in vivo muscle architecture of the rectus femoris in adults with Down syndrome, testing possible relationships with functional parameters of the knee motion. Ten adults with Down syndrome and ten typically developed participated in the study. Pennation angle and thickness of the rectus femoris and subcutaneous layer of the thigh were measured via ultrasound imaging. Knee kinematics and electromyographic activity of the rectus femoris were recorded during free leg dropping. Muscle thickness was reduced and subcutaneous layer was thicker in persons with Down syndrome with respect to typically developed adults, but there were no differences in the pennation angle. The area of the rectus femoris EMG activity during the leg flexion was greater in Down syndrome with respect to typically developed adults. The leg movement velocity was lower in Down people than in controls, but the knee excursion was similar between the groups. Functional parameters correlated with pennation angle in the persons with Down syndrome and with muscle thickness in typically developed persons. The description of muscle architecture and the relationships between morphological and functional parameters may provide insights on the limits and the opportunities to overcome the inherent biomechanical instability in Down syndrome.

  17. Stereoselective effects of mexiletine enantiomers on sodium currents and excitability characteristics of adult skeletal muscle fibers.

    PubMed

    De Luca, A; Natuzzi, F; Lentini, G; Franchini, C; Tortorella, V; Conte Camerino, D

    1995-12-01

    drugs on adult skeletal muscle sodium channels. The constant eudismic ratios between the enantiomers during both tonic and use-dependent block suggest that the increase in the apparent affinity of the receptor during state-dependent conformational changes of the channel does not enhance its stereospecificity. The decrease in effective concentration upon high frequency stimulation supports the potential usefulness of low doses of R-(-) mexiletine in the treatment of the abnormal hyperexcitability of the myotonic muscles, with a likely reduction of unwanted side effects.

  18. Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability

    PubMed Central

    Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

    2015-01-01

    Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability. PMID:26251896

  19. Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability.

    PubMed

    Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

    2015-08-05

    Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability.

  20. Trunk Muscle Characteristics of the Multifidi, Erector Spinae, Psoas, and Quadratus Lumborum in Older Adults With and Without Chronic Low Back Pain.

    PubMed

    Sions, J Megan; Elliott, James M; Pohlig, Ryan T; Hicks, Gregory E

    2017-03-01

    Study Design Cross-sectional study. Objective To determine whether there are differences in trunk muscle characteristics between older adults with and without chronic low back pain (LBP), while controlling for age, sex, and body mass index. Background Muscle support for the trunk is provided by the multifidi, erector spinae, psoas, and quadratus lumborum. Trunk muscle characteristics may be altered with aging and/or chronic LBP. To date, most trunk muscle research has been conducted among younger adults. Given age-related muscle changes, such as reduced size and increased intramuscular fat, studies are needed in older adults, including those comparing older adults with and without LBP. Methods One hundred two older adults with (n = 53) and without (n = 49) chronic LBP were included. Cross-sectional area (CSA) measurements were taken by tracing inside the fascial borders on magnetic resonance images. Pixel intensity summaries were obtained to compute muscle-to-fat indices and relative muscle CSA, that is, CSA void of fat. Right/left averages for levels L2 through L5 were determined. Mixed-design analyses of covariance were used to test for differences between groups, based on LBP presence and sex, across levels (P≤.05). Results Older adults with LBP had a greater average multifidus muscle-to-fat index (0.51 versus 0.49) and smaller average erector spinae relative muscle CSA (8.56 cm(2) versus 9.26 cm(2)) when compared to control participants without LBP. No interactions between LBP status and average muscle characteristics were found for the psoas or quadratus lumborum (P>.05). Conclusion Up to 54% of older adult trunk muscle CSA may be fat. Women have smaller muscles and greater intramuscular fat (at lower spinal levels) than men. J Orthop Sports Phys Ther 2017;47(3):173-179. Epub 3 Feb 2017. doi:10.2519/jospt.2017.7002.

  1. Effect of very low-intensity resistance training with slow movement on muscle size and strength in healthy older adults.

    PubMed

    Watanabe, Yuya; Madarame, Haruhiko; Ogasawara, Riki; Nakazato, Koichi; Ishii, Naokata

    2014-11-01

    We previously reported that low-intensity [50% of one repetition maximum (1RM)] resistance training with slow movement and tonic force generation (LST) causes muscle hypertrophy and strength gain in older participants. The aim of this study was to determine whether resistance training with slow movement and much more reduced intensity (30%1RM) increases muscle size and strength in older adults. Eighteen participants (60-77 years) were randomly assigned to two groups. One group performed very low-intensity (30% 1RM) knee extension exercise with continuous muscle contraction (LST: 3-s eccentric, 3-s concentric, and 1-s isometric actions with no rest between each repetition) twice a week for 12 weeks. The other group underwent intermitted muscle contraction (CON: 1-s concentric and 1-s eccentric actions with 1-s rest between each repetition) for the same time period. The 1RM, isometric and isokinetic strengths, and cross-sectional image of the mid-thigh obtained by magnetic resonance imaging were examined before and after the intervention. LST significantly increased the cross-sectional area of the quadriceps muscle (5.0%, P<0.001) and isometric and isokinetic knee extension strengths (P<0.05). CON failed to increase muscle size (1.1%, P = 0.12), but significantly improved its strength (P<0.05). These results indicate that even if the intensity is as low as 30% 1RM, LST can increase muscle size and strength in healthy older adults. The large total contraction time may be related to muscle hypertrophy and strength gain. LST would be useful for preventing sarcopenia in older individuals.

  2. Effect of weight loss on the rate of muscle protein synthesis during fasted and fed conditions in obese older adults.

    PubMed

    Villareal, Dennis T; Smith, Gordon I; Shah, Krupa; Mittendorfer, Bettina

    2012-09-01

    Although weight loss ameliorates many of the metabolic abnormalities associated with obesity, there has been reluctance to prescribe weight loss in obese, older individuals because of the fear that it will cause debilitating loss of muscle mass and impair physical function. To gain insight into the mechanisms responsible for the weight loss-induced changes in muscle mass, we measured the rate of muscle protein synthesis (by using stable isotope labeled tracer methodology) during basal, postabsorptive conditions and during mixed meal ingestion in eight obese, older adults: (i) before weight loss therapy, (ii) ~3 months after starting the weight loss intervention (i.e., during the active weight loss phase), when subjects had lost ~7% of their initial body weight, and (iii) after they had lost ~10% of their body weight and maintained this new body weight for ~6 months (~12 months after starting the weight loss intervention). The basal muscle protein fractional synthesis rate (FSR) was not affected by weight loss. Mixed meal ingestion stimulated the rate of muscle protein synthesis, and the anabolic response (i.e., increase in the protein synthesis rate above basal values) was greater (P < 0.05) during negative energy balance and active weight loss at 3 months (0.033 ± 0.012%·per hour, mean ± s.e.m.) than during weight maintenance before and at 12 months of weight loss therapy (0.003 ± 0.003 and 0.008 ± 0.012%·per hour, respectively). We conclude that during dietary calorie restriction and weight loss in older adults, the rate of muscle protein synthesis is not impaired. Thus, the loss of muscle mass must be mediated predominately by adverse effects of dietary calorie restriction on muscle proteolysis.

  3. Aural Acoustic Stapedius-Muscle Reflex Threshold Procedures to Test Human Infants and Adults.

    PubMed

    Keefe, Douglas H; Feeney, M Patrick; Hunter, Lisa L; Fitzpatrick, Denis F

    2017-02-01

    Power-based procedures are described to measure acoustic stapedius-muscle reflex threshold and supra-threshold responses in human adult and infant ears at frequencies from 0.2 to 8 kHz. The stimulus set included five clicks in which four pulsed activators were placed between each pair of clicks, with each stimulus set separated from the next by 0.79 s to allow for reflex decay. Each click response was used to detect the presence of reflex effects across frequency that were elicited by a pulsed broadband-noise or tonal activator in the ipsilateral or contralateral test ear. Acoustic reflex shifts were quantified in terms of the difference in absorbed sound power between the initial baseline click and the later four clicks in each set. Acoustic reflex shifts were measured over a 40-dB range of pulsed activators, and the acoustic reflex threshold was objectively calculated using a maximum 10 likelihood procedure. To illustrate the principles underlying these new reflex tests, reflex shifts in absorbed sound power and absorbance are presented for data acquired in an adult ear with normal hearing and in two infant ears in the initial and follow-up newborn hearing screening exams, one with normal hearing and the other with a conductive hearing loss. The use of absorbed sound power was helpful in classifying an acoustic reflex shift as present or absent. The resulting reflex tests are in use in a large study of wideband clinical diagnosis and monitoring of middle-ear and cochlear function in infant and adult ears.

  4. Enhanced Myogenesis in adult skeletal muscle by transgenic expression of Myostatin Propeptide

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Skeletal muscle growth and maintenance are essential for human health. One of the muscle regulatory genes, namely myostatin, a member of transforming growth factor-ß, plays a dominant role in the genetic control of muscle mass. Transgenic expression of myostatin propeptide in skeletal muscle showed ...

  5. Botulinum toxin in masticatory muscles: short- and long-term effects on muscle, bone, and craniofacial function in adult rabbits.

    PubMed

    Rafferty, Katherine L; Liu, Zi Jun; Ye, Wenmin; Navarrete, Alfonso L; Nguyen, Thao Tuong; Salamati, Atriya; Herring, Susan W

    2012-03-01

    Paralysis of the masticatory muscles using botulinum toxin (BTX) is a common treatment for cosmetic reduction of the masseters as well as for conditions involving muscle spasm and pain. The effects of this treatment on mastication have not been evaluated, and claims that the treatment unloads the jaw joint and mandible have not been validated. If BTX treatment does decrease mandibular loading, osteopenia might ensue as an adverse result. Rabbits received a single dose of BTX or saline into one randomly chosen masseter muscle and were followed for 4 or 12 weeks. Masticatory muscle activity was assessed weekly, and incisor bite force elicited by stimulation of each masseter was measured periodically. At the endpoint, strain gages were installed on the neck of the mandibular condyle and on the molar area of the mandible for in vivo bone strain recording during mastication and muscle stimulation. After termination, muscles were weighed and mandibular segments were scanned with micro CT. BTX paralysis of one masseter did not alter chewing side or rate, in part because of compensation by the medial pterygoid muscle. Masseter-induced bite force was dramatically decreased. Analysis of bone strain data suggested that at 4 weeks, the mandibular condyle of the BTX-injected side was underloaded, as were both sides of the molar area. Bone quantity and quality were severely decreased specifically at these underloaded locations, especially the injection-side condylar head. At 12 weeks, most functional parameters were near their pre-injection levels, but the injected masseter still exhibited atrophy and percent bone area was still low in the condylar head. In conclusion, although the performance of mastication was only minimally harmed by BTX paralysis of the masseter, the resulting underloading was sufficient to cause notable and persistent bone loss, particularly at the temporomandibular joint.

  6. Children and adults minimise activated muscle volume by selecting gait parameters that balance gross mechanical power and work demands

    PubMed Central

    Hubel, Tatjana Y.; Usherwood, James R.

    2015-01-01

    ABSTRACT Terrestrial locomotion on legs is energetically expensive. Compared with cycling, or with locomotion in swimming or flying animals, walking and running are highly uneconomical. Legged gaits that minimise mechanical work have previously been identified and broadly match walking and running at appropriate speeds. Furthermore, the ‘cost of muscle force’ approaches are effective in relating locomotion kinetics to metabolic cost. However, few accounts have been made for why animals deviate from either work-minimising or muscle-force-minimising strategies. Also, there is no current mechanistic account for the scaling of locomotion kinetics with animal size and speed. Here, we report measurements of ground reaction forces in walking children and adult humans, and their stance durations during running. We find that many aspects of gait kinetics and kinematics scale with speed and size in a manner that is consistent with minimising muscle activation required for the more demanding between mechanical work and power: spreading the duration of muscle action reduces activation requirements for power, at the cost of greater work demands. Mechanical work is relatively more demanding for larger bipeds – adult humans – accounting for their symmetrical M-shaped vertical force traces in walking, and relatively brief stance durations in running compared with smaller bipeds – children. The gaits of small children, and the greater deviation of their mechanics from work-minimising strategies, may be understood as appropriate for their scale, not merely as immature, incompletely developed and energetically sub-optimal versions of adult gaits. PMID:26400978

  7. Modulation of soleus H-reflex during shortening and lengthening muscle actions in young and older adults.

    PubMed

    Chen, Yung-Sheng; Zhou, Shi; Cartwright, Colleen

    2015-02-28

    The H-reflex is dependently modulated during isometric and anisometric muscle actions. However, the manner of the H-reflex modulation during dynamic muscle movements in relation to ageing is less stated in the literature. This study was designed to investigate the effects of ageing on soleus (SOL) H-reflex modulation during dynamic muscle actions. Twenty young (24 ± 4 years of age) and 20 older adults (73 ± 5 years of age) voluntarily participated in the study. The SOL H-reflex was measured during passive and active shortening and lengthening muscle actions in a sitting position. The older group showed a lower ratio of the maximal amplitude of H-reflex to M-wave (SOL Hmax/Mmax) during the passive lengthening than that during the passive shortening (shortening: 0.40 ± 0.22 vs. lengthening: 0.15 ± 0.10, P < 0.05), whereas the SOL Hmax/Mmax ratio of the young group was significantly higher during the shortening than that during the lengthening contractions at maximal effort (shortening: 0.51 ± 0.26 vs. lengthening: 0.37 ± 0.18, P < 0.05). These results suggested different modulations of group Ia afferent inputs to the SOL motoneurons during passive and active dynamic muscle actions between young and older adults.

  8. Active muscle regeneration following eccentric contraction-induced injury is similar between healthy young and older adults

    PubMed Central

    MacNeil, R. Gavin; Clough, Launa G.; Dirain, Marvin; Sandesara, Bhanuprasad; Pahor, Marco; Manini, Todd M.; Leeuwenburgh, Christiaan

    2013-01-01

    Repair of skeletal muscle after injury is a key aspect of maintaining proper musculoskeletal function. Studies have suggested that regenerative processes, including myogenesis and angiogenesis, are impaired during advanced age, but evidence from humans is limited. This study aimed to compare active muscle regeneration between healthy young and older adults. We evaluated changes in clinical, biochemical, and immunohistochemical indices of muscle regeneration at precisely 2 (T2) and 7 (T3) days following acute muscle injury. Men and women, aged 18-30 and ≥70 years, matched for gender and body mass index, performed 150 unilateral, eccentric contractions of the plantar flexors at 110% of one repetition maximum. Data were analyzed using analysis of covariance, adjusted for gender, habitual physical activity, and baseline level of the outcome. A total of 30 young (n = 15; 22.5 ± 3.7 yr) and older (n = 15; 75.8 ± 5.0 yr) adults completed the study. Following muscle injury, force production declined 16% and 14% in young and older adults, respectively, by T2 and in each group, returned to 93% of baseline strength by T3. Despite modest differences in the pattern of response, postinjury changes in intramuscular concentrations of myogenic growth factors and number of myonuclear (4′,6-diamidino-2-phenylindole+ and paired box 7+) cells were largely similar between groups. Likewise, postinjury changes in serum and intramuscular indices of inflammation (e.g., TNF-α and monocyte chemoattractant protein-1) and angiogenesis (e.g., VEGF and kinase insert domain receptor) did not differ significantly between groups. These findings suggest that declines in physical activity and increased co-morbidity may contribute to age-related impairments in active muscle regeneration rather than aging per se. PMID:23493365

  9. Active muscle regeneration following eccentric contraction-induced injury is similar between healthy young and older adults.

    PubMed

    Buford, Thomas W; MacNeil, R Gavin; Clough, Launa G; Dirain, Marvin; Sandesara, Bhanuprasad; Pahor, Marco; Manini, Todd M; Leeuwenburgh, Christiaan

    2014-06-01

    Repair of skeletal muscle after injury is a key aspect of maintaining proper musculoskeletal function. Studies have suggested that regenerative processes, including myogenesis and angiogenesis, are impaired during advanced age, but evidence from humans is limited. This study aimed to compare active muscle regeneration between healthy young and older adults. We evaluated changes in clinical, biochemical, and immunohistochemical indices of muscle regeneration at precisely 2 (T2) and 7 (T3) days following acute muscle injury. Men and women, aged 18-30 and ≥70 years, matched for gender and body mass index, performed 150 unilateral, eccentric contractions of the plantar flexors at 110% of one repetition maximum. Data were analyzed using analysis of covariance, adjusted for gender, habitual physical activity, and baseline level of the outcome. A total of 30 young (n = 15; 22.5 ± 3.7 yr) and older (n = 15; 75.8 ± 5.0 yr) adults completed the study. Following muscle injury, force production declined 16% and 14% in young and older adults, respectively, by T2 and in each group, returned to 93% of baseline strength by T3. Despite modest differences in the pattern of response, postinjury changes in intramuscular concentrations of myogenic growth factors and number of myonuclear (4',6-diamidino-2-phenylindole+ and paired box 7+) cells were largely similar between groups. Likewise, postinjury changes in serum and intramuscular indices of inflammation (e.g., TNF-α and monocyte chemoattractant protein-1) and angiogenesis (e.g., VEGF and kinase insert domain receptor) did not differ significantly between groups. These findings suggest that declines in physical activity and increased co-morbidity may contribute to age-related impairments in active muscle regeneration rather than aging per se.

  10. Comparing adult hippocampal neurogenesis in mammalian species and orders: influence of chronological age and life history stage.

    PubMed

    Amrein, Irmgard; Isler, Karin; Lipp, Hans-Peter

    2011-09-01

    Adult hippocampal neurogenesis is a prominent event in rodents. In species with longer life expectancies, newly born cells in the adult dentate gyrus of the hippocampal formation are less abundant or can be completely absent. Several lines of evidence indicate that the regulatory mechanisms of adult neurogenesis differ between short- and long-lived mammals. After a critical appraisal of the factors and problems associated with comparing different species, we provide a quantitative comparison derived from seven laboratory strains of mice (BALB, C57BL/6, CD1, outbred) and rats (F344, Sprague-Dawley, Wistar), six other rodent species of which four are wild-derived (wood mouse, vole, spiny mouse and guinea pig), three non-human primate species (marmoset and two macaque species) and one carnivore (red fox). Normalizing the number of proliferating cells to total granule cell number, we observe an overall exponential decline in proliferation that is chronologically equal between species and orders and independent of early developmental processes and life span. Long- and short-lived mammals differ with regard to major life history stages; at the time points of weaning, age at first reproduction and average life expectancy, long-lived primates and foxes have significantly fewer proliferating cells than rodents. Although the database for neuronal differentiation is limited, we find indications that the extent of neuronal differentiation is subject to species-specific selective adaptations. We conclude that absolute age is the critical factor regulating cell genesis in the adult hippocampus of mammals. Ontogenetic and ecological factors primarily influence the regulation of neuronal differentiation rather than the rate of cell proliferation.

  11. Leucine partially protects muscle mass and function during bed rest in middle-aged adults1,2

    PubMed Central

    English, Kirk L; Mettler, Joni A; Ellison, Jennifer B; Mamerow, Madonna M; Arentson-Lantz, Emily; Pattarini, James M; Ploutz-Snyder, Robert; Sheffield-Moore, Melinda; Paddon-Jones, Douglas

    2016-01-01

    Background: Physical inactivity triggers a rapid loss of muscle mass and function in older adults. Middle-aged adults show few phenotypic signs of aging yet may be more susceptible to inactivity than younger adults. Objective: The aim was to determine whether leucine, a stimulator of translation initiation and skeletal muscle protein synthesis (MPS), can protect skeletal muscle health during bed rest. Design: We used a randomized, double-blind, placebo-controlled trial to assess changes in skeletal MPS, cellular signaling, body composition, and skeletal muscle function in middle-aged adults (n = 19; age ± SEM: 52 ± 1 y) in response to leucine supplementation (LEU group: 0.06 g ∙ kg−1 ∙ meal−1) or an alanine control (CON group) during 14 d of bed rest. Results: Bed rest decreased postabsorptive MPS by 30% ± 9% (CON group) and by 10% ± 10% (LEU group) (main effect for time, P < 0.05), but no differences between groups with respect to pre-post changes (group × time interactions) were detected for MPS or cell signaling. Leucine protected knee extensor peak torque (CON compared with LEU group: −15% ± 2% and −7% ± 3%; group × time interaction, P < 0.05) and endurance (CON compared with LEU: −14% ± 3% and −2% ± 4%; group × time interaction, P < 0.05), prevented an increase in body fat percentage (group × time interaction, P < 0.05), and reduced whole-body lean mass loss after 7 d (CON compared with LEU: −1.5 ± 0.3 and −0.8 ± 0.3 kg; group × time interaction, P < 0.05) but not 14 d (CON compared with LEU: −1.5 ± 0.3 and −1.0 ± 0.3 kg) of bed rest. Leucine also maintained muscle quality (peak torque/kg leg lean mass) after 14 d of bed-rest inactivity (CON compared with LEU: −9% ± 2% and +1% ± 3%; group × time interaction, P < 0.05). Conclusions: Bed rest has a profoundly negative effect on muscle metabolism, mass, and function in middle-aged adults. Leucine supplementation may partially protect muscle health during relatively

  12. Idiopathic chronic fatigue in older adults is linked to impaired mitochondrial content and biogenesis signaling in skeletal muscle

    PubMed Central

    Wawrzyniak, Nicholas R.; Joseph, Anna-Maria; Levin, David G.; Gundermann, David M.; Leeuwenburgh, Christiaan; Sandesara, Bhanuprasad; Manini, Todd M.; Adhihetty, Peter J.

    2016-01-01

    Fatigue is a symptom of many diseases, but it can also manifest as a unique medical condition, such as idiopathic chronic fatigue (ICF). While the prevalence of ICF increases with age, mitochondrial content and function decline with age, which may contribute to ICF. The purpose of this study was to determine whether skeletal muscle mitochondrial dysregulation and oxidative stress is linked to ICF in older adults. Sedentary, old adults (n = 48, age 72.4 ± 5.3 years) were categorized into ICF and non-fatigued (NF) groups based on the FACIT-Fatigue questionnaire. ICF individuals had a FACIT score one standard deviation below the mean for non-anemic adults > 65 years and were excluded according to CDC diagnostic criteria for ICF. Vastus lateralis muscle biopsies were analyzed, showing reductions in mitochondrial content and suppression of mitochondrial regulatory proteins Sirt3, PGC-1α, NRF-1, and cytochrome c in ICF compared to NF. Additionally, mitochondrial morphology proteins, antioxidant enzymes, and lipid peroxidation were unchanged in ICF individuals. Our data suggests older adults with ICF have reduced skeletal muscle mitochondrial content and biogenesis signaling that cannot be accounted for by increased oxidative damage. PMID:27447862

  13. Correlation between vitamin D levels and muscle fatigue risk factors based on physical activity in healthy older adults

    PubMed Central

    Al-Eisa, Einas S; Alghadir, Ahmad H; Gabr, Sami A

    2016-01-01

    Purpose The purpose of this study was to investigate the relationship of serum vitamin D levels with physical activity, obesity, muscle fatigue biomarkers, and total antioxidant capacity (TAC) in healthy older adults. Methods A total of 85 healthy older subjects aged 64–96 years were recruited in this study. Based on estimated energy expenditure scores, the participants were classified into three groups: inactive (n=25), moderate (n=20), and physically active (n=35). Serum 25(OH)D (25-hydroxy vitamin D) levels, metabolic syndrome parameters, TAC activity, muscle fatigue biomarkers (Ca, creatine kinase, lactic acid dehydrogenase, troponin I, hydroxyproline), physical activity, body fatness, and fatigue score (visual analog scale) were estimated using immunoassay techniques and prevalidated questionnaires, respectively. Results Physical activity was estimated in 64.6% of the participants. Males showed higher physical activity (42.5%) compared to females (26.25%). Compared to participants with lower activity, significant reduction in body mass index, waist circumference, hips, fasting blood sugar, triglycerides, total cholesterol, HDL-cholesterol, and LDL-cholesterol were observed in moderate and physically active participants. Also, significant increase in the levels of serum 25(OH)D concentrations, calcium, and TAC activity along with reduction in the levels of muscle fatigue biomarkers: creatine kinase, lactic acid dehydrogenase, troponin I, hydroxyproline, and fatigue scores (visual analog scale) were reported in physically active participants compared to those of lower physical activity. In all participants, serum 25(OH)D concentrations correlated positively with Ca, TAC, physical activity scores, and negatively with body mass index, lipid profile, fatigue scores (visual analog scale), and muscle fatigue biomarkers. Stepwise regression analysis showed that serum 25(OH)D concentrations, physical activity, Ca, TAC, and demographic parameters explained

  14. Comparison of pulmonary function and back muscle strength according to the degree of spinal curvature of healthy adults.

    PubMed

    You, Jae Eung; Lee, Hye Young; Kim, Kyoung

    2015-06-01

    [Purpose] Degree of curvature on the spine is known to affect respiratory function and back muscle activation. We compared pulmonary function and back muscle strength according to the degree of curvature of the spine of healthy adults. [Subjects and Methods] Twenty-three healthy volunteers were enrolled. They were divided into two groups according to the degree of curvature of the spine: the below 2° group, and the above 2° group. The degree of curvature was assessed using the Adams forward bending test and a scoliometer. A pulmonary function test (PFT) was conducted, and back muscle strength was measured. [Results] No significant differences in PFT were found between the below 2° group and the above 2° group, in terms of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC), or peak expiratory flow (PEF). However, back muscle strength in the below 2 group was significantly higher than that of the above 2 group. [Conclusion] Our findings indicate that the degree of curvature of the spine is associated with back muscle strength in subjects who have spinal curvature within the normal range. Therefore, evaluation and treatment of back muscle strength might be helpful for preventing the progress of curvature of the spine in adolescents with potential scoliosis.

  15. Skeletal muscle myofilament adaptations to aging, disease, and disuse and their effects on whole muscle performance in older adult humans

    PubMed Central

    Miller, Mark S.; Callahan, Damien M.; Toth, Michael J.

    2014-01-01

    Skeletal muscle contractile function declines with aging, disease, and disuse. In vivo muscle contractile function depends on a variety of factors, but force, contractile velocity and power generating capacity ultimately derive from the summed contribution of single muscle fibers. The contractile performance of these fibers are, in turn, dependent upon the isoform and function of myofilament proteins they express, with myosin protein expression and its mechanical and kinetic characteristics playing a predominant role. Alterations in myofilament protein biology, therefore, may contribute to the development of functional limitations and disability in these conditions. Recent studies suggest that these conditions are associated with altered single fiber performance due to decreased expression of myofilament proteins and/or changes in myosin-actin cross-bridge interactions. Furthermore, cellular and myofilament-level adaptations are related to diminished whole muscle and whole body performance. Notably, the effect of these various conditions on myofilament and single fiber function tends to be larger in older women compared to older men, which may partially contribute to their higher rates of disability. To maintain functionality and provide the most appropriate and effective countermeasures to aging, disease, and disuse in both sexes, a more thorough understanding is needed of the contribution of myofilament adaptations to functional disability in older men and women and their contribution to tissue level function and mobility impairment. PMID:25309456

  16. A 3-D cardiac muscle construct for exploring adult marrow stem cell based myocardial regeneration.

    PubMed

    Valarmathi, Mani T; Goodwin, Richard L; Fuseler, John W; Davis, Jeffrey M; Yost, Michael J; Potts, Jay D

    2010-04-01

    Adult bone marrow stromal cells (BMSCs) are capable of differentiating into cardiomyocyte-like cells in vitro and contribute to myocardial regeneration in vivo. Consequently, BMSCs may potentially play a vital role in cardiac repair and regeneration. However, this concept has been limited by inadequate and inconsistent differentiation of BMSCs into cardiomyocytes along with poor survival and integration of neo-cardiomyocytes after implantation into ischemic myocardium. In order to overcome these barriers and to explore adult stem cell based myocardial regeneration, we have developed an in vitro model of three-dimensional (3-D) cardiac muscle using rat ventricular embryonic cardiomyocytes (ECMs) and BMSCs. When ECMs and BMSCs were seeded sequentially onto a 3-D tubular scaffold engineered from topographically aligned type I collagen-fibers and cultured in basal medium for 7, 14, 21, or 28 days, the maturation and co-differentiation into a cardiomyocyte lineage was observed. Phenotypic induction was characterized at morphological, immunological, biochemical and molecular levels. The observed expression of transcripts coding for cardiomyocyte phenotypic markers and the immunolocalization of cardiomyogenic lineage-associated proteins revealed typical expression patterns of neo-cardiomyogenesis. At the biochemical level differentiating cells exhibited appropriate metabolic activity and at the ultrastructural level myofibrillar and sarcomeric organization were indicative of an immature phenotype. Our 3-D co-culture system sustains the ECMs in vitro continuum of differentiation process and simultaneously induces the maturation and differentiation of BMSCs into cardiomyocyte-like cells. Thus, this novel 3-D co-culture system provides a useful in vitro model to investigate the functional role and interplay of developing ECMs and BMSCs during cardiomyogenic differentiation.

  17. Relationships of ultrasound measures of intrinsic foot muscle cross-sectional area and muscle volume with maximum toe flexor muscle strength and physical performance in young adults

    PubMed Central

    Abe, Takashi; Tayashiki, Kota; Nakatani, Miyuki; Watanabe, Hironori

    2016-01-01

    [Purpose] To investigate the relationships between toe flexor muscle strength with (TFS-5-toes) and without (TFS-4-toes) the contribution of the great toe, anatomical and physiological muscle cross-sectional areas (CSA) of intrinsic toe flexor muscle and physical performance were measured. [Subjects] Seventeen men (82% sports-active) and 17 women (47% sports-active), aged 20 to 35 years, volunteered. [Methods] Anatomical CSA was measured in two intrinsic toe flexor muscles (flexor digitorum brevis [FDB] and abductor hallucis) by ultrasound. Muscle volume and muscle length of the FDB were also estimated, and physiological CSA was calculated. [Results] Both TFS-5-toes and TFS-4-toes correlated positively with walking speed in men (r=0.584 and r=0.553, respectively) and women (r=0.748 and r=0.533, respectively). Physiological CSA of the FDB was significantly correlated with TFS-5-toes (r=0.748) and TFS-4-toes (r=0.573) in women. In men, physiological CSA of the FDB correlated positively with TFS-4-toes (r=0.536), but not with TFS-5-toes (r=0.333). [Conclusion] Our results indicate that physiological CSA of the FDB is moderately associated with TFS-4-toes while toe flexor strength correlates with walking performance. PMID:26957721

  18. Expression of the Otx2 homeobox gene in the developing mammalian brain: embryonic and adult expression in the pineal gland.

    PubMed

    Rath, Martin F; Muñoz, Estela; Ganguly, Surajit; Morin, Fabrice; Shi, Qiong; Klein, David C; Møller, Morten

    2006-04-01

    Otx2 is a vertebrate homeobox gene, which has been found to be essential for the development of rostral brain regions and appears to play a role in the development of retinal photoreceptor cells and pinealocytes. In this study, the temporal expression pattern of Otx2 was revealed in the rat brain, with special emphasis on the pineal gland throughout late embryonic and postnatal stages. Widespread high expression of Otx2 in the embryonic brain becomes progressively restricted in the adult to the pineal gland. Crx (cone-rod homeobox), a downstream target gene of Otx2, showed a pineal expression pattern similar to that of Otx2, although there was a distinct lag in time of onset. Otx2 protein was identified in pineal extracts and found to be localized in pinealocytes. Total pineal Otx2 mRNA did not show day-night variation, nor was it influenced by removal of the sympathetic input, indicating that the level of Otx2 mRNA appears to be independent of the photoneural input to the gland. Our results are consistent with the view that pineal expression of Otx2 is required for development and we hypothesize that it plays a role in the adult in controlling the expression of the cluster of genes associated with phototransduction and melatonin synthesis.

  19. In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain

    PubMed Central

    Fallon, James; Reid, Steve; Kinyamu, Richard; Opole, Isaac; Opole, Rebecca; Baratta, Janie; Korc, Murray; Endo, Tiffany L.; Duong, Alexander; Nguyen, Gemi; Karkehabadhi, Masoud; Twardzik, Daniel; Loughlin, Sandra

    2000-01-01

    The development of an in vivo procedure for the induction of massive proliferation, directed migration, and neurodifferentiation (PMD) in the damaged adult central nervous system would hold promise for the treatment of human neurodegenerative disorders such as Parkinson's disease. We investigated the in vivo induction of PMD in the forebrain of the adult rat by using a combination of 6-hydroxydopamine lesion of the substantia nigra dopaminergic neurons and infusions of transforming growth factor α (TGFα) into forebrain structures. Only in animals with both lesion and infusion of TGFα was there a rapid proliferation of forebrain stem cells followed by a timed migration of a ridge of neuronal and glial progenitors directed toward the region of the TGFα infusion site. Subsequently, increasing numbers of differentiated neurons were observed in the striatum. In behavioral experiments, there was a significant reduction of apomorphine-induced rotations in animals receiving the TGFα infusions. These results show that the brain contains stem cells capable of PMD in response to an exogenously administered growth factor. This finding has significant implications with respect to the development of treatments for both acute neural trauma and neurodegenerative diseases. PMID:11121069

  20. A Dietary Supplementation with Leucine and Antioxidants Is Capable to Accelerate Muscle Mass Recovery after Immobilization in Adult Rats

    PubMed Central

    Savary-Auzeloux, Isabelle; Magne, Hugues; Migné, Carole; Oberli, Marion; Breuillé, Denis; Faure, Magali; Vidal, Karine; Perrot, Marie; Rémond, Didier; Combaret, Lydie; Dardevet, Dominique

    2013-01-01

    Prolonged inactivity induces muscle loss due to an activation of proteolysis and decreased protein synthesis; the latter is also involved in the recovery of muscle mass. The aim of the present work was to explore the evolution of muscle mass and protein metabolism during immobilization and recovery and assess the effect of a nutritional strategy for counteracting muscle loss and facilitating recovery. Adult rats (6–8 months) were subjected to unilateral hindlimb casting for 8 days (I0–I8) and then permitted to recover for 10 to 40 days (R10–R40). They were fed a Control or Experimental diet supplemented with antioxidants/polyphenols (AOX) (I0 to I8), AOX and leucine (AOX + LEU) (I8 to R15) and LEU alone (R15 to R40). Muscle mass, absolute protein synthesis rate and proteasome activities were measured in gastrocnemius muscle in casted and non-casted legs in post prandial (PP) and post absorptive (PA) states at each time point. Immobilized gastrocnemius protein content was similarly reduced (-37%) in both diets compared to the non-casted leg. Muscle mass recovery was accelerated by the AOX and LEU supplementation (+6% AOX+LEU vs. Control, P<0.05 at R40) due to a higher protein synthesis both in PA and PP states (+23% and 31% respectively, Experimental vs. Control diets, P<0.05, R40) without difference in trypsin- and chymotrypsin-like activities between diets. Thus, this nutritional supplementation accelerated the recovery of muscle mass via a stimulation of protein synthesis throughout the entire day (in the PP and PA states) and could be a promising strategy to be tested during recovery from bed rest in humans. PMID:24312309

  1. Strength training at high versus low external resistance in older adults: effects on muscle volume, muscle strength, and force-velocity characteristics.

    PubMed

    Van Roie, Evelien; Delecluse, Christophe; Coudyzer, Walter; Boonen, Steven; Bautmans, Ivan

    2013-11-01

    Muscle adaptations can be induced by high-resistance exercise. Despite being potentially more suitable for older adults, low-resistance exercise protocols have been less investigated. We compared the effects of high- and low-resistance training on muscle volume, muscle strength, and force-velocity characteristics. Fifty-six older adults were randomly assigned to 12 weeks of leg press and leg extension training at either HIGH (2×10-15 repetitions at 80% of one repetition maximum (1RM)), LOW (1×80-100 repetitions at 20% of 1RM), or LOW+ (1×60 repetitions at 20% of 1RM, followed by 1×10-20 repetitions at 40% of 1RM). All protocols ended with muscle failure. Leg press and leg extension of 1RM were measured at baseline and post intervention and before the first training session in weeks 5 and 9. At baseline and post intervention, muscle volume (MV) was measured by CT-scan. A Biodex dynamometer evaluated knee extensor static peak torque in different knee angles (PT(stat90°), PT(stat120°), PT(stat150°)), dynamic peak torque at different speeds (PT(dyn60°s)(-1), PT(dyn180°s)(-1), PT(dyn240°s)(-1)), and speed of movement at 20% (S20), 40% (S40), and 60% (S60) of PTstat90°. HIGH and LOW+ resulted in greater improvements in 1RM strength than LOW (p<0.05). These differences were already apparent after week 5. Similar gains were found between groups in MV, PT(stat), PT(dyn60°s)(-1), and PT(dyn180°s)(-1). No changes were reported in speed of movement. HIGH tended to improve PT(dyn240°s)(-1) more than LOW or LOW+ (p=0.064). In conclusion, high- and low-resistance exercises ending with muscle failure may be similarly effective for hypertrophy. High-resistance training led to a higher increase in 1RM strength than low-resistance training (20% of 1RM), but this difference disappeared when using a mixed low-resistance protocol in which the resistance was intensified within a single exercise set (40% of 1RM). Our findings support the need for more research on low

  2. Effects of high-speed power training on muscle performance and braking speed in older adults.

    PubMed

    Sayers, Stephen P; Gibson, Kyle

    2012-01-01

    We examined whether high-speed power training (HSPT) improved muscle performance and braking speed using a driving simulator. 72 older adults (22 m, 50 f; age = 70.6 ± 7.3 yrs) were randomized to HSPT at 40% one-repetition maximum (1RM) (HSPT: n = 25; 3 sets of 12-14 repetitions), slow-speed strength training at 80%1RM (SSST: n = 25; 3 sets of 8-10 repetitions), or control (CON: n = 22; stretching) 3 times/week for 12 weeks. Leg press and knee extension peak power, peak power velocity, peak power force/torque, and braking speed were obtained at baseline and 12 weeks. HSPT increased peak power and peak power velocity across a range of external resistances (40-90% 1RM; P < 0.05) and improved braking speed (P < 0.05). Work was similar between groups, but perceived exertion was lower in HSPT (P < 0.05). Thus, the less strenuous HSPT exerted a broader training effect and improved braking speed compared to SSST.

  3. Gracilis muscle transposition as a workhorse flap for anal incontinence: Quality of life and functional outcome in adults

    PubMed Central

    Kalra, Guru Dayal Singh; Sharma, Amit Kumar; Shende, Kaustubh Sharad

    2016-01-01

    Background/Purpose: Anal incontinence is one of the most psychologically and socially debilitating conditions in an otherwise healthy individual. It can lead to social isolation, loss of self-esteem, self-confidence and depression. This study is devoted to the problem of anal incontinence in the adult patients. The aim of our study is to analyse the results of gracilis muscle transposition for anal incontinence and improvement in quality of life (QOL) of patients. Materials and Methods: This was a retrospective study. A total of 18 patients with complaint of anal incontinence were enrolled in this study. All patients were treated with gracilis muscle transposition. Results: All patients are continent, and there is an improvement in their QOL. Conclusion: Gracilis muscle transposition is a good option for patients of anal incontinence who are not treated by non-surgical means. PMID:28216815

  4. Time to Maximal Voluntary Isometric Contraction (MVC) for Five Different Muscle Groups in College Adults.

    ERIC Educational Resources Information Center

    Morris, A. F.; And Others

    1983-01-01

    College men and women were studied to ascertain the force-time components of a rapid voluntary muscle contraction for five muscle groups. Researchers found that the time required for full contraction differs: (1) in men and women; and (2) among the five muscle groups. (Authors/PP)

  5. Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle.

    PubMed

    Cho, Yoshitake; Hazen, Bethany C; Gandra, Paulo G; Ward, Samuel R; Schenk, Simon; Russell, Aaron P; Kralli, Anastasia

    2016-02-01

    Skeletal muscle mitochondrial content and oxidative capacity are important determinants of muscle function and whole-body health. Mitochondrial content and function are enhanced by endurance exercise and impaired in states or diseases where muscle function is compromised, such as myopathies, muscular dystrophies, neuromuscular diseases, and age-related muscle atrophy. Hence, elucidating the mechanisms that control muscle mitochondrial content and oxidative function can provide new insights into states and diseases that affect muscle health. In past studies, we identified Perm1 (PPARGC1- and ESRR-induced regulator, muscle 1) as a gene induced by endurance exercise in skeletal muscle, and regulating mitochondrial oxidative function in cultured myotubes. The capacity of Perm1 to regulate muscle mitochondrial content and function in vivo is not yet known. In this study, we use adeno-associated viral (AAV) vectors to increase Perm1 expression in skeletal muscles of 4-wk-old mice. Compared to control vector, AAV1-Perm1 leads to significant increases in mitochondrial content and oxidative capacity (by 40-80%). Moreover, AAV1-Perm1-transduced muscles show increased capillary density and resistance to fatigue (by 33 and 31%, respectively), without prominent changes in fiber-type composition. These findings suggest that Perm1 selectively regulates mitochondrial biogenesis and oxidative function, and implicate Perm1 in muscle adaptations that also occur in response to endurance exercise.

  6. Effects of Age, Sex, and Body Position on Orofacial Muscle Tone in Healthy Adults

    ERIC Educational Resources Information Center

    Dietsch, Angela M.; Clark, Heather M.; Steiner, Jessica N.; Solomon, Nancy Pearl

    2015-01-01

    Purpose: Quantification of tissue stiffness may facilitate identification of abnormalities in orofacial muscle tone and thus contribute to differential diagnosis of dysarthria. Tissue stiffness is affected by muscle tone as well as age-related changes in muscle and connective tissue. Method: The Myoton-3 measured tissue stiffness in 40 healthy…

  7. Muscle-Strengthening Activities and Participation among Adults in the United States

    ERIC Educational Resources Information Center

    Loustalot, Fleetwood; Carlson, Susan A.; Kruger, Judy; Buchner, David M.; Fulton, Janet E.

    2013-01-01

    Purpose: To describe those who reported meeting the "2008 Physical Activity Guidelines for Americans" ("2008 Guidelines") muscle-strengthening standard of 2 or more days per week, including all seven muscle groups, and to assess the type and location of muscle-strengthening activities performed. Method: Data from HealthStyles…

  8. A 9-wk docosahexaenoic acid-enriched supplementation improves endurance exercise capacity and skeletal muscle mitochondrial function in adult rats.

    PubMed

    Le Guen, Marie; Chaté, Valérie; Hininger-Favier, Isabelle; Laillet, Brigitte; Morio, Béatrice; Pieroni, Gérard; Schlattner, Uwe; Pison, Christophe; Dubouchaud, Hervé

    2016-02-01

    Decline in skeletal muscle mass and function starts during adulthood. Among the causes, modifications of the mitochondrial function could be of major importance. Polyunsaturated fatty (ω-3) acids have been shown to play a role in intracellular functions. We hypothesize that docosahexaenoic acid (DHA) supplementation could improve muscle mitochondrial function that could contribute to limit the early consequences of aging on adult muscle. Twelve-month-old male Wistar rats were fed a low-polyunsaturated fat diet and were given DHA (DHA group) or placebo (control group) for 9 wk. Rats from the DHA group showed a higher endurance capacity (+56%, P < 0.05) compared with control animals. Permeabilized myofibers from soleus muscle showed higher O2 consumptions (P < 0.05) in the DHA group compared with the control group, with glutamate-malate as substrates, both in basal conditions (i.e., state 2) and under maximal conditions (i.e., state 3, using ADP), along with a higher apparent Km for ADP (P < 0.05). Calcium retention capacity of isolated mitochondria was lower in DHA group compared with the control group (P < 0.05). Phospho-AMPK/AMPK ratio and PPARδ mRNA content were higher in the DHA group compared with the control group (P < 0.05). Results showed that DHA enhanced endurance capacity in adult animals, a beneficial effect potentially resulting from improvement in mitochondrial function, as suggested by our results on permeabilized fibers. DHA supplementation could be of potential interest for the muscle function in adults and for fighting the decline in exercise tolerance with age that could imply energy-sensing pathway, as suggested by changes in phospho-AMPK/AMPK ratio.

  9. A novel approach to collecting satellite cells from adult skeletal muscles on the basis of their stress tolerance.

    PubMed

    Shigemoto, Taeko; Kuroda, Yasumasa; Wakao, Shohei; Dezawa, Mari

    2013-07-01

    Stem cells are generally collected using flow cytometry, but this method is not applicable when the cell surface marker is not well determined. Satellite cells, which are skeletal muscle stem cells, have the ability to regenerate damaged muscles and are expected to be applicable for treatment of muscle degeneration. Although the transcription factor Pax7 is a known specific marker of satellite cells, it is not located on the cell surface and therefore flow cytometry is not directly applicable. In the present study, we turned our attention to the stress tolerance of adult stem cells, and we propose long-term trypsin incubation (LTT) as a novel approach to collecting satellite cells from mouse and human skeletal muscles. LTT led to a remarkable increase in the ratio of Pax7(+) cells that retain normal myogenic stem cell function. In particular, human Pax7(+) cells made up approximately 30% of primary cultured cells, whereas after LTT, the ratio of Pax7(+) cells increased up to ∼80%, and the ratio of Pax7(+) and/or MyoD(+) myogenic cells increased to ∼95%. Once transplanted, LTT-treated cells contributed to subsequent muscle regeneration following repetitive muscle damage without additional cell transplantation. The stress tolerance of Pax7(+) cells is related to heat shock protein 27 and αB-crystallin, members of the small heat shock protein family. This approach, based on the stress resistance of adult stem cells, is a safe and inexpensive method of efficiently collecting human satellite cells and may also be used for collecting other tissue stem cells whose surface marker is unknown.

  10. Potential of adult mammalian lumbosacral spinal cord to execute and acquire improved locomotion in the absence of supraspinal input

    NASA Technical Reports Server (NTRS)

    Edgerton, V. R.; Roy, R. R.; Hodgson, J. A.; Prober, R. J.; de Guzman, C. P.; de Leon, R.

    1992-01-01

    The neural circuitry of the lumbar spinal cord can generate alternating extension and flexion of the hindlimbs. The hindlimbs of adult cats with complete transection of the spinal cord at a low thoracic level (T12-T13) can perform full weight-supporting locomotion on a treadmill belt moving at a range of speeds. Some limitations in the locomotor capacity can be associated with a deficit in the recruitment level of the fast extensors during the stance phase and the flexors during the swing phase of a step cycle. The level of locomotor performance, however, can be enhanced by daily training on a treadmill while emphasizing full weight-support stepping and by providing appropriately timed sensory stimulation, loading, and/or pharmacologic stimulation of the hindlimb neuromuscular apparatus. Furthermore, there appears to be an interactive effect of these interventions. For example, the maximum treadmill speed that a spinal adult cat can attain and maintain is significantly improved with daily full weight-supporting treadmill training, but progressive recruitment of fast extensors becomes apparent only when the hindlimbs are loaded by gently pulling down on the tail during the stepping. Stimulation of the sural nerve at the initiation of the flexion phase of the step cycle can likewise markedly improve the locomotor capability. Administration of clonidine, in particular in combination with an elevated load, resulted in the most distinct and consistent alternating bursts of electromyographic activity during spinal stepping. These data indicate that the spinal cord has the ability to execute alternating activation of the extensor and flexor musculature of the hindlimbs (stepping) and that this ability can be improved by several interventions such as training, sensory stimulation, and use of some pharmacologic agents. Thus, it appears that the spinal cord, without supraspinal input, is highly plastic and has the potential to "learn," that is, to acquire and improve its

  11. Relationship between Occlusal Force Distribution and the Activity of Masseter and Anterior Temporalis Muscles in Asymptomatic Young Adults

    PubMed Central

    Wieczorek, Aneta; Loster, Bartlomiej W.

    2013-01-01

    Healthy subjects have a prevalent side on which they display higher-muscle activity during clenching. The relationship between symmetry of masseter muscle (MM) and anterior temporalis (TA) muscle activities and occlusion has been evaluated on the basis of physiological parameters. The aim of the present study was to investigate whether the symmetry of surface EMG (sEMG) activity in asymptomatic young adults is related to symmetry of occlusal contacts. Material. The study population consisted of seventy-two 18-year-old subjects with no temporomandibular disorder (TMD) symptoms. Method. All the participants underwent an sEMG recording with an 8-channel electromyograph (BioEMG III). A T-Scan III evolution 7.01 device was used to analyze the occlusal contact points. Results. The correlation between the activity of right (R) and left (L) TA and the percentage of occlusal contacts was assessed, but no significant differences were found between the RMM and LMM muscles. The differences in the medium values of sEMG between males and females were not statistically significant. Equilibrated muscular activity between RTA and LTA occurred when occlusal contacts reached the percentage of 65% on the left side. Conclusion. The symmetry of sEMG activity in asymptomatic young adults is not related to symmetry of occlusal contacts. PMID:23509713

  12. The immunophilin ligand FK506, but not the P38 kinase inhibitor SB203580, improves function of adult rat muscle reinnervated from transplants of embryonic neurons.

    PubMed

    Grumbles, R M; Casella, G T B; Rudinsky, M J; Godfrey, S; Wood, P M; Thomas, C K

    2005-01-01

    Injury to the adult CNS often involves death of motoneurons, resulting in the paralysis and progressive atrophy of muscle. There is no effective therapy to replace motoneurons in the CNS. Our strategy to replace neurons and to rescue denervated muscles is to transplant dissociated embryonic day 14-15 (E14-15) ventral spinal cord cells into the distal stump of a peripheral nerve near the denervated muscles. Here, we test whether long-term delivery of two pharmacological inhibitors to denervated muscle, FK506 or SB203580, enhances reinnervation of muscle from embryonic cells transplanted in the tibial nerve of adult Fischer rats. FK506, SB203580 (2.5 mg/kg) or saline was delivered under the fascia of the medial gastrocnemius muscle for 4 weeks, beginning when muscles were denervated by section of the sciatic nerve. After 1 week of nerve degeneration, one million E14-15 ventral spinal cord cells were transplanted into the distal tibial nerve stump of each rat in the three treatment groups. Ten weeks later, all cell transplants had neuron-specific nuclear protein (NeuN) positive neurons. Neuron survival and axon regeneration were similar across treatments. An average (+/-S.E.) of 210+/-66, 100+/-36 and 176+/-58 myelinated axons grew distally from the cell transplants of rats with muscles treated with FK506, SB203580 or saline, respectively. Regenerating axons in muscles of all three treatments groups were detected with antibodies against phosphorylated neurofilaments and synaptophysin, and motor end plates were labeled with alpha-bungarotoxin. Muscles of rats that received transplants of media only had no axon growth, indicating that the muscles were denervated. The mean muscle fiber areas of rats that received cell transplants and had long-term delivery of FK506, SB203580 or saline to muscles were significantly larger than those of denervated muscle fibers. Thus, cell transplantation reduced muscle atrophy. Transplantation of embryonic cells also resulted in

  13. p38α MAPK regulates adult muscle stem cell fate by restricting progenitor proliferation during postnatal growth and repair.

    PubMed

    Brien, Patrick; Pugazhendhi, Dhamayanthi; Woodhouse, Samuel; Oxley, David; Pell, Jennifer M

    2013-08-01

    Stem cell function is essential for the maintenance of adult tissue homeostasis. Controlling the balance between self-renewal and differentiation is crucial to maintain a receptive satellite cell pool capable of responding to growth and regeneration cues. The mitogen-activated protein kinase p38α has been implicated in the regulation of these processes but its influence in adult muscle remains unknown. Using conditional satellite cell p38α knockout mice we have demonstrated that p38α restricts excess proliferation in the postnatal growth phase while promoting timely myoblast differentiation. Differentiation was still able to occur in the p38α-null satellite cells, however, but was delayed. An absence of p38α resulted in a postnatal growth defect along with the persistence of an increased reservoir of satellite cells into adulthood. This population was still capable of responding to cardiotoxin-induced injury, resulting in complete, albeit delayed, regeneration, with further enhancement of the satellite cell population. Increased p38γ phosphorylation accompanied the absence of p38α, and inhibition of p38γ ex vivo substantially decreased the myogenic defect. We have used genome-wide transcriptome analysis to characterize the changes in expression that occur between resting and regenerating muscle, and the influence p38α has on these expression profiles. This study provides novel evidence for the fundamental role of p38α in adult muscle homeostasis in vivo.

  14. Chiton myogenesis: perspectives for the development and evolution of larval and adult muscle systems in molluscs.

    PubMed

    Wanninger, Andreas; Haszprunar, Gerhard

    2002-02-01

    We investigated muscle development in two chiton species, Mopalia muscosa and Chiton olivaceus, from embryo hatching until 10 days after metamorphosis. The anlagen of the dorsal longitudinal rectus muscle and a larval prototroch muscle ring are the first detectable muscle structures in the early trochophore-like larva. Slightly later, a ventrolaterally situated pair of longitudinal muscles appears, which persists through metamorphosis. In addition, the anlagen of the putative dorsoventral shell musculature and the first fibers of a muscular grid, which is restricted to the pretrochal region and consists of outer ring and inner diagonal muscle fibers, are generated. Subsequently, transversal muscle fibers form underneath each future shell plate and the ventrolateral enrolling muscle is established. At metamorphic competence, the dorsoventral shell musculature consists of numerous serially repeated, intercrossing muscle fibers. Their concentration into seven (and later eight) functional shell plate muscle bundles starts after the completion of metamorphosis. The larval prototroch ring and the pretrochal muscle grid are lost at metamorphosis. The structure of the apical grid and its atrophy during metamorphosis suggests ontogenetic repetition of (parts of) the original body-wall musculature of a proposed worm-shaped molluscan ancestor. Moreover, our data show that the "segmented" character of the polyplacophoran shell musculature is a secondary condition, thus contradicting earlier theories that regarded the Polyplacophora (and thus the entire phylum Mollusca) as primarily eumetameric (annelid-like). Instead, we propose an unsegmented trochozoan ancestor at the base of molluscan evolution.

  15. Stem Cells in Mammalian Gonads.

    PubMed

    Wu, Ji; Ding, Xinbao; Wang, Jian

    Stem cells have great value in clinical application because of their ability to self-renew and their potential to differentiate into many different cell types. Mammalian gonads, including testes for males and ovaries for females, are composed of germline and somatic cells. In male mammals, spermatogonial stem cells maintain spermatogenesis which occurs continuously in adult testis. Likewise, a growing body of evidence demonstrated that female germline stem cells could be found in mammalian ovaries. Meanwhile, prior studies have shown that somatic stem cells exist in both testes and ovaries. In this chapter, we focus on mammalian gonad stem cells and discuss their characteristics as well as differentiation potentials.

  16. Safe and bodywide muscle transduction in young adult Duchenne muscular dystrophy dogs with adeno-associated virus.

    PubMed

    Yue, Yongping; Pan, Xiufang; Hakim, Chady H; Kodippili, Kasun; Zhang, Keqing; Shin, Jin-Hong; Yang, Hsiao T; McDonald, Thomas; Duan, Dongsheng

    2015-10-15

    The ultimate goal of muscular dystrophy gene therapy is to treat all muscles in the body. Global gene delivery was demonstrated in dystrophic mice more than a decade ago using adeno-associated virus (AAV). However, translation to affected large mammals has been challenging. The only reported attempt was performed in newborn Duchenne muscular dystrophy (DMD) dogs. Unfortunately, AAV injection resulted in growth delay, muscle atrophy and contracture. Here we report safe and bodywide AAV delivery in juvenile DMD dogs. Three ∼2-m-old affected dogs received intravenous injection of a tyrosine-engineered AAV-9 reporter or micro-dystrophin (μDys) vector at the doses of 1.92-6.24 × 10(14) viral genome particles/kg under transient or sustained immune suppression. DMD dogs tolerated injection well and their growth was not altered. Hematology and blood biochemistry were unremarkable. No adverse reactions were observed. Widespread muscle transduction was seen in skeletal muscle, the diaphragm and heart for at least 4 months (the end of the study). Nominal expression was detected in internal organs. Improvement in muscle histology was observed in μDys-treated dogs. In summary, systemic AAV gene transfer is safe and efficient in young adult dystrophic large mammals. This may translate to bodywide gene therapy in pediatric patients in the future.

  17. Effects of restrictive clothing on lumbar range of motion and trunk muscle activity in young adult worker manual material handling.

    PubMed

    Eungpinichpong, Wichai; Buttagat, Vitsarut; Areeudomwong, Pattanasin; Pramodhyakul, Noppol; Swangnetr, Manida; Kaber, David; Puntumetakul, Rungthip

    2013-11-01

    The objective of this study was to examine the effect of wearing restrictive trousers on lumbar spine movement, trunk muscle activity and low back discomfort (LBD) in simulations of manual material handling (MMH) tasks. Twenty-eight young adults participated in the study performing box lifting, liquid container handling while squatting, and forward reaching while sitting on a task chair when wearing tight pants (sizes too small for the wearer) vs. fit pants (correct size according to anthropometry). Each task was repeated three times and video recordings were used as a basis for measuring lumbar range of motion (LRoM). The response was normalized in terms on baseline hip mobility. Trunk muscle activity of rectus abdominis (RA) and erector spinae (ES) muscles were also measured in each trial and normalized. At the close of each trial, participants rated LBD using a visual analog scale. Results revealed significant effects of both pants and task types on the normalized LRoM, trunk muscle activity and subjective ratings of LBD. The LRoM was higher and trunk muscle (ES) activity was lower for participants when wearing tight pants, as compared to fit pants. Discomfort ratings were significantly higher for tight pants than fit. These results provide guidance for recommendations on work clothing fit in specific types of MMH activities in order to reduce the potential of low-back pain among younger workers in industrial companies.

  18. Transforming growth factor type beta specifically stimulates synthesis of proteoglycan in human adult arterial smooth muscle cells.

    PubMed Central

    Chen, J K; Hoshi, H; McKeehan, W L

    1987-01-01

    Myo-intimal proteoglycan metabolism is thought to be important in blood vessel homeostasis, blood clotting, atherogenesis, and atherosclerosis. Human platelet-derived transforming growth factor type beta (TGF-beta) specifically stimulated synthesis of at least two types of chondroitin sulfate proteoglycans in nonproliferating human adult arterial smooth muscle cells in culture. Stimulation of smooth muscle cell proteoglycan synthesis by smooth muscle cell growth promoters (epidermal growth factor, platelet-derived growth factor, and heparin-binding growth factors) was less than 20% of that elicited by TGF-beta. TGF-beta neither significantly stimulated proliferation of quiescent smooth muscle cells nor inhibited proliferating cells. The extent of TGF-beta stimulation of smooth muscle cell proteoglycan synthesis was similar in both nonproliferating and growth-stimulated cells. TGF-beta, which is a reversible inhibitor of endothelial cell proliferation, had no comparable effect on endothelial cell proteoglycan synthesis. These results are consistent with the hypothesis that TGF-beta is a cell-type-specific regulator of proteoglycan synthesis in human blood vessels and may contribute to the myo-intimal accumulation of proteoglycan in atherosclerotic lesions. Images PMID:3474655

  19. Adaptations to exercise training within skeletal muscle in adults with type 2 diabetes or impaired glucose tolerance: a systematic review.

    PubMed

    Wang, Yi; Simar, David; Fiatarone Singh, Maria A

    2009-01-01

    The aim of this investigation was to review morphological and metabolic adaptations within skeletal muscle to exercise training in adults with type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). A comprehensive, systematic database search for manuscripts was performed from 1966 to March 2008 using computerized databases, including Medline, Premedline, CINAHL, AMED, EMBASE and SportDiscus. Three reviewers independently assessed studies for potential inclusion (exposure to exercise training, T2DM or IGT, muscle biopsy performed). A total of 18 exercise training studies were reviewed. All morphological and metabolic outcomes from muscle biopsies were collected. The metabolic outcomes were divided into six domains: glycogen, glucose facilitated transporter 4 (GLUT4) and insulin signalling, enzymes, markers of inflammation, lipids metabolism and so on. Beneficial adaptations to exercise were seen primarily in muscle fiber area and capillary density, glycogen, glycogen synthase and GLUT4 protein expressions. Few randomized controlled trials including muscle biopsy data existed, with a small number of subjects involved. More trials, especially robustly designed exercise training studies, are needed in this field. Future research should focus on the insulin signalling pathway to better understand the mechanism of the improvements in insulin sensitivity and glucose homeostasis in response to various modalities and doses of exercise in this cohort.

  20. Site-specific Mtm1 mutagenesis by an AAV-Cre vector reveals that myotubularin is essential in adult muscle.

    PubMed

    Joubert, Romain; Vignaud, Alban; Le, Mickaël; Moal, Christelle; Messaddeq, Nadia; Buj-Bello, Anna

    2013-05-01

    Manipulation of the mouse genome by site-specific mutagenesis has been extensively used to study gene function and model human disorders. Mouse models of myotubular myopathy (XLMTM), a severe congenital muscular disorder due to loss-of-function mutations in the MTM1 gene, have been generated by homologous recombination and shown that myotubularin is essential for skeletal muscle. However, since the Mtm1 deletion occurred constitutively or shortly after birth in these mice, it is not known whether myotubularin is required during adulthood, an important issue in the context of not only muscle biology but also therapies. To delete the Mtm1 gene in adult muscle fibers, we constructed a recombinant adeno-associated vector (AAV) that expresses the Cre recombinase under the muscle-specific desmin promoter. We report that a single injection of this vector into muscles of 3-month-old Mtm1 conditional mice leads to a myotubular myopathy phenotype with myofiber atrophy, disorganization of organelle positioning, such as mitochondria and nuclei, T-tubule defects and severe muscle weakness. In addition, our results show that MTM1-related atrophy and dysfunction correlate with abnormalities in satellite cell number and markers of autophagy, protein synthesis and neuromuscular junction transmission. The expression level of atrogenes was also analyzed. Therefore, we provide a valuable tissue model that recapitulates the main features of the disease, and it is useful to study pathogenesis and evaluate therapeutic strategies. We establish the proof-of-concept that myotubularin is required for the proper function of skeletal muscle during adulthood, suggesting that therapies will be required for the entire life of XLMTM patients.

  1. Spaceflight effects on adult rat muscle protein, nucleic acids, and amino acids

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1986-01-01

    Exposure to conditions of weightlessness has been associated with decrements in muscle mass and strength. The present studies were undertaken to determine muscle responses at the cellular level. Male Sprague-Dawley rats (360-410 g) were exposed to 7 days of weightlessness during the Spacelab-3 shuttle flight (May 1985). Animals were killed 12 h postflight, and soleus (S), gastrocnemius (G), and extensor digitorum longus (EDL) muscles were excised. Muscle protein, RNA, and DNA were extracted and quantified. Differential muscle atrophy was accompanied by a significant (P less than 0.05) reduction in total protein only in S muscles. There were no significant changes in protein concentration (mg/g) in the muscles examined. In S muscles from flight animals, sarcoplasmic protein accounted for a significantly greater proportion of total protein that in ground controls (37.5 vs. 32.5%). Tissue concentrations (nmol/g) of asparagine-aspartate, glutamine-glutamate, glycine, histidine, and lysine were significantly reduced (from 17 to 63%) in S muscles from flight animals, but only glutamine-glutamate levels were decreased in the G and EDL. Muscle DNA content (microgram) was unchanged in the tissues examined, but S muscle DNA concentration (micrograms/mg) increased 27%. RNA content (micrograms) was significantly (P less than 0.025) reduced in S (-28%) and G(-22%) muscles following spaceflight. These results identify specific alterations in rat skeletal muscle during short term (7-day) exposure to weightlessness and compare favorably with observations previously obtained from ground-based suspension simulations.

  2. NF-KappaB in Long-Term Memory and Structural Plasticity in the Adult Mammalian Brain

    PubMed Central

    Kaltschmidt, Barbara; Kaltschmidt, Christian

    2015-01-01

    The transcription factor nuclear factor kappaB (NF-κB) is a well-known regulator of inflammation, stress, and immune responses as well as cell survival. In the nervous system, NF-κB is one of the crucial components in the molecular switch that converts short- to long-term memory—a process that requires de novo gene expression. Here, the researches published on NF-κB and downstream target genes in mammals will be reviewed, which are necessary for structural plasticity and long-term memory, both under normal and pathological conditions in the brain. Genetic evidence has revealed that NF-κB regulates neuroprotection, neuronal transmission, and long-term memory. In addition, after genetic ablation of all NF-κB subunits, a severe defect in hippocampal adult neurogenesis was observed during aging. Proliferation of neural precursors is increased; however, axon outgrowth, synaptogenesis, and tissue homeostasis of the dentate gyrus are hampered. In this process, the NF-κB target gene PKAcat and other downstream target genes such as Igf2 are critically involved. Therefore, NF-κB activity seems to be crucial in regulating structural plasticity and replenishment of granule cells within the hippocampus throughout the life. In addition to the function of NF-κB in neurons, we will discuss on a neuroinflammatory role of the transcription factor in glia. Finally, a model for NF-κB homeostasis on the molecular level is presented, in order to explain seemingly the contradictory, the friend or foe, role of NF-κB in the nervous system. PMID:26635522

  3. Mammalian pheromones.

    PubMed

    Liberles, Stephen D

    2014-01-01

    Mammalian pheromones control a myriad of innate social behaviors and acutely regulate hormone levels. Responses to pheromones are highly robust, reproducible, and stereotyped and likely involve developmentally predetermined neural circuits. Here, I review several facets of pheromone transduction in mammals, including (a) chemosensory receptors and signaling components of the main olfactory epithelium and vomeronasal organ involved in pheromone detection; (b) pheromone-activated neural circuits subject to sex-specific and state-dependent modulation; and (c) the striking chemical diversity of mammalian pheromones, which range from small, volatile molecules and sulfated steroids to large families of proteins. Finally, I review (d) molecular mechanisms underlying various behavioral and endocrine responses, including modulation of puberty and estrous; control of reproduction, aggression, suckling, and parental behaviors; individual recognition; and distinguishing of own species from predators, competitors, and prey. Deconstruction of pheromone transduction mechanisms provides a critical foundation for understanding how odor response pathways generate instinctive behaviors.

  4. Mammalian Pheromones

    PubMed Central

    Liberles, Stephen D.

    2015-01-01

    Mammalian pheromones control a myriad of innate social behaviors and acutely regulate hormone levels. Responses to pheromones are highly robust, reproducible, and stereotyped and likely involve developmentally predetermined neural circuits. Here, I review several facets of pheromone transduction in mammals, including (a) chemosensory receptors and signaling components of the main olfactory epithelium and vomeronasal organ involved in pheromone detection; (b) pheromone-activated neural circuits subject to sex-specific and state-dependent modulation; and (c) the striking chemical diversity of mammalian pheromones, which range from small, volatile molecules and sulfated steroids to large families of proteins. Finally, I review (d ) molecular mechanisms underlying various behavioral and endocrine responses, including modulation of puberty and estrous; control of reproduction, aggression, suckling, and parental behaviors; individual recognition; and distinguishing of own species from predators, competitors, and prey. Deconstruction of pheromone transduction mechanisms provides a critical foundation for understanding how odor response pathways generate instinctive behaviors. PMID:23988175

  5. The Association of Growth Hormone Parameters with Skeletal Muscle Phosphocreatine Recovery in Adult Men

    PubMed Central

    Stanley, Takara L.; Sun, Noelle; Hrovat, Mirko I.; Systrom, David M.; Grinspoon, Steven K.

    2011-01-01

    Context: Previous studies have suggested a relationship between GH and mitochondrial function. However, little is known about the relationship of specific GH indices and in vivo measures of mitochondrial function in humans. Objective: The objective of this study was to determine the association between GH, IGF-I, and phosphocreatine (PCr) recovery, a measure of mitochondrial function, in otherwise healthy adults. Design: Thirty-seven healthy men and women were studied at a single university medical center. Subjects underwent GH stimulation testing with GH releasing hormone-arginine and measurement of IGF-I. Mitochondrial function was determined by PCr recovery after submaximal exercise by 31Phosphorous magnetic resonance spectroscopy. Subjects underwent assessment of lean and fat mass with use of dual energy X-ray absorptiometry. Results: There were no differences in PCr recovery between men and women (men 20.7±1.5 vs. women 24.8±1.4 mm/min; P > 0.05). IGF-I (r = 0.33; P = 0.04) was associated with PCr recovery in all subjects. Among men, IGF-I (r = 0.69; P = 0.003), peak stimulated GH (r = 0.52; P = 0.04), and GH area under the curve (AUC) (r = 0.53; P = 0.04) were significantly associated with PCr recovery. However, neither IGF-I, peak stimulated GH, nor GH AUC (all P > 0.05) were associated with PCr recovery in women. After adjusting for age, race, and physical activity, IGF-I remained significantly associated with PCr recovery (β = 0.10; P = 0.02) among men. Conclusions: IGF-I, peak stimulated GH, and GH AUC are associated with skeletal muscle PCr recovery in men. PMID:21177784

  6. Strong relationships exist between muscle volume, joint power and whole-body external mechanical power in adults and children.

    PubMed

    O'Brien, Thomas D; Reeves, Neil D; Baltzopoulos, Vasilios; Jones, David A; Maganaris, Constantinos N

    2009-06-01

    The present study investigated whether differences between adults and children in mechanical power during single-joint knee extension tasks and the complex multijoint task of jumping could be explained by differences in the quadriceps femoris muscle volume. Peak power was calculated during squat jumps, from the integral of the vertical force measured by a force plate, and during concentric knee extensions at 30, 90, 120, 180 and 240 deg s(-1), and muscle volume was measured from magnetic resonance images for 10 men, 10 women, 10 prepubertal boys and 10 prepubertal girls. Peak power during jumping and isokinetic knee extension was significantly higher in men than in women, and in both adult groups compared with children (P < 0.01), although there were no differences between boys and girls. When power was normalized to muscle volume, the intergroup differences ceased to exist for both tasks. Peak power correlated significantly with quadriceps volume (P < 0.01), with r(2) values of 0.8, 0.86, 0.81, 0.78 and 0.81 from isokinetic knee extension at angular velocities of 30, 90, 120, 180 and 240 deg s(-1), respectively, and with an r(2) value of 0.9 from squat jumps. These results indicate that the quadriceps femoris muscle volume accounts largely for the increase in power that occurs with maturation in the two genders not only in kinematically constrained knee extensions but also in multijoint tasks. Future studies should examine the role of other factors relating to the generation and transmission of contractile power, such as muscle architecture, tendon stiffness and external mechanical leverage.

  7. Gestational protein restriction impairs insulin-regulated glucose transport mechanisms in gastrocnemius muscles of adult male offspring.

    PubMed

    Blesson, Chellakkan S; Sathishkumar, Kunju; Chinnathambi, Vijayakumar; Yallampalli, Chandrasekhar

    2014-08-01

    Type II diabetes originates from various genetic and environmental factors. Recent studies showed that an adverse uterine environment such as that caused by a gestational low-protein (LP) diet can cause insulin resistance in adult offspring. The mechanism of insulin resistance induced by gestational protein restriction is not clearly understood. Our aim was to investigate the role of insulin signaling molecules in gastrocnemius muscles of gestational LP diet-exposed male offspring to understand their role in LP-induced insulin resistance. Pregnant Wistar rats were fed a control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery and a normal diet after weaning. Only male offspring were used in this study. Glucose and insulin responses were assessed after a glucose tolerance test. mRNA and protein levels of molecules involved in insulin signaling were assessed at 4 months in gastrocnemius muscles. Muscles were incubated ex vivo with insulin to evaluate insulin-induced phosphorylation of insulin receptor (IR), Insulin receptor substrate-1, Akt, and AS160. LP diet-fed rats gained less weight than controls during pregnancy. Male pups from LP diet-fed mothers were smaller but exhibited catch-up growth. Plasma glucose and insulin levels were elevated in LP offspring when subjected to a glucose tolerance test; however, fasting levels were comparable. LP offspring showed increased expression of IR and AS160 in gastrocnemius muscles. Ex vivo treatment of muscles with insulin showed increased phosphorylation of IR (Tyr972) in controls, but LP rats showed higher basal phosphorylation. Phosphorylation of Insulin receptor substrate-1 (Tyr608, Tyr895, Ser307, and Ser318) and AS160 (Thr642) were defective in LP offspring. Further, glucose transporter type 4 translocation in LP offspring was also impaired. A gestational LP diet leads to insulin resistance in adult offspring by a mechanism involving inefficient insulin-induced IR, Insulin receptor

  8. REDUCED RATE OF KNEE EXTENSOR TORQUE DEVELOPMENT IN OLDER ADULTS WITH KNEE OSTEOARTHRITIS IS ASSOCIATED WITH INTRINSIC MUSCLE CONTRACTILE DEFICITS

    PubMed Central

    Callahan, Damien M.; Tourville, Timothy W.; Slauterbeck, James R.; Ades, Philip A.; Stevens-Lapsley, Jennifer; Beynnon, Bruce D.; Toth, Michael J.

    2015-01-01

    We examined the effect of knee osteoarthritis on the rate of torque development (RTD) of the knee extensors in older adults with advanced-stage knee osteoarthritis (OA; n=15) and recreationally-active controls (n=15) of similar age, sex and health status, as well as the relationship between RTD and the size and contractility of single muscle fibers. OA participants had lower RTD when expressed in absolute terms (Nm/ms). There were sex differences in peak RTD (P<0.05), with greater RTD in men, but no group by sex interaction effects for any variables. The lower RTD in OA versus controls was not explained by variation between groups in the fiber type admixture of the muscle, and was mitigated when RTD was normalized to peak torque (PT). In knee OA volunteers, we found strong correlations between the RTD expressed relative to PT and the velocity of contraction of single myosin heavy chain (MHC) I and IIA/X muscle fibers (r=0.652 and 0.862; both P<0.05) and power output of MHC I fibers (r=0.642; P<0.05). In controls, RTD relative to PT was related to fiber cross-sectional area of MHC IIA/X fibers (r=0.707; P<0.05), but not measures of single fiber contractile performance. To our knowledge, these results represent the first demonstration that variation in whole muscle contractile kinetics in patients with advanced-stage knee osteoarthritis and healthy older adults is related, in part, to the size and function of single muscle fibers. PMID:26343257

  9. Expression of the Troponin C at 41C Gene in Adult Drosophila Tubular Muscles Depends upon Both Positive and Negative Regulatory Inputs.

    PubMed

    Chechenova, Maria B; Maes, Sara; Cripps, Richard M

    2015-01-01

    Most animals express multiple isoforms of structural muscle proteins to produce tissues with different physiological properties. In Drosophila, the adult muscles include tubular-type muscles and the fibrillar indirect flight muscles. Regulatory processes specifying tubular muscle fate remain incompletely understood, therefore we chose to analyze the transcriptional regulation of TpnC41C, a Troponin C gene expressed in the tubular jump muscles, but not in the fibrillar flight muscles. We identified a 300-bp promoter fragment of TpnC41C sufficient for the fiber-specific reporter expression. Through an analysis of this regulatory element, we identified two sites necessary for the activation of the enhancer. Mutations in each of these sites resulted in 70% reduction of enhancer activity. One site was characterized as a binding site for Myocyte Enhancer Factor-2. In addition, we identified a repressive element that prevents activation of the enhancer in other muscle fiber types. Mutation of this site increased jump muscle-specific expression of the reporter, but more importantly reporter expression expanded into the indirect flight muscles. Our findings demonstrate that expression of the TpnC41C gene in jump muscles requires integration of multiple positive and negative transcriptional inputs. Identification of the transcriptional regulators binding the cis-elements that we identified will reveal the regulatory pathways controlling muscle fiber differentiation.

  10. Pumping Iron in Australia: Prevalence, Trends and Sociodemographic Correlates of Muscle Strengthening Activity Participation from a National Sample of 195,926 Adults

    PubMed Central

    Pedisic, Zeljko; van Uffelen, Jannique G. Z.; Charity, Melanie J.; Harvey, Jack T.; Banting, Lauren K.; Vergeer, Ineke; Biddle, Stuart J. H.; Eime, Rochelle M.

    2016-01-01

    Objective The current Australian Physical Activity Guidelines recommend that adults engage in regular muscle-strengthening activity (e.g. strength or resistance training). However, public health surveillance studies describing the patterns and trends of population-level muscle-strengthening activity participation are sparse. The aim of this study is to examine the prevalence, trends and sociodemographic correlates of muscle-strengthening activity participation in a national-representative sample of Australians aged 15 years and over. Methods Between 2001 and 2010, quarterly cross-sectional national telephone surveys were conducted as part of the Australian Sports Commission's 'Exercise, Recreation and Sport Survey'. Pooled population-weighted proportions were calculated for reporting: [i] no muscle-strengthening activity; [ii] insufficient muscle-strengthening activity, and [iii] sufficient muscle-strengthening activity. Associations with sociodemographic variables were assessed using multiple logistic regression analyses. Results Out of 195,926 participants, aged 15–98 years, only 10.4% (95% CI: 10.1–10.7) and 9.3% (95% CI: 9.1–9.5) met the muscle-strengthening activity recommendations in the past two weeks and in the past year, respectively. Older adults (50+ years), and those living in socioeconomically disadvantaged, outer regional/remote areas and with lower education were less likely to report sufficient muscle-strengthening activity (p<0.001). Over the 10-year monitoring period, there was a significant increase in the prevalence of sufficient muscle-strengthening activity (6.4% to 12.0%, p-value for linear trend <0.001). Conclusions A vast majority of Australian adults did not engage in sufficient muscle-strengthening activity. There is a need for public health strategies to support participation in muscle-strengthening activity in this population. Such strategies should target older and lower educated adults, and those living in socioeconomically

  11. Horse soleus muscle: postural sensor or vestigial structure?

    PubMed

    Meyers, Ron A; Hermanson, John W

    2006-10-01

    The soleus muscle of horses is rather diminutive with respect to the overall size of adjacent synergist muscles in the hind limb of the horse. Whether or not such a muscle might be vestigial or may be providing some essential function has not been determined. We have studied the horse's soleus muscle using histochemical (ATPase), immunocytochemical (myosin isoform identification), and SDS-PAGE analysis to demonstrate that it is largely composed of 100% type I, presumed slow-twitch fibers. Only one soleus muscle studied (out of 13 adult horses) contained any type II muscle fibers. Given this consistent high percentage of slow-oxidative fibers, we hypothesized that the soleus muscle could have a significant role in proprioceptive function, essentially functioning as a proprioceptive organ instead of a significant force-generating muscle during locomotion. We tested this by examining three whole soleus muscles and assessing their muscle spindle content, which proved to have a spindle index of about 12. This value provided equivocal support for the hypothesis since it did not approach values reported for other mammalian proprioceptive muscles that were approximately 40-50 spindles per gram of muscle mass. Other parameters, such as motoneuron number and muscle unit size, may be useful in understanding these data.

  12. Regulatory mechanisms and the role of calcium and potassium channels controlling supercontractile crop muscles in adult Phormia regina.

    PubMed

    Solari, Paolo; Stoffolano, John G; Fitzpatrick, Joanna; Gelperin, Alan; Thomson, Alan; Talani, Giuseppe; Sanna, Enrico; Liscia, Anna

    2013-09-01

    Bioassays and electrophysiological recordings were conducted in the adult blowfly Phormia regina to provide new insights into the regulatory mechanisms governing the crop filling and emptying processes of the supercontractile crop muscles. The cibarial pump drives ingestion. Simultaneous multisite extracellular recordings show that crop lobe (P5) distension during ingestion of a 4.7 μl sugar meal does not require muscle activity by any of the other pumps of the system. Conversely, pumping of fluids toward the anterior of the crop system during crop emptying is brought about by active muscle contraction, in the form of a highly coordinated peristaltic wave starting from P5 and progressively propagating to P6, P4 and P3 pumps, with P5 contracting with a frequency about 3.4 times higher than the other pumps. The crop contraction rate is also modulated by hemolymph-borne factors such as sugars, through ligand recognition at a presumptive receptor site rather than by an osmotic effect, as assessed by both behavioural and electrophysiological experiments. In this respect, sugars of equal osmolarity produce different effects, glucose being inhibitory and mannose ineffective for crop muscles, while trehalose enhances crop activity. Finally, voltage and current clamp experiments show that the muscle action potentials (mAPs) at the P4 pump are sustained by a serotonin-sensitive calcium conductance. Serotonin enhances calcium entry into the muscle cells and this could lead, as an indirect modulatory effect, to activation of a Ca(2+)-activated K(+) conductance (IK(Ca)), which sustains the following mAP repolarization phase in such a way that further mAPs can be generated early and the frequency consequently increased.

  13. Molecular cloning and functional expression in heterologous mammalian cells of the cDNAs encoding lactate dehydrogenase isozymes A (muscle), B (heart), and C (testis) from man and mouse

    SciTech Connect

    Sakai, I.; Hou, E.W.; Sharief, F.S.; Hiraoka, B.Y.; Takano, T.; Li, S.S.L.

    1987-05-01

    The full-length cDNAs encoding human LHD-A (muscle), human and mouse LDH-B (heart), and mouse LDH-C (testis) isozymes have been isolated and their nucleotide sequences determined. The cDNAs for human LDH-A and mouse LDH-C isozymes were inserted into mammalian expression vectors and were shown to direct the synthesis of functional LDH isozymes in Chinese hamster ovary cells. The exogeneous LDH-A and LDH-C subunits were found to form hybrid LDH tetrameric isozymes with endogeneous LDH-A subunit of CHO cells. The genomic DNA containing LDH cDNA insert and the levels of mRNA expression are being characterized.

  14. Flight Capacity of Bactrocera dorsalis (Diptera: Tephritidae) Adult Females Based on Flight Mill Studies and Flight Muscle Ultrastructure

    PubMed Central

    Chen, Peng; Yuan, Ruiling; Wang, Xiaowei; Xu, Jin

    2015-01-01

    The oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), is considered a major economic threat in many regions worldwide. To better comprehend flight capacity of B. dorsalis and its physiological basis, a computer-monitored flight mill was used to study flight capacity of B. dorsalis adult females of various ages, and the changes of its flight muscle ultrastructures were studied by transmission electron microscopy. The flight capacity (both speed and distance) changed significantly with age of B. dorsalis female adults, peaking at about 15 d; the myofibril diameter of the flight muscle of test insects at 15-d old was the longest, up to 1.56 µm, the sarcomere length at 15-d old was the shortest, averaging at 1.37 µm, volume content of mitochondria of flight muscle at 15-d old reached the peak, it was 32.64%. This study provides the important scientific data for better revealing long-distance movement mechanism of B. dorsalis. PMID:26450591

  15. Impact on nutrition on muscle strength and performance in older adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Muscle strength plays an important role in determining risk for falls, which result in fractures and other injuries. While bone loss has long been recognized as an inevitable consequence of aging, sarcopenia-the gradual loss of skeletal muscle mass and strength that occurs with advancing age-has rec...

  16. Differential adaptations during growth spurt and in young adult rat muscles.

    PubMed

    Barros, K M F T; Manhaes-de-Castro, R; Goubel, F; Canon, F

    2009-01-01

    During the post-weaning growth and maturation period (25/90 days after birth), rat limb muscles are submitted to specific adaptations. Our aim was to characterize the mechanical properties of two muscles that are opposite in terms of fibre-type distribution, the soleus and the extensor digitorum longus (EDL) muscles of male Wistar rats. Results showed a fast-to-slow fibre-type transition in soleus while no modification in fibre-type distribution was observed in EDL. A growth-induced increase in muscle force was observed. Soleus underwent an increase in twitch kinetics, but EDL showed no modification. Resistance to fatigue was higher in 90-day-old soleus but not modified in the EDL. Surprisingly, analysis of maximal shortening velocity showed a decrease in both soleus and EDL. Finally, tension/extension curves indicated a growth-induced increase in series elastic stiffness in the two muscles. These results suggest that during this growth period, skeletal muscles are submitted to differential adaptations. Moreover, whereas adaptation of biomechanical properties observed can be explained partly by an adaptation of fibre profile in soleus, this is not the case for EDL. It is suggested that changes in muscle architecture, which are often disregarded, could explain some variations in mechanical properties, especially when muscles undergo an increase in both mass and length.

  17. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension.

    PubMed

    Aghamohammadzadeh, Reza; Zhang, Ying-Yi; Stephens, Thomas E; Arons, Elena; Zaman, Paula; Polach, Kevin J; Matar, Majed; Yung, Lai-Ming; Yu, Paul B; Bowman, Frederick P; Opotowsky, Alexander R; Waxman, Aaron B; Loscalzo, Joseph; Leopold, Jane A; Maron, Bradley A

    2016-07-01

    Activation of the mammalian target of rapamycin complex 1 (mTORC1) subunit Raptor induces cell growth and is a downstream target of Akt. Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone-Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU-5416/hypoxia-PAH rats and monocrotaline-PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone-Raptor signaling in human PASMCs. Aldosterone (10(-9) to 10(-7) M) increased Akt/mTOR/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor-small interfering RNA or treated with spironolactone/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival in vitro Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine-monomethoxy polyethylene glycol that was formulated with Raptor-small interfering RNA plus spironolactone in vivo, which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH in vivo Up-regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.-Aghamohammadzadeh, R., Zhang, Y.-Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.-M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth

  18. Human slow troponin T (TNNT1) pre-mRNA alternative splicing is an indicator of skeletal muscle response to resistance exercise in older adults.

    PubMed

    Zhang, Tan; Choi, Seung Jun; Wang, Zhong-Min; Birbrair, Alexander; Messi, María L; Jin, Jian-Ping; Marsh, Anthony P; Nicklas, Barbara; Delbono, Osvaldo

    2014-12-01

    Slow skeletal muscle troponin T (TNNT1) pre-messenger RNA alternative splicing (AS) provides transcript diversity and increases the variety of proteins the gene encodes. Here, we identified three major TNNT1 splicing patterns (AS1-3), quantified their expression in the vastus lateralis muscle of older adults, and demonstrated that resistance training modifies their relative abundance; specifically, upregulating AS1 and downregulating AS2 and AS3. In addition, abundance of TNNT1 AS2 correlated negatively with single muscle fiber-specific force after resistance training, while abundance of AS1 correlated negatively with V max. We propose that TNNT1 AS1, AS2 and the AS1/AS2 ratio are potential quantitative biomarkers of skeletal muscle adaptation to resistance training in older adults, and that their profile reflects enhanced single fiber muscle force in the absence of significant increases in fiber cross-sectional area.

  19. Human Slow Troponin T (TNNT1) Pre-mRNA Alternative Splicing Is an Indicator of Skeletal Muscle Response to Resistance Exercise in Older Adults

    PubMed Central

    Zhang, Tan; Choi, Seung Jun; Wang, Zhong-Min; Birbrair, Alexander; Messi, María L.; Jin, Jian-Ping; Marsh, Anthony P.; Nicklas, Barbara

    2014-01-01

    Slow skeletal muscle troponin T (TNNT1) pre-messenger RNA alternative splicing (AS) provides transcript diversity and increases the variety of proteins the gene encodes. Here, we identified three major TNNT1 splicing patterns (AS1–3), quantified their expression in the vastus lateralis muscle of older adults, and demonstrated that resistance training modifies their relative abundance; specifically, upregulating AS1 and downregulating AS2 and AS3. In addition, abundance of TNNT1 AS2 correlated negatively with single muscle fiber–specific force after resistance training, while abundance of AS1 correlated negatively with V max. We propose that TNNT1 AS1, AS2 and the AS1/AS2 ratio are potential quantitative biomarkers of skeletal muscle adaptation to resistance training in older adults, and that their profile reflects enhanced single fiber muscle force in the absence of significant increases in fiber cross-sectional area. PMID:24368775

  20. Effects of Nordic walking on pelvis motion and muscle activities around the hip joints of adults with hip osteoarthritis

    PubMed Central

    Homma, Daisuke; Jigami, Hirofumi; Sato, Naritoshi

    2016-01-01

    [Purpose] Increased compensatory pelvic movement is remarkable in limping patients with hip osteoarthritis (OA). However, a method of improving limping has not been established. The purpose of this study was to identify the effects of two types of Nordic walking by analyzing the pelvic movement and muscle activities of adults with hip OA. [Subjects and Methods] Ten patients with OA of the hip performed Japanese-style Nordic walking (JS NW), European-style Nordic walking (ES NW), and Ordinary walking (OW), and the muscle activities around the hip joint and pelvic movements were analyzed. [Results] The pelvic rotation angle was significantly larger in ES NW than in JS NW. In the stance phase, hip abductor muscle activity was significantly decreased in JS NW compared to both OW and ES NW. In the swing phase, rectus abdominis muscle activity was significantly increased in both JS NW and ES NW compared to OW and lumbar erector spinae activity was significantly lower in JS NW than in OW. [Conclusion] JS NW style may reduce the compensatory pelvic rotation in patients with hip OA. JS NW might be better for joint protection and prevention of secondary disorders of the hip in OA patients. PMID:27190455

  1. Small Fractions of Muscular Dystrophy Embryonic Stem Cells Yield Severe Cardiac and Skeletal Muscle Defects in Adult Mouse Chimeras.

    PubMed

    Gonzalez, J Patrick; Kyrychenko, Sergii; Kyrychenko, Viktoriia; Schneider, Joel S; Granier, Celine J; Himelman, Eric; Lahey, Kevin C; Zhao, Qingshi; Yehia, Ghassan; Tao, Yuan-Xiang; Bhaumik, Mantu; Shirokova, Natalia; Fraidenraich, Diego

    2017-03-01

    Duchenne muscular dystrophy (DMD) is characterized by the loss of the protein dystrophin, leading to muscle fragility, progressive weakening, and susceptibility to mechanical stress. Although dystrophin-negative mdx mouse models have classically been used to study DMD, phenotypes appear mild compared to patients. As a result, characterization of muscle pathology, especially in the heart, has proven difficult. We report that injection of mdx embryonic stem cells (ESCs) into Wild Type blastocysts produces adult mouse chimeras with severe DMD phenotypes in the heart and skeletal muscle. Inflammation, regeneration and fibrosis are observed at the whole organ level, both in dystrophin-negative and dystrophin-positive portions of the chimeric tissues. Skeletal and cardiac muscle function are also decreased to mdx levels. In contrast to mdx heterozygous carriers, which show no significant phenotypes, these effects are even observed in chimeras with low levels of mdx ESC incorporation (10%-30%). Chimeric mice lack typical compensatory utrophin upregulation, and show pathological remodeling of Connexin-43. In addition, dystrophin-negative and dystrophin-positive isolated cardiomyocytes show augmented calcium response to mechanical stress, similar to mdx cells. These global effects highlight a novel role of mdx ESCs in triggering muscular dystrophy even when only low amounts are present. Stem Cells 2017;35:597-610.

  2. The human tongue slows down to speak: muscle fibers of the human tongue.

    PubMed

    Sanders, Ira; Mu, Liancai; Amirali, Asif; Su, Hungxi; Sobotka, Stanislaw

    2013-10-01

    Little is known about the specializations of human tongue muscles. In this study, myofibrillar adenosine triphosphatase (mATPase) histochemical staining was used to study the percentage and distribution of slow twitch muscle fibers (slow MFs) within tongue muscles of four neurologically normal human adults and specimens from a 2-year-old human, a newborn human, an adult with idiopathic Parkinson's disease (IPD), and a macaque monkey. The average percentage of slow MFs in adult and the 2-year-old muscle specimens was 54%, the IPD was 45%, while the neonatal human (32%) and macaque monkey (28%) had markedly fewer slow MFs. In contrast, the tongue muscles of the rat and cat have been reported to have no slow MFs. There was a marked spatial gradient in the distribution of slow MFs with the highest percentages found medially and posteriorly. Normal adult tongue muscles were found to have a variety of uniquely specialized features including MF-type grouping (usually found in neuromuscular disorders), large amounts of loose connective tissue, and short branching MFs. In summary, normal adult human tongue muscles have by far the highest proportion of slow MFs of any mammalian tongue studied to date. Moreover, adult human tongue muscles have multiple unique anatomic features. As the tongue shape changes that are seen during speech articulation are unique to humans, we hypothesize that the large proportion of slow MFs and the anatomical specializations observed in the adult human tongue have evolved to perform these movements.

  3. Muscle repair and regeneration: stem cells, scaffolds, and the contributions of skeletal muscle to amphibian limb regeneration.

    PubMed

    Milner, Derek J; Cameron, Jo Ann

    2013-01-01

    Skeletal muscle possesses a robust innate capability for repair of tissue damage. Natural repair of muscle damage is a stepwise process that requires the coordinated activity of a number of cell types, including infiltrating macrophages, resident myogenic and non-myogenic stem cells, and connective tissue fibroblasts. Despite the proficiency of this intrinsic repair capability, severe injuries that result in significant loss of muscle tissue overwhelm the innate repair process and require intervention if muscle function is to be restored. Recent advances in stem cell biology, regenerative medicine, and materials science have led to attempts at developing tissue engineering-based methods for repairing severe muscle defects. Muscle tissue also plays a role in the ability of tailed amphibians to regenerate amputated limbs through epimorphic regeneration. Muscle contributes adult stem cells to the amphibian regeneration blastema, but it can also contribute blastemal cells through the dedifferentiation of multinucleate myofibers into mononuclear precursors. This fascinating plasticity and its contributions to limb regeneration have prompted researchers to investigate the potential for mammalian muscle to undergo dedifferentiation. Several works have shown that mammalian myotubes can be fragmented into mononuclear cells and induced to re-enter the cell cycle, but mature myofibers are resistant to fragmentation. However, recent works suggest that there may be a path to inducing fragmentation of mature myofibers into proliferative multipotent cells with the potential for use in muscle tissue engineering and regenerative therapies.

  4. Cellular organization of the central canal ependymal zone, a niche of latent neural stem cells in the adult mammalian spinal cord.

    PubMed

    Hamilton, L K; Truong, M K V; Bednarczyk, M R; Aumont, A; Fernandes, K J L

    2009-12-15

    A stem cell's microenvironment, or "niche," is a critical regulator of its behaviour. In the adult mammalian spinal cord, central canal ependymal cells possess latent neural stem cell properties, but the ependymal cell niche has not yet been described. Here, we identify important similarities and differences between the central canal ependymal zone and the forebrain subventricular zone (SVZ), a well-characterized niche of neural stem cells. First, direct immunohistochemical comparison of the spinal cord ependymal zone and the forebrain SVZ revealed distinct patterns of neural precursor marker expression. In particular, ependymal cells in the spinal cord were found to be bordered by a previously uncharacterized sub-ependymal layer, which is relatively less elaborate than that of the SVZ and comprised of small numbers of astrocytes, oligodendrocyte progenitors and neurons. Cell proliferation surrounding the central canal occurs in close association with blood vessels, but unlike in the SVZ, involves mainly ependymal rather than sub-ependymal cells. These proliferating ependymal cells typically self-renew rather than produce transit-amplifying progenitors, as they generate doublets of progeny that remain within the ependymal layer and show no evidence of a lineage relationship to sub-ependymal cells. Interestingly, the dorsal pole of the central canal was found to possess a sub-population of tanycyte-like cells that express markers of both ependymal cells and neural precursors, and their presence correlates with higher numbers of dorsally proliferating ependymal cells. Together, these data identify key features of the spinal cord ependymal cell niche, and suggest that dorsal ependymal cells possess the potential for stem cell activity. This work provides a foundation for future studies aimed at understanding ependymal cell regulation under normal and pathological conditions.

  5. Rapid evolution of larval life history, adult immune function and flight muscles in a poleward-moving damselfly.

    PubMed

    Therry, L; Nilsson-Örtman, V; Bonte, D; Stoks, R

    2014-01-01

    Although a growing number of studies have documented the evolution of adult dispersal-related traits at the range edge of poleward-expanding species, we know little about evolutionary changes in immune function or traits expressed by nondispersing larvae. We investigated differentiation in larval (growth and development) and adult traits (immune function and flight-related traits) between replicated core and edge populations of the poleward-moving damselfly Coenagrion scitulum. These traits were measured on individuals reared in a common garden experiment at two different food levels, as allocation trade-offs may be easier to detect under energy shortage. Edge individuals had a faster larval life history (growth and development rates), a higher adult immune function and a nearly significant higher relative flight muscle mass. Most of the differentiation between core and edge populations remained and edge populations had a higher relative flight muscle mass when corrected for latitude-specific thermal regimes, and hence could likely be attributed to the range expansion process per se. We here for the first time document a higher immune function in individuals at the expansion front of a poleward-expanding species and documented the rarely investigated evolution of faster life histories during range expansion. The rapid multivariate evolution in these ecological relevant traits between edge and core populations is expected to translate into changed ecological interactions and therefore has the potential to generate novel eco-evolutionary dynamics at the expansion front.

  6. Association of force steadiness of plantar flexor muscles and postural sway during quiet standing by young adults.

    PubMed

    Oshita, Kazushige; Yano, Sumio

    2012-08-01

    This study was conducted to assess the relations of force fluctuations during isometric plantar-flexion and postural sway during quiet standing. Twelve healthy men (M age = 21 yr., SD = 1) performed unilateral plantar flexion measured by a strain gauge force transducer. Participants performed force-matching tasks; sustained plantar flexion for 20 sec. at levels corresponding to 10% and 20% of maximum voluntary contraction with the visual feedback. Also, participants were asked to stand quietly with their eyes open, and then the center of mass displacement and velocity in the anteroposterior were measured. In analysis, postural sway was associated with force fluctuation at only 10% of maximum voluntary contraction. The statistically significant correlation between variables was found only at corresponding contraction intensities for plantar-flexor muscles. From this one may infer neural strategies in plantar-flexor muscles during quiet standing may be characteristics similar to those controlling the plantar-flexion force in young adults.

  7. Shoulder muscle fatigue development in young and older female adults during a repetitive manual task.

    PubMed

    Qin, Jin; Lin, Jia-Hua; Buchholz, Bryan; Xu, Xu

    2014-01-01

    Age may modify the association between occupational physical demand and muscle loading, and ultimately increase the risk of musculoskeletal disorders. The goal of this study was to investigate age-related differences in shoulder muscle fatigue development during a repetitive manual task. Twenty participants in two age groups completed an 80-minute simulated low-intensity assembly task. Electromyographic (EMG) manifestation of muscle fatigue was observed in the upper trapezius, deltoid and infraspinatus muscles in both age groups, and coincided with an increase in the subjective ratings of perceived exertions. Compared with the younger group, older group showed a more monotonic decrease in EMG power frequency in the upper trapezius and deltoid muscles. However, the age-related difference in EMG amplitude was less consistent. Relative rest time of the upper trapezius muscle in the older group was less than the young group throughout the task. The observed patterns of EMG measures suggest that older participants may have disadvantages in fatigue resistance in the upper trapezius and posterior deltoid muscles during the simulated repetitive manual task.

  8. Dystrophy of the diaphragmatic muscles in adult Meuse-Rhine-Yssel cattle: electromyographical and histological findings.

    PubMed

    Goedegebuure, S A; Hartman, W; Hoebe, H P

    1983-01-01

    Electromyographic investigation of diaphragmatic muscles of Meuse-Rhine-Yssel cattle revealed a significant decreased duration of action potentials, while the number of polyphasic potentials was increased in four of seven cows. Histologically, the diaphragmatic muscles in all cows were affected severely, as characterized by variation in size of individual fibers, abundant vacuolar and hyaline degeneration with occasional fragmentation and phagocytosis, fiber splitting, apparent increase in internal nuclei, vesicular nuclei, chains of central nuclei, absence of regeneration, and proliferation of endomysial and perimysial connective tissue. Core-like structures seemed to be a hallmark of the disease. The intercostal muscles in all cows had core-like structures and some variation in fiber size; degenerative lesions did occur, but were less severe than in diaphragmatic muscles. In other skeletal muscles and cardiac muscles, core-like structures were present predominantly, indicating a generalized muscle disorder. No lesions were detected in the peripheral or central nervous systems. The muscular alterations were classified as a progressive muscular dystrophy, with a suspicion of hereditary transmission. This dystrophy may be an important animal model.

  9. Erythropoietin Does Not Enhance Skeletal Muscle Protein Synthesis Following Exercise in Young and Older Adults

    PubMed Central

    Lamon, Séverine; Zacharewicz, Evelyn; Arentson-Lantz, Emily; Gatta, Paul A. Della; Ghobrial, Lobna; Gerlinger-Romero, Frederico; Garnham, Andrew; Paddon-Jones, Douglas; Russell, Aaron P.

    2016-01-01

    Purpose: Erythropoietin (EPO) is a renal cytokine that is primarily involved in hematopoiesis while also playing a role in non-hematopoietic tissues expressing the EPO-receptor (EPOR). The EPOR is present in human skeletal muscle. In mouse skeletal muscle, EPO stimulation can activate the AKT serine/threonine kinase 1 (AKT) signaling pathway, the main positive regulator of muscle protein synthesis. We hypothesized that a single intravenous EPO injection combined with acute resistance exercise would have a synergistic effect on skeletal muscle protein synthesis via activation of the AKT pathway. Methods: Ten young (24.2 ± 0.9 years) and 10 older (66.6 ± 1.1 years) healthy subjects received a primed, constant infusion of [ring-13C6] L-phenylalanine and a single injection of 10,000 IU epoetin-beta or placebo in a double-blind randomized, cross-over design. 2 h after the injection, the subjects completed an acute bout of leg extension resistance exercise to stimulate skeletal muscle protein synthesis. Results: Significant interaction effects in the phosphorylation levels of the members of the AKT signaling pathway indicated a differential activation of protein synthesis signaling in older subjects when compared to young subjects. However, EPO offered no synergistic effect on vastus lateralis mixed muscle protein synthesis rate in young or older subjects. Conclusions: Despite its ability to activate the AKT pathway in skeletal muscle, an acute EPO injection had no additive or synergistic effect on the exercise-induced activation of muscle protein synthesis or muscle protein synthesis signaling pathways. PMID:27458387

  10. Obstructive sleep apnea - adults

    MedlinePlus

    Sleep apnea - obstructive - adults; Apnea - obstructive sleep apnea syndrome - adults; Sleep-disordered breathing - adults; OSA - adults ... When you sleep, all of the muscles in your body become more relaxed. This includes the muscles that help keep your ...

  11. The Interscutularis Muscle Connectome

    PubMed Central

    Lu, Ju; Tapia, Juan Carlos; White, Olivia L; Lichtman, Jeff W

    2009-01-01

    The complete connectional map (connectome) of a neural circuit is essential for understanding its structure and function. Such maps have only been obtained in Caenorhabditis elegans. As an attempt at solving mammalian circuits, we reconstructed the connectomes of six interscutularis muscles from adult transgenic mice expressing fluorescent proteins in all motor axons. The reconstruction revealed several organizational principles of the neuromuscular circuit. First, the connectomes demonstrate the anatomical basis of the graded tensions in the size principle. Second, they reveal a robust quantitative relationship between axonal caliber, length, and synapse number. Third, they permit a direct comparison of the same neuron on the left and right sides of the same vertebrate animal, and reveal significant structural variations among such neurons, which contrast with the stereotypy of identified neurons in invertebrates. Finally, the wiring length of axons is often longer than necessary, contrary to the widely held view that neural wiring length should be minimized. These results show that mammalian muscle function is implemented with a variety of wiring diagrams that share certain global features but differ substantially in anatomical form. This variability may arise from the dominant role of synaptic competition in establishing the final circuit. PMID:19209956

  12. When is a neck lump not a neck lump? Initial presentation of a solitary sternocleidomastoid muscle in an adult.

    PubMed

    Kumar, Sonia; Jervis, Suzie; Uppal, Harpreet

    2014-01-01

    A 70-year-old woman was referred to us for evaluation of a presumed left-sided neck mass. The referral was based on the visual appearance of subtle neck asymmetry. The patient reported no ENT symptoms. Clinical examination and ultrasonography identified no pathology, but computed tomography revealed that the asymmetry was present because the patient's right sternocleidomastoid muscle (SCM) was absent. The SCM on the left side was normal. Congenital absence of an SCM is uncommon, and to the best of our knowledge, an initial presentation in an adult has not been previously reported in the literature.

  13. Adiposity attenuates muscle quality and the adaptive response to resistance exercise in non-obese, healthy adults

    PubMed Central

    Peterson, MD; Liu, D; Gordish-Dressman, H; Hubal, MJ; Pistilli, E; Angelopoulos, TJ; Clarkson, PM; Moyna, NM; Pescatello, LS; Seip, RL; Visich, PS; Zoeller, RF; Thompson, PD; Devaney, JM; Hoffman, EP; Gordon, PM

    2014-01-01

    Background Emerging data have revealed a negative association between adiposity and muscle quality (MQ). There is a lack of research to examine this interaction among young, healthy individuals, and to evaluate the contribution of adiposity to adaptation after resistance exercise (RE). Objective The purpose of this investigation was to examine the influence of subcutaneous adipose tissue (SAT) on muscle function among non-obese individuals before and after RE. Design Analyses included 634 non-obese (body mass index < 30 kg m−2) subjects (253 males, 381 females; age = 23.3±5.2 years). SAT and muscle mass (magnetic resonance imaging-derived SAT and biceps muscle volume), isometric and dynamic biceps strength, and MQ (strength/muscle volume), were analyzed at baseline and after 12 weeks of unilateral RE. Results At baseline, SAT was independently associated with lower MQ for males (β = −0.55; P < 0.01) and females (β = −0.45; P < 0.01), controlling for body mass and age. Adaptation to RE revealed a significant negative association between SAT and changes for strength capacity (β = −0.13; p − 0.03) and MQ (β = −0.14; P < 0.01) among males. No attenuation was identified among females. Post-intervention SAT remained a negative predictor of MQ for males and females (β = − 0.47; P < 0.01). Conclusions The findings reveal that SAT is a negative predictor of MQ among non-obese, healthy adults, and that after 12 weeks of progressive RE this association was not ameliorated. Data suggest that SAT exerts a weak, negative influence on the adaptive response to strength and MQ among males. PMID:21139562

  14. Degenerin channel activation causes caspase‐mediated protein degradation and mitochondrial dysfunction in adult C. elegans muscle

    PubMed Central

    Gaffney, Christopher J.; Shephard, Freya; Chu, Jeff; Baillie, David L.; Rose, Ann; Constantin‐Teodosiu, Dumitru; Greenhaff, Paul L.

    2015-01-01

    Abstract Background Declines in skeletal muscle structure and function are found in various clinical populations, but the intramuscular proteolytic pathways that govern declines in these individuals remain relatively poorly understood. The nematode Caenorhabditis elegans has been developed into a model for identifying and understanding these pathways. Recently, it was reported that UNC‐105/degenerin channel activation produced muscle protein degradation via an unknown mechanism. Methods Generation of transgenic and double mutant C. elegans, RNAi, and drug treatments were utilized to assess molecular events governing protein degradation. Western blots were used to measure protein content. Cationic dyes and adenosine triphosphate (ATP) production assays were utilized to measure mitochondrial function. Results unc‐105 gain‐of‐function mutants display aberrant muscle protein degradation and a movement defect; both are reduced in intragenic revertants and in let‐2 mutants that gate the hyperactive UNC‐105 channel. Degradation is not suppressed by interventions suppressing proteasome‐mediated, autophagy‐mediated, or calpain‐mediated degradation nor by suppressors of degenerin‐induced neurodegeneration. Protein degradation, but not the movement defect, is decreased by treatment with caspase inhibitors or RNAi against ced‐3 or ced‐4. Adult unc‐105 muscles display a time‐dependent fragmentation of the mitochondrial reticulum that is associated with impaired mitochondrial membrane potential and that correlates with decreased rates of maximal ATP production. Reduced levels of CED‐4, which is sufficient to activate CED‐3 in vitro, are observed in unc‐105 mitochondrial isolations. Conclusions Constitutive cationic influx into muscle appears to cause caspase degradation of cytosolic proteins as the result of mitochondrial dysfunction, which may be relevant to ageing and sarcopenia. PMID:27493871

  15. The Effect of Branched Chain Amino Acids on Skeletal Muscle Mitochondrial Function in Young and Elderly Adults

    PubMed Central

    Tatpati, Laura L.; Irving, Brian A.; Tom, Andrea; Bigelow, Maureen L.; Klaus, Katherine; Short, Kevin R.; Nair, K. Sreekumaran

    2010-01-01

    Context: A reduction in maximal mitochondrial ATP production rate (MAPR) and mitochondrial DNA (mtDNA) abundance occurs with age in association with muscle weakness and reduced endurance in elderly people. Branched chain amino acids (BCAA) have been extensively used to improve physical performance. Objective: The objective was to determine whether an 8-h infusion of BCAA enhances MAPR equally in healthy young and elderly adults. Methods: Using a crossover study design, we compared the effect BCAA vs. saline infusion in 12 young (23.0 ± 0.8 yr) and 12 elderly (70.7 ± 1.1 yr) participants matched for sex and body mass index. Skeletal muscle MAPR and mtDNA abundance were measured in muscle biopsy samples obtained before and at the end of the 8-h infusion. Results: In young participants, MAPR with the substrates glutamate plus malate (supplying electrons to complex I) and succinate plus rotenone (complex II) increased in response to BCAA infusion, relative to a decline in MAPR in response to the saline infusion. In contrast, MAPR was unaffected by BCAA infusion in the elderly participants. Moreover, mtDNA abundance was lower in the elderly compared with the young participants but was unaffected by the BCAA infusion. Insulin and C-peptide concentrations declined over time during the saline infusion, but these declines were prevented by the BCAA infusion. Conclusions: BCAA increased skeletal muscle MAPR in the young participants in comparison with saline, but this effect was not seen in the elderly participants indicating, that unlike in the young, BCAA does not increase muscle mitochondrial function in the elderly. PMID:20022987

  16. The influence of occlusion on jaw and neck muscle activity: a surface EMG study in healthy young adults.

    PubMed

    Ferrario, V F; Tartaglia, G M; Galletta, A; Grassi, G P; Sforza, C

    2006-05-01

    The electromyographic (EMG) characteristics of masseter, temporalis and sternocleidomastoid (SCM) muscles during maximum voluntary teeth clench were assessed in 27 male and 35 female healthy young adults. Subjects were divided into two groups: (i) 'complete' Angle Class I (bilateral, symmetric canine and molar Class I relationships), and (ii) 'partial' Angle Class I (one to three canine/molar Class I relationships, the remaining relationships were Class II or Class III). On average, standardized muscular symmetry ranged 80.7-87.9%. During maximum voluntary teeth clench, average co-contraction of SCM muscle was 13.7-23.5% of its maximum contraction. On average, all torque coefficients (potential lateral displacing component) were >90%, while all antero-posterior coefficients (relative activities of masseter and temporalis muscles) were >85%. The average integrated areas of the masseter and temporalis EMG potentials over time ranged 87.4-106.8 muV/muV s%. Standardized contractile muscular activities did not differ between 'complete' and 'partial' Angle Class I, and between sexes (two-way analysis of variance). A trend toward a larger intragroup variability in EMG indices was observed in the subjects with 'partial' Angle Class I than in those with 'complete' Angle Class I (significant difference for the temporalis muscle symmetry, P = 0.013, analysis of variance). In conclusion, the presence of a complete or partial Angle occlusal Class I did not seem to influence the standardized contractile activities of masseter, temporalis and SCM muscles during a maximum voluntary clench. Subjects with a 'complete' Angle Class I were somewhat a more homogenous group than subjects with 'partial' Angle Class I.

  17. Impact of fasting on the rhythmic expression of myogenic and metabolic factors in skeletal muscle of adult mice.

    PubMed

    Shavlakadze, T; Anwari, T; Soffe, Z; Cozens, G; Mark, P J; Gondro, C; Grounds, M D

    2013-07-01

    Circadian rhythms and metabolism are tightly integrated, and rhythmic expression of metabolic factors is common in homeostatic processes. We measured the temporal changes in the expression of myogenic regulatory factors and expression and activity level of molecules involved in protein metabolism in skeletal muscles and livers in mice and examined the impact of fasting. Tissues were collected over 24 h (at zeitgeber times ZT1, ZT5, ZT9, ZT13, ZT17, ZT21, and ZT1 the following day) from adult male C57Bl/6J mice that had been either freely fed or fasted for 24 h. In skeletal muscle, there was a robust rise in the mRNA expression of the myogenic regulatory factors MyoD and myogenin during dark hours which was strongly suppressed by fasting. Circadian pattern was observed for mRNA of MuRF1, Akt1, and ribosomal protein S6 in muscles in fed and fasted mice and for Fbxo32 in fed mice. Activity (phosphorylation) levels of Akt(Ser473) displayed temporal regulation in fasted (but not fed) mice and were high at ZT9. Fasting caused significant reductions in phosphorylation for both Akt and S6 in muscles, indicative of inactivation. Hepatic phosphorylated Akt(Ser473) and S6(Ser235/236) proteins did not exhibit daily rhythms. Fasting significantly reduced hepatic Akt(473) phosphorylation compared with fed levels, although (unlike in muscle) it did not affect S6(Ser235/236) phosphorylation. This in vivo circadian study addresses for the first time the signaling activities of key molecules related to protein turnover and their possible cross-regulation of expression of genes related to protein degradation.

  18. Impaired voluntary neuromuscular activation limits muscle power in mobility-limited older adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background. Age-related alterations of neuromuscular activation may contribute to deficits in muscle power and mobility function. This study assesses whether impaired activation of the agonist quadriceps and antagonist hamstrings, including amplitude- and velocity-dependent characteristics of activa...

  19. Eccentric Torque-Producing Capacity is Influenced by Muscle Length in Older Healthy Adults.

    PubMed

    Melo, Ruth C; Takahashi, Anielle C M; Quitério, Robison J; Salvini, Tânia F; Catai, Aparecida M

    2016-01-01

    Considering the importance of muscle strength to functional capacity in the elderly, the study investigated the effects of age on isokinetic performance and torque production as a function of muscle length. Eleven younger (24.2 ± 2.9 years) and 16 older men (62.7 ± 2.5 years) were subjected to concentric and eccentric isokinetic knee extension/flexion at 60 and 120° · s(-1) through a functional range of motion. The older group presented lower peak torque (in newton-meters) than the young group for both isokinetic contraction types (age effect, p < 0.001). Peak torque deficits in the older group were near 30 and 29% for concentric and eccentric contraction, respectively. Concentric peak torque was lower at 120° · s(-1) than at 60° · s(-1) for both groups (angular velocity effect, p < 0.001). Eccentric knee extension torque was the only exercise tested that showed an interaction effect between age and muscle length (p < 0.001), which suggested different torque responses to the muscle length between groups. Compared with the young group, the eccentric knee extension torque was 22-56% lower in the older group, with the deficits being lower in the shortened muscle length (22-27%) and higher (33-56%) in the stretched muscle length. In older men, the production of eccentric knee strength seems to be dependent on the muscle length. At more stretched positions, older subjects lose the capacity to generate eccentric knee extension torque. More studies are needed to assess the mechanisms involved in eccentric strength preservation with aging and its relationship with muscle length.

  20. Ultrasound estimates of muscle quality in older adults: reliability and comparison of Photoshop and ImageJ for the grayscale analysis of muscle echogenicity

    PubMed Central

    Seamon, Bryant A.; Teixeira, Carla; Ismail, Catheeja

    2016-01-01

    Background. Quantitative diagnostic ultrasound imaging has been proposed as a method of estimating muscle quality using measures of echogenicity. The Rectangular Marquee Tool (RMT) and the Free Hand Tool (FHT) are two types of editing features used in Photoshop and ImageJ for determining a region of interest (ROI) within an ultrasound image. The primary objective of this study is to determine the intrarater and interrater reliability of Photoshop and ImageJ for the estimate of muscle tissue echogenicity in older adults via grayscale histogram analysis. The secondary objective is to compare the mean grayscale values obtained using both the RMT and FHT methods across both image analysis platforms. Methods. This cross-sectional observational study features 18 community-dwelling men (age = 61.5 ± 2.32 years). Longitudinal views of the rectus femoris were captured using B-mode ultrasound. The ROI for each scan was selected by 2 examiners using the RMT and FHT methods from each software program. Their reliability is assessed using intraclass correlation coefficients (ICCs) and the standard error of the measurement (SEM). Measurement agreement for these values is depicted using Bland-Altman plots. A paired t-test is used to determine mean differences in echogenicity expressed as grayscale values using the RMT and FHT methods to select the post-image acquisition ROI. The degree of association among ROI selection methods and image analysis platforms is analyzed using the coefficient of determination (R2). Results. The raters demonstrated excellent intrarater and interrater reliability using the RMT and FHT methods across both platforms (lower bound 95% CI ICC = .97–.99, p < .001). Mean differences between the echogenicity estimates obtained with the RMT and FHT methods was .87 grayscale levels (95% CI [.54–1.21], p < .0001) using data obtained with both programs. The SEM for Photoshop was .97 and 1.05 grayscale levels when using the RMT and FHT ROI selection methods

  1. Ultrasound estimates of muscle quality in older adults: reliability and comparison of Photoshop and ImageJ for the grayscale analysis of muscle echogenicity.

    PubMed

    Harris-Love, Michael O; Seamon, Bryant A; Teixeira, Carla; Ismail, Catheeja

    2016-01-01

    Background. Quantitative diagnostic ultrasound imaging has been proposed as a method of estimating muscle quality using measures of echogenicity. The Rectangular Marquee Tool (RMT) and the Free Hand Tool (FHT) are two types of editing features used in Photoshop and ImageJ for determining a region of interest (ROI) within an ultrasound image. The primary objective of this study is to determine the intrarater and interrater reliability of Photoshop and ImageJ for the estimate of muscle tissue echogenicity in older adults via grayscale histogram analysis. The secondary objective is to compare the mean grayscale values obtained using both the RMT and FHT methods across both image analysis platforms. Methods. This cross-sectional observational study features 18 community-dwelling men (age = 61.5 ± 2.32 years). Longitudinal views of the rectus femoris were captured using B-mode ultrasound. The ROI for each scan was selected by 2 examiners using the RMT and FHT methods from each software program. Their reliability is assessed using intraclass correlation coefficients (ICCs) and the standard error of the measurement (SEM). Measurement agreement for these values is depicted using Bland-Altman plots. A paired t-test is used to determine mean differences in echogenicity expressed as grayscale values using the RMT and FHT methods to select the post-image acquisition ROI. The degree of association among ROI selection methods and image analysis platforms is analyzed using the coefficient of determination (R (2)). Results. The raters demonstrated excellent intrarater and interrater reliability using the RMT and FHT methods across both platforms (lower bound 95% CI ICC = .97-.99, p < .001). Mean differences between the echogenicity estimates obtained with the RMT and FHT methods was .87 grayscale levels (95% CI [.54-1.21], p < .0001) using data obtained with both programs. The SEM for Photoshop was .97 and 1.05 grayscale levels when using the RMT and FHT ROI selection methods

  2. MicroRNA deep sequencing in two adult stem cell populations identifies miR-501 as a novel regulator of myosin heavy chain during muscle regeneration

    PubMed Central

    Mizbani, Amir; Luca, Edlira; Rushing, Elisabeth J.

    2016-01-01

    MicroRNAs (miRNAs) are important regulators of skeletal muscle regeneration, but the underlying mechanisms are still incompletely understood. Here, comparative miRNA sequencing analysis of myogenic progenitor cells (MPs) and non-myogenic fibroblast-adipocyte progenitors (FAPs) during cardiotoxin (CTX)-induced muscle injury uncovered miR-501 as a novel muscle-specific miRNA. miR-501 is an intronic miRNA and its expression levels in MPs correlated with its host gene, chloride channel, voltage-sensitive 5 (Clcn5). Pharmacological inhibition of miR-501 dramatically blunted the induction of embryonic myosin heavy chain (MYH3) and, to a lesser extent, adult myosin isoforms during muscle regeneration, and promoted small-diameter neofibers. An unbiased target identification approach in primary myoblasts validated gigaxonin as a target of miR-501 that mimicked the effect of miR-501 inhibition on MYH3 expression. In the mdx mouse model, which models a pathological disease state, not only was miR-501 induced in regenerating skeletal muscle, but also its serum levels were increased, which correlated with the disease state of the animals. Our results suggest that miR-501 plays a key role in adult muscle regeneration and might serve as a novel serum biomarker for the activation of adult muscle stem cells. PMID:27707793

  3. Basic fibroblast growth factor has a differential effect on MyoD conversion of cultured aortic smooth muscle cells from newborn and adult rats.

    PubMed Central

    van Neck, J. W.; Medina, J. J.; Onnekink, C.; van der Ven, P. F.; Bloemers, H. P.; Schwartz, S. M.

    1993-01-01

    MyoD is a master regulatory gene for myogenesis that also converts many mesoderm-derived cells into the skeletal muscle phenotype. Rat aortic smooth muscle cells do not contain MyoD homologous mRNA. However, expression of an exogenously supplied MyoD gene in aortic smooth muscle cells cultured from newborn and adult animals converts these cells to elongated myoblasts and myotubes expressing the skeletal muscle genes for titin, nebulin, myosin, and skeletal alpha-actin. The presence of basic fibroblast growth factor during growth and serum starvation completely inhibits MyoD-mediated conversion in cultures of newborn smooth muscle cells. However, in smooth muscle cell cultures derived from adult rats the presence of fibroblast growth factor increases the conversion frequency. The differential response of exogenous MyoD suggests that the two morphological types of aortic smooth muscle cells, one typical for the newborn rat, the other for the adult rat, represent two distinctive states of differentiation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:8391216

  4. Ascaridole-less infusions of Chenopodium ambrosioides contain a nematocide(s) that is(are) not toxic to mammalian smooth muscle.

    PubMed

    MacDonald, D; VanCrey, K; Harrison, P; Rangachari, P K; Rosenfeld, J; Warren, C; Sorger, G

    2004-06-01

    Infusions of Chenopodium ambrosioides (L.) have been used for centuries in the Americas as a popular remedy against intestinal worm infections. The essential oil of Chenopodium ambrosioides contains high levels of ascaridole, which is a potent anthelmintic, but which has also been responsible for human fatalities, leading to its disuse. Almost 90% of the nematocidal activity of Chenopodium ambrosioides infusions was due to a hydrophilic component different from ascaridole. Synthetic ascaridole and the ascaridole from infusions, extracted into hexane, caused a reduction of carbachol-induced contractions in rat gastrointestinal smooth muscle at concentrations required to kill Caenorhabditis elegans (L.). The herbal infusion and the ascaridole-free hexane-extracted aqueous residue of the above infusion, at nematocidal concentrations, had no detectable effect on smooth muscle contraction in the above system. It would appear that the traditional form of usage of Chenopodium ambrosioides infusions as a vermifuge is safer than the use of the herb's essential oil.

  5. A case of adult-onset reducing body myopathy presenting a novel clinical feature, asymmetrical involvement of the sternocleidomastoid and trapezius muscles.

    PubMed

    Fujii, Takayuki; Hayashi, Shintaro; Kawamura, Nobutoshi; Higuchi, Masa-Aki; Tsugawa, Jun; Ohyagi, Yasumasa; Hayashi, Yukiko K; Nishino, Ichizo; Kira, Jun-Ichi

    2014-08-15

    We herein report a 32-year-old woman with adult-onset reducing body myopathy (RBM) who had a mutation in the four-and-a-half LIM domain 1 gene (FHL1) and showed a marked asymmetrical involvement of sternocleidomastoid and trapezius muscles. At 30 years of age she noticed bilateral foot drop, and over the next two years developed difficulty raising her right arm. At 32 years of age she was admitted to our hospital for a diagnostic evaluation. Neurological examination showed moderate weakness and atrophy of her right sternocleidomastoid muscle, right trapezius muscle, and bilateral upper proximal muscles. There were severe weakness and atrophy of her bilateral tibialis anterior muscles. Her deep tendon reflexes were hypoactive in her upper extremities. Her serum creatine kinase level was mildly increased. Muscle biopsy specimens from the left tibialis anterior muscle revealed marked variation in fiber size, some necrotic or regenerating fibers, and reducing bodies. Gene analysis of FHL1 demonstrated a mutation: a heterozygous missense mutation of c.377G>A (p. C126T) in FHL1. Compared with previous adult-onset RBM cases harboring mutations in FHL1, our case was characterized by asymmetrical atrophy of the sternocleidomastoid and trapezius muscles.

  6. Muscle function is associated with future patient-reported outcomes in young adults with ACL injury

    PubMed Central

    Flosadottir, Vala; Roos, Ewa M; Ageberg, Eva

    2016-01-01

    Background/aim Consequences of an anterior cruciate ligament (ACL) injury include worse patient-reported outcomes (PROs) and a decrease in activity level. Muscle function can be improved by targeted exercise. Our aims were to investigate cross-sectional and longitudinal associations among lower extremity muscle function and PROs after ACL injury. Methods Fifty-four participants (15 women, mean 30 years) with ACL injury or reconstruction, from the Knee Anterior Cruciate Ligament, Nonsurgical versus Surgical Treatment (KANON) trial (ISRCTN84752559), were assessed with hop performance, muscle power and postural orientation 3 years (SD 0.85) after ACL injury. PROs at 3 and 5 years after injury included Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales Function in sport and recreation (KOOS Sport/rec) and Knee-related Quality of life (KOOS QoL), KOOS item Q3 (KOOS Q3), Tegner Activity Scale and Activity Rating Scale (ARS). Partial Spearman's rank-order correlation was used to analyse correlations between muscle function and PROs, controlling for gender and treatment. Results Numerous cross-sectional correlations were observed between muscle function and PROs (rsp≈0.3–0.5, p≤0.045). Worse hop performance and worse postural orientation were associated with worse KOOS scores 2 years later (rsp≥0.280, p≤0.045). Worse muscle power was associated with lower future ARS scores (rsp=0.281, p=0.044). Conclusions The moderate associations suggest that improving muscle function during rehabilitation could improve present and future PROs. PMID:27900196

  7. Taurine drinking attenuates the burden of intestinal adult worms and muscle larvae in mice with Trichinella spiralis infection.

    PubMed

    Yu, Yan-Rong; Liu, Xi-Cheng; Zhang, Jin-Sheng; Ji, Chao-Yue; Qi, Yong-Fen

    2013-10-01

    The parasitic nematode Trichinella spiralis can cause trichinellosis, which leads to pathological processes in the intestine and muscle. The intestinal invasion determines the development, subsequent course, and consequences of the disease. Gastrointestinal nematode infection, including with T. spiralis, is accompanied by a rapid and reversible expansion of mucosal mast cell and goblet cell in the intestinal epithelium, which play important roles in the host immune response to parasite and worm expulsion from the intestine. Taurine and its derivatives have anti-infection and anti-inflammatory properties. We investigated whether taurine supplementation in mice could influence the development and pathological processes of infection with T. spiralis. Supplementing 1% taurine in drinking water in mice infected with T. spiralis could alleviate the burden of intestinal adult worms on days 7 and 10 postinfection (all p < 0.01) and the formation of infective muscle larvae in striated muscle during T. spiralis infection (p < 0.01). As compared with T. spiralis infection alone, taurine treatment increased the number of goblet cells on days 7, 10, and 15 (p < 0.01 and p < 0.05) and alleviated intestinal mucosal mast cell hyperplasia on days 10 and 15 (all p < 0.01). So taurine supplementation in drinking water increased infection-induced intestinal goblet cell hyperplasia and ameliorated mucosal mastocytosis. Thus, taurine can ameliorate the pathological processes of trichinellosis and may be of great value for the treatment and prevention of infection with T. spiralis and other gastrointestinal nematodes.

  8. Effect of muscle fatigue and physical activity level in motor control of the gait of young adults.

    PubMed

    Barbieri, Fabio Augusto; dos Santos, Paulo Cezar Rocha; Vitório, Rodrigo; van Dieën, Jaap H; Gobbi, Lilian Teresa Bucken

    2013-09-01

    The aim of this study was to analyze the effect of muscle fatigue in active and inactive young adults on the kinematic and kinetic parameters of normal gait and obstacle crossing. Twenty male subjects were divided into active (10) and inactive (10), based on self-reported physical activity. Participants performed three trials of two tasks (normal gait and obstacle crossing) before and after a fatigue protocol, consisting of repeated sit-to-stand transfers until the instructed pace could no longer be maintained. MANOVAs were used to compare dependent variables with the following factors: physical activity level, fatigue and task. The endurance time in the fatigue protocol was lower for the inactive group. Changes of gait parameters with fatigue, among which increased step width and increased stride speed were the most consistent, were independent of task and physical activity level. These findings indicate that the kinematic and kinetic parameters of gait are affected by muscle fatigue irrespective of the physical activity level of the subjects and type of gait. Inactive individuals used a slightly different strategy than active individuals when crossing an obstacle, independently of muscle fatigue.

  9. The Influence of Emotional State on the Masticatory Muscles Function in the Group of Young Healthy Adults

    PubMed Central

    Anna, Stocka; Joanna, Kuc; Teresa, Sierpinska; Maria, Golebiewska; Aneta, Wieczorek

    2015-01-01

    Stress may affect the function of all the components of the masticatory system and may ultimately lead to differentiated symptoms and finally to systemic and structural dysfunctions. Objective. To determine the effect of stress on the masticatory muscles function in young healthy adults. Material and Methods. A total of 201 young, Angle's first class, healthy volunteers, 103 female and 98 male, in the age between 18 and 21 years were recruited into the study. All the participants underwent clinical examination according to the Slavicek scheme, questionnaire survey according to Perceived Stress Scale, and assessment of masticatory muscles function in central occlusion. Results. Symptoms of masticatory system dysfunction were found in the group of 86 subjects (46,24%). All the muscles activity in central occlusion was comparable in female and male groups. Mean values of masseters activities in the group of low stress subjects (75,52 µV ± 15,97) were statistically different from the groups with medium (82,43 µV ± 15,04) and high (81,33 ± 12,05) perceived stress (P < 0.05). Conclusion. Chronic stress may reveal or exacerbate symptoms of masticatory dysfunction. PMID:25883942

  10. Serine-1321-independent regulation of the mu 1 adult skeletal muscle Na+ channel by protein kinase C.

    PubMed

    Bendahhou, S; Cummins, T R; Potts, J F; Tong, J; Agnew, W S

    1995-12-19

    The adult skeletal muscle Na+ channel mu1 possesses a highly conserved segment between subunit domains III and IV containing a consensus protein kinase C (PKC) phosphorylation site that, in the neuronal isoform, acts as a master control for "convergent" regulation by PKC and cAMP-dependent protein kinase. It lacks an approximately 200-aa segment between domains I and II though to modulate channel gating. We here demonstrate that mu1 is regulated by PKC (but not cAMP-dependent protein kinase) in a manner distinct from that observed for the neuronal isoforms, suggesting that under the same conditions muscle excitation could be uncoupled from motor neuron input. Maximal phosphorylation by PKC, in the presence of phosphatase inhibitors, reduced peak Na+ currents by approximately 90% by decreasing the maximal conductance, caused a -15 mV shift in the midpoint of steady-state inactivation, and caused a slight speeding of inactivation. Surprisingly, these effects were not affected by mutation of the conserved serine (serine-1321) in the interdomain III-IV loop. the pattern of current suppression and gating modification by PKC resembles the response of muscle Na+ channels to inhibitory factors present in the serum and cerebrospinal fluid of patients with Guillain-Barré syndrome, multiple sclerosis, and idiopathic demyelinating polyradiculoneuritis.

  11. Prior swimming exercise favors muscle recovery in adult female rats after joint immobilization

    PubMed Central

    Petrini, Ana Claudia; Ramos, Douglas Massoni; Gomes de Oliveira, Luana; Alberto da Silva, Carlos; Pertille, Adriana

    2016-01-01

    [Purpose] To evaluate the efficacy of pre-exercise on immobilization and subsequent recovery of white gastrocnemius (WG) and soleus (SOL) muscles of female rats. [Subjects and Methods] Thirty, 8-month-old, female Wistar rats were randomly and evenly allocated to six groups: sedentary (S); immobilized sedentary (IS); immobilized/rehabilitated sedentary (IRS); trained (T); immobilized trained (IT); and immobilized/rehabilitated trained (IRT). For four months, T, IT and IRT group animals performed swimming exercise (three sessions per week, 60 minutes per session), while S, IS and IRS groups animals remained housed in cages. After this period, the left hindlimb of the animals from the IS, IRS, IT and IRT groups was immobilized for five days, with the ankle at 90°. After removal of the orthosis, animals from the IRS and IRT groups followed a rehabilitation program based on swimming (five sessions per week, 60 minutes per session) for two weeks. [Results] Immobilization significantly reduced the cross-sectional area of the white gastrocnemius muscle; no changes were observed in the soleus muscles of the trained animals. Transforming growth factor-β1 protein levels were similar among the trained groups. [Conclusion] Prior swimming prevents hypotrophy of the soleus muscle after immobilization, and protein levels reflected the adaptive capacity of the skeletal muscle. PMID:27512267

  12. Determine the effect of neck muscle fatigue on dynamic visual acuity in healthy young adults

    PubMed Central

    Al Saif, Amer A.; Al Senany, Samira

    2015-01-01

    [Purpose] The aim of this study was to determine whether neck muscle fatigue affects dynamic visual acuity in healthy young participants. [Subjects and Methods] This study was a double-blinded, prospective, randomized, controlled trial. Thirty healthy young subjects (ages 21 to 30 years) participated in the study. Participants were randomly divided into an experimental group (n=15) and a control group (n=15). The experimental group performed an exercise designed to induce neck muscle fatigue and the control group preformed non-fatiguing sham exercises. [Results] There were significant differences in mean dynamic visual acuity between the two groups (0.26±0.11 LogMar versus 0.003±0.02 LogMar). Subjects in the experimental group showed a significant decline in their dynamic visual acuity compared with the control group. Dynamic visual acuity strongly correlated with neck muscle fatigue (r = 0.79). No significant differences in joint position error were observed between the two groups and no significant correlations between joint position error and neck muscle fatigue were observed (r = 0.23). [Conclusion] The results of this study suggest that neck muscle fatigue negatively impacts dynamic visual acuity. Although not statistically significant, cervical spine proprioception as measured by the joint position error in the experimental group was diminished after fatigue. PMID:25642087

  13. Determine the effect of neck muscle fatigue on dynamic visual acuity in healthy young adults.

    PubMed

    Al Saif, Amer A; Al Senany, Samira

    2015-01-01

    [Purpose] The aim of this study was to determine whether neck muscle fatigue affects dynamic visual acuity in healthy young participants. [Subjects and Methods] This study was a double-blinded, prospective, randomized, controlled trial. Thirty healthy young subjects (ages 21 to 30 years) participated in the study. Participants were randomly divided into an experimental group (n=15) and a control group (n=15). The experimental group performed an exercise designed to induce neck muscle fatigue and the control group preformed non-fatiguing sham exercises. [Results] There were significant differences in mean dynamic visual acuity between the two groups (0.26±0.11 LogMar versus 0.003±0.02 LogMar). Subjects in the experimental group showed a significant decline in their dynamic visual acuity compared with the control group. Dynamic visual acuity strongly correlated with neck muscle fatigue (r = 0.79). No significant differences in joint position error were observed between the two groups and no significant correlations between joint position error and neck muscle fatigue were observed (r = 0.23). [Conclusion] The results of this study suggest that neck muscle fatigue negatively impacts dynamic visual acuity. Although not statistically significant, cervical spine proprioception as measured by the joint position error in the experimental group was diminished after fatigue.

  14. Muscle tension induced after learning enhances long-term narrative and visual memory in healthy older adults.

    PubMed

    Nielson, Kristy A; Wulff, Laura L; Arentsen, Timothy J

    2014-03-01

    Arousing events are better remembered than mundane events. Indeed, manipulation of arousal, such as by muscle tension, can influence memory even when it occurs shortly after learning. Indeed, our founding study showed this approach can raise delayed memory performance in older adults to a level comparable to that of unaided young adults. Yet, systematic studies, especially those investigating different modalities or types of memory, have not been done. This study investigated the effects of a brief bout of isometric exercise via handgrip on narrative and visuospatial episodic memory in healthy elders. Forty-seven participants completed the Logical Memory subtest of the Wechsler Memory Scales III (LM) and the Benton Visual Retention Test (BVRT), followed alternately by no treatment and by moderately squeezing a sand-filled latex ball for 1-min (counterbalanced order and test forms). Isometric exercise significantly increased both positive and negative affect ratings. Retention was tested 2 weeks later. Delayed recall and recognition of LM was enhanced by arousal relative to control, as was recognition of the BVRT. The results extend past findings that muscle tension induced after learning modulates memory consolidation, extending findings in elders to suggest that a simple form of isometric exercise can have practical effects, such as aiding memory for stories and images.

  15. Heterogeneity in vascular smooth muscle cell embryonic origin in relation to adult structure, physiology, and disease

    PubMed Central

    Pfaltzgraff, Elise R.; Bader, David M.

    2015-01-01

    Regional differences in vascular physiology and disease response exist throughout the vascular tree. While these differences in physiology and disease correspond to regional vascular environmental conditions, there is also compelling evidence that the embryonic origins of the smooth muscle inherent to the vessels may play a role. Here we review what is known regarding the role of embryonic origin of vascular smooth muscle cells during vascular development. The focus of this review is to highlight the heterogeneity in the origins of vascular smooth muscle cells and the resulting regional physiologies of the vessels. Our goal is to stimulate future investigation into this area and provide a better understanding of vascular organogenesis and disease. PMID:25546231

  16. The Association between Muscle Mass Deficits Estimated from Bioelectrical Impedance Analysis and Lumbar Spine Bone Mineral Density in Korean Adults

    PubMed Central

    Jang, Hye-Yeon; Lee, Kye-Bong; Cho, Sul-Bit; Im, In Jae; Kim, Hee Jin

    2016-01-01

    Background Bone mineral density (BMD) is influenced by many factors. Despite the reported association between body components and BMD, most of these studies investigated the relationship between absolute muscle mass or fat mass and BMD in postmenopausal women or elderly subjects. The aim of this study is to investigate the association between muscle mass deficits (MMD) estimated from bioelectrical impedance analysis (BIA) and lumbar spinal BMD in Korean adults 20 to 49 years of age. Methods This cross-sectional study included 1,765 men and women who visited a health promotion center for a routine checkup. The lumbar spinal BMD was measured by dual energy X-ray absorptiometry. Body composition analysis was performed using BIA. Results The mean age of the subjects was 40.2±6.3 years. Ten thousand subjects (56.7%) were males and 126 subjects (7.1%) belonged to the low BMD (Z-score ≤-2.0). MMD had the strongest influence on BMD after adjusting for all covariates. The adjusted odds ratio of Group 3 (MDD >2.6 kg) for low BMD was 2.74 (95% CI, 1.46-5.15) after adjusting for age, gender, body mass index, height, and smoking. Conclusions MMD estimated by BIA showed a significant association with BMD and could be regarded as an independent risk factor for low BMD in adults 20 to 49 years of age. These findings support that interventions such as physical activity or lifestyle changes may simultaneously modify both muscle and bone health in this age group. PMID:27294081

  17. A continuum of myofibers in adult rabbit extraocular muscle: force, shortening velocity, and patterns of myosin heavy chain colocalization.

    PubMed

    McLoon, Linda K; Park, Han Na; Kim, Jong-Hee; Pedrosa-Domellöf, Fatima; Thompson, Ladora V

    2011-10-01

    Extraocular muscle (EOM) myofibers do not fit the traditional fiber typing classifications normally used in noncranial skeletal muscle, in part, due to the complexity of their individual myofibers. With single skinned myofibers isolated from rectus muscles of normal adult rabbits, force and shortening velocity were determined for 220 fibers. Each fiber was examined for myosin heavy chain (MyHC) isoform composition by densitometric analysis of electrophoresis gels. Rectus muscle serial sections were examined for coexpression of eight MyHC isoforms. A continuum was seen in single myofiber shortening velocities as well as force generation, both in absolute force (g) and specific tension (kN/m(2)). Shortening velocity correlated with MyHCIIB, IIA, and I content, the more abundant MyHC isoforms expressed within individual myofibers. Importantly, single fibers with similar or identical shortening velocities expressed significantly different ratios of MyHC isoforms. The vast majority of myofibers in both the orbital and global layers expressed more than one MyHC isoform, with up to six isoforms in single fiber segments. MyHC expression varied significantly and unpredictably along the length of single myofibers. Thus EOM myofibers represent a continuum in their histological and physiological characteristics. This continuum would facilitate fine motor control of eye position, speed, and direction of movement in all positions of gaze and with all types of eye movements-from slow vergence movements to fast saccades. To fully understand how the brain controls eye position and movements, it is critical that this significant EOM myofiber heterogeneity be integrated into hypotheses of oculomotor control.

  18. Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial123

    PubMed Central

    Smith, Gordon I; Atherton, Philip; Reeds, Dominic N; Mohammed, B Selma; Rankin, Debbie; Rennie, Michael J; Mittendorfer, Bettina

    2011-01-01

    Background: Loss of muscle mass with aging is a major public health concern. Omega-3 (n–3) fatty acids stimulate protein anabolism in animals and might therefore be useful for the treatment of sarcopenia. However, the effect of omega-3 fatty acids on human protein metabolism is unknown. Objective: The objective of this study was to evaluate the effect of omega-3 fatty acid supplementation on the rate of muscle protein synthesis in older adults. Design: Sixteen healthy, older adults were randomly assigned to receive either omega-3 fatty acids or corn oil for 8 wk. The rate of muscle protein synthesis and the phosphorylation of key elements of the anabolic signaling pathway were evaluated before and after supplementation during basal, postabsorptive conditions and during a hyperaminoacidemic-hyperinsulinemic clamp. Results: Corn oil supplementation had no effect on the muscle protein synthesis rate and the extent of anabolic signaling element phosphorylation in muscle. Omega-3 fatty acid supplementation had no effect on the basal rate of muscle protein synthesis (mean ± SEM: 0.051 ± 0.005%/h compared with 0.053 ± 0.008%/h before and after supplementation, respectively; P = 0.80) but augmented the hyperaminoacidemia-hyperinsulinemia–induced increase in the rate of muscle protein synthesis (from 0.009 ± 0.005%/h above basal values to 0.031 ± 0.003%/h above basal values; P < 0.01), which was accompanied by greater increases in muscle mTORSer2448 (P = 0.08) and p70s6kThr389 (P < 0.01) phosphorylation. Conclusion: Omega-3 fatty acids stimulate muscle protein synthesis in older adults and may be useful for the prevention and treatment of sarcopenia. This trial was registered at clinical trials.gov as NCT00794079. PMID:21159787

  19. Differences in histone modifications between slow- and fast-twitch muscle of adult rats and following overload, denervation, or valproic acid administration.

    PubMed

    Kawano, Fuminori; Nimura, Keisuke; Ishino, Saki; Nakai, Naoya; Nakata, Ken; Ohira, Yoshinobu

    2015-11-15

    Numerous studies have reported alterations in skeletal muscle properties and phenotypes in response to various stimuli such as exercise, unloading, and gene mutation. However, a shift in muscle fiber phenotype from fast twitch to slow twitch is not completely induced by stimuli. This limitation is hypothesized to result from the epigenetic differences between muscle types. The main purpose of the present study was to identify the differences in histone modification for the plantaris (fast) and soleus (slow) muscles of adult rats. Genome-wide analysis by chromatin immunoprecipitation followed by DNA sequencing revealed that trimethylation at lysine 4 and acetylation of histone 3, which occurs at transcriptionally active gene loci, was less prevalent in the genes specific to the slow-twitch soleus muscle. Conversely, gene loci specific to the fast-twitch plantaris muscle were associated with the aforementioned histone modifications. We also found that upregulation of slow genes in the plantaris muscle, which are related to enhanced muscular activity, is not associated with activating histone modifications. Furthermore, silencing of muscle activity by denervation caused the displacement of acetylated histone and RNA polymerase II (Pol II) in 5' ends of genes in plantaris, but minor effects were observed in soleus. Increased recruitment of Pol II induced by forced acetylation of histone was also suppressed in valproic acid-treated soleus. Our present data indicate that the slow-twitch soleus muscle has a unique set of histone modifications, which may relate to the preservation of the genetic backbone against physiological stimuli.

  20. Oogenesis-flight syndrome in crickets: age-dependent egg production, flight performance, and biochemical composition of the flight muscles in adult female Gryllus bimaculatus.

    PubMed

    Lorenz, Matthias W

    2007-08-01

    Age-dependent changes in flight performance, biochemical composition of flight muscles, and fresh mass of the flight muscles and ovaries were analysed in adult female two-spotted crickets, Gryllus bimaculatus. After the final moult the flight muscle mass increased significantly to a maximum at days 2 and 3. On day 2 the highest flight activity was also observed. Between days 2 and 3 the ovary weight started to rapidly increase due to vitellogenic egg growth, which continued at a high rate until day 10. With the onset of ovarial growth, flight performance decreased and the flight muscles started to histolyse. A high correlation between flight muscle mass and the content of protein, lipid, glycogen, and free carbohydrate in the flight muscle indicated that energy-rich substrates from the degrading flight muscles were used to fuel oogenesis, although flight muscle histolysis can provide only a small fraction of the substrates needed for egg production. In general, there was a clear trade-off between egg production and flight ability. Surprisingly, however, some females possessed well-developed ovaries but displayed no signs of flight muscle histolysis. This observation was corroborated by flight experiments which revealed that, although most flying females had small ovaries, some of them carried an appreciable amount of mature eggs, and thus, somehow managed to evade the oogenesis-flight syndrome.

  1. Impaired neural activation limits muscle power in mobility-limited older adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Declines in functional mobility are common with advancing age, though the physiological determinants underlying this problem are not fully understood. Accumulating evidence indicates that muscle power, the product of force and velocity, is an independent predictor of mobility function in older adul...

  2. Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders.

    PubMed

    Jokela, Manu; Huovinen, Sanna; Raheem, Olayinka; Lindfors, Mikaela; Palmio, Johanna; Penttilä, Sini; Udd, Bjarne

    2016-01-01

    The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary "myopathic" changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions.

  3. Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders

    PubMed Central

    Jokela, Manu; Huovinen, Sanna; Raheem, Olayinka; Lindfors, Mikaela; Palmio, Johanna; Penttilä, Sini; Udd, Bjarne

    2016-01-01

    The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary “myopathic” changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions. PMID:26999347

  4. Analytes and metabolites associated with muscle quality in young, healthy adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: Identification of mechanisms that underlie lower extremity muscle quality (leg press one repetition maximum/total lean mass; LP/Lean) may be important for individuals interested in optimizing fitness and sport performance. The purpose of the current study was to provide observational insigh...

  5. Resistance Training Enhances Skeletal Muscle Innervation Without Modifying the Number of Satellite Cells or their Myofiber Association in Obese Older Adults.

    PubMed

    Messi, María Laura; Li, Tao; Wang, Zhong-Min; Marsh, Anthony P; Nicklas, Barbara; Delbono, Osvaldo

    2016-10-01

    Studies in humans and animal models provide compelling evidence for age-related skeletal muscle denervation, which may contribute to muscle fiber atrophy and loss. Skeletal muscle denervation seems relentless; however, long-term, high-intensity physical activity appears to promote muscle reinnervation. Whether 5-month resistance training (RT) enhances skeletal muscle innervation in obese older adults is unknown. This study found that neural cell-adhesion molecule, NCAM+ muscle area decreased with RT and was inversely correlated with muscle strength. NCAM1 and RUNX1 gene transcripts significantly decreased with the intervention. Type I and type II fiber grouping in the vastus lateralis did not change significantly but increases in leg press and knee extensor strength inversely correlated with type I, but not with type II, fiber grouping. RT did not modify the total number of satellite cells, their number per area, or the number associated with specific fiber subtypes or innervated/denervated fibers. Our results suggest that RT has a beneficial impact on skeletal innervation, even when started late in life by sedentary obese older adults.

  6. Resistance Training Alters the Proportion of Skeletal Muscle Fibers but Not Brain Neurotrophic Factors in Young Adult Rats

    PubMed Central

    Antonio-Santos, José; Ferreira, Diórginis José S.; Gomes Costa, Gizelle L.; Matos, Rhowena Jane B.; Toscano, Ana E.; Manhães-de-Castro, Raul

    2016-01-01

    Abstract Antonio-Santos, J, Ferreira, DJS, Gomes Costa, GL, Matos, RJB, Toscano, AE, Manhães-de-Castro, R, and Leandro, CG. Resistance training alters the proportion of skeletal muscle fibers but not brain neurotrophic factors in young adult rats. J Strength Cond Res 30(12): 3531–3538, 2016—Resistance training (RT) is related to improved muscular strength and power output. Different programs of RT for rats have been developed, but peripheral and central response has not been evaluated directly in the same animal. To test the hypothesis that RT induces central and peripheral adaptations, this study evaluated the effects of a RT on the performance of a weekly maximum overload test, fiber-type typology, and brain neurotrophic factors in young adult rats. Thirty-one male Wistar rats (65 ± 5 days) were divided in 2 groups: nontrained (NT, n = 13) and trained (T, n = 18). Trained group was submitted to a program of RT ladder climbing, gradually added mass, 5 days per week during 8 weeks at 80% of individual maximum overload. This test was weekly performed to adjust the individual load throughout the weeks for both groups. After 48 hours from the last session of exercise, soleus and extensor digital longus (EDL) muscles were removed for myofibrillar ATPase staining analysis. Spinal cord, motor cortex, and cerebellum were removed for RT-PCR analysis of BDNF and insulin-like growth factor-1 (IGF-1) gene expression. In EDL muscle, T animals showed an increase in the proportion of type IIb fibers and a reduction of type IIa fibers. Insulin-like growth factor-1 gene expression was reduced in the cerebellum of T animals (NT: 1.025 ± 0.12; T: 0.57 ± 0.11). Our data showed that 8 weeks of RT were enough to increase maximum overload capacity and the proportion of glycolytic muscle fibers, but there were no associations with the expression of growth neurotrophic factors. PMID:27870699

  7. Adult rat motor neurons do not re-establish electrical coupling during axonal regeneration and muscle reinnervation.

    PubMed

    Favero, Morgana; Cangiano, Alberto; Busetto, Giuseppe

    2015-01-01

    Gap junctions (GJs) between neurons are present in both the newborn and the adult nervous system, and although important roles have been suggested or demonstrated in a number of instances, in many other cases a full understanding of their physiological role is still missing. GJs are expressed in the rodent lumbar cord at birth and mediate both dye and electrical coupling between motor neurons. This expression has been proposed to mediate: (i) fast synchronization of motoneuronal spike activity, in turn linked to the process of refinement of neuromuscular connections, and (ii) slow synchronization of locomotor-like oscillatory activity. Soon after birth this coupling disappears. Since in the adult rat regeneration of motor fibers after peripheral nerve injury leads to a recapitulation of synaptic refinement at the target muscles, we tested whether GJs between motor neurons are transiently re-expressed. We found that in conditions of maximal responsiveness of lumbar motor neurons (such as no depression by anesthetics, decerebrate release of activity of subsets of motor neurons, use of temporal and spatial summation by antidromic and orthodromic stimulations, testing of large ensembles of motor neurons) no firing is observed in ventral root axons in response to antidromic spike invasion of nearby counterparts. We conclude that junctional coupling between motor neurons is not required for the refinement of neuromuscular innervation in the adult.

  8. Contractile properties of skinned muscle fibres from young and adult normal and dystrophic (mdx) mice.

    PubMed Central

    Williams, D A; Head, S I; Lynch, G S; Stephenson, D G

    1993-01-01

    1. Single muscle fibres were enzymatically isolated from the soleus and extensor digitorum longus (EDL) muscles of genetically dystrophic mdx and normal (C57BL/10) mice aged 3-6 or 17-23 weeks. 2. Fibres of both muscles were chemically skinned with the non-ionic detergent Triton X-100 (2% v/v). Ca(2+)- and Sr(2+)-activated contractile responses were recorded and comparisons were made between several contractile parameters of various fibre types of normal and dystrophic mice of similar age. 3. There were no significant differences in the following contractile parameters of skinned fibres of normal and mdx mice of the same age: sensitivity to activating Ca2+ (pCa50) or Sr2+ (pSr50) and differential sensitivity to the activating ions (pCa50-pSr50). However the maximum isometric tension (Po) and the frequency of myofibrillar force oscillations in EDL fast-twitch fibres of young mdx mice were significantly lower than those of soleus fast-twitch fibres of the same animals, or fast-twitch fibres (EDL or soleus) of normal mice. 4. Age-related differences were apparent in some contractile parameters of both normal and mdx mice. In particular the steepness of force-pCa and force-pSr curves increased with age in normal mice, yet decreased with age in fibres of mdx mice. 5. A fluorescent probe, ethidium bromide, which interchelates with DNA, was used with laser-scanning confocal microscopy to determine the distribution of myonuclei in fibres. Fibres isolated from either muscle type of normal animals displayed a characteristic peripheral spiral of myonuclei. Fibres from muscles of mdx mice displayed three major patterns of nuclear distribution; the normal peripheral spiral, long central strands of nuclei, and a mixture of these two patterns. 6. The contractile characteristics of mdx fibres were not markedly influenced by the nuclear distribution pattern in that there were no discernible differences in the major contractile parameters (the Hill coefficients nCa and nSr, which

  9. Isometric strength and steadiness adaptations of the knee extensor muscles to level and downhill treadmill walking in older adults.

    PubMed

    Gault, Mandy Lucinda; Willems, Mark Elizabeth Theodorus

    2013-04-01

    An ageing related decline in muscle strength and steadiness decreases quality of life and increases the risk for falls. Downhill treadmill walking (DTW) may enhance muscle strength and steadiness in older adults. Eighteen healthy older adults (age: 67 ± 4, body mass: 75 ± 14 kg) completed 12-weeks of level treadmill walking (LTW, 0 %, n = 8) or DTW (-10 %, n = 10) (30 min, 3 days per week) at a self-selected walking speed (re-adjusted in week 4 and 8). Maximal voluntary isometric force (MVIF) and electromyography (EMG) of the m. quadriceps femoris (QF) were measured at baseline, 4, 8 and 12 weeks. Steadiness of submaximal (5, 10 and 20 % MVIF) isometric contractions (i.e. coefficient of variation of the force signal) and EMG of QF were measured at baseline and 12 weeks. Baseline MVIF of LTW (340 ± 112 N) and DTW (368 ± 128 N) increased equally by 14 ± 6 and 5 ± 6 % (p < 0.05). Steadiness at 5 %MVIF improved following 12 weeks of LTW (baseline: 0.04 ± 0.01; 12 weeks: 0.03 ± 0.01) and DTW (baseline: 0.04 ± 0.02; 12 weeks: 0.03 ± 0.01 (p < 0.05). EMG root mean square of m. vastus lateralis during MVIF increased by 38 % following 12 weeks of LTW only (p < 0.05). The potential implications for an exercise modality, such as DTW, with a lower oxygen demand, to improve muscle strength could serve as a rehabilitative countermeasure for older adults.

  10. A pilot study examining the impact of exercise training on skeletal muscle genes related to the TLR signaling pathway in older adults following hip fracture recovery.

    PubMed

    McKenzie, Alec I; Briggs, Robert A; Barrows, Katherine M; Nelson, Daniel S; Kwon, Oh Sung; Hopkins, Paul N; Higgins, Thomas F; Marcus, Robin L; Drummond, Micah J

    2017-01-01

    Older adults after hip fracture surgery experience progressive muscle atrophy and weakness, limiting full recovery. Further understanding of the molecular mechanisms in muscle with adaptation to exercise training in this vulnerable population is necessary. Therefore, we conducted a pilot study to investigate the skeletal muscle inflammatory and ceramide biosynthesis gene expression levels associated with the toll-like receptor (TLR) pathway before (Pre) and following a 3-mo multicomponent exercise training program in older adults (3M, 4F; 78.4 ± 13.3 yr; 25.5 ± 2.3 kg/m(2)) ~4 mo after repair from hip fracture (HipFx). Vastus lateralis biopsies from the surgical limb were obtained before (Pre) and after training. Molecular end points and muscle function data were also compared with matched nonexercise healthy controls (CON). As a follow-up analysis, we evaluated specific sphingolipid pools in HipFx and CON muscle. Following training, quadriceps cross-sectional area, strength, and 6-min walk (6MW) increased in the surgical limb (P < 0.05). Additionally, MYD88, TAK1, NFKB1, IL6, SPT2, and CERS1 gene expression decreased after training (P ≤ 0.05), but some remained elevated above CON levels. Interestingly, MYD88 mRNA was inversely correlated to quadriceps CSA, strength, and 6MW. Finally, muscle dihydroceramides and phosphoceramides in HipFx were lower than CON at Pre (P ≤ 0.05), but after training differences from CON were removed. Together, our pilot data support that exercise training alters skeletal muscle inflammation and ceramide metabolism associated with TLR signaling in older adults recovering from hip fracture surgery and may be related to improvements in muscle function recovery.

  11. [An Adult Case of Transperineal Repair of Congenital Rectourethral Fistula Using Gracilis Muscle Flap Interposition].

    PubMed

    Yo, Toeki; Kanematsu, Akihiro; Hanasaki, Takeshi; Nakanishi, Yukako; Togo, Yoshikazu; Suzuki, Toru; Higuchi, Yoshihide; Nojima, Michio; Yamamoto, Shingo; Okuyama, Hiroomi

    2015-07-01

    A man in his 50s was referred to our hospital after recurrent severe urinary tract infection. He had undergone anoplasty for anorectal malformation during early infancy. He noticed urinary leakage from the anus for a long time. Under diagnosis of congenital rectourethral fistula, we performed fistula closure. The fistula was transsected via transperineal incision and each stump was closed. A gracilis muscle flap approximately 30 cm long was harvested from the left thigh, brought into the deepest part between the separated rectum and urethra through a subcutaneous tunnel and fixed there. The urinary leakage from the anus disappeared, and the infection resolved. Application of gracilis muscle flap for congenital diseases is rare, but was useful in the present case.

  12. Feasibility of resistance training in adult McArdle patients: clinical outcomes and muscle strength and mass benefits.

    PubMed

    Santalla, Alfredo; Munguía-Izquierdo, Diego; Brea-Alejo, Lidia; Pagola-Aldazábal, Itziar; Díez-Bermejo, Jorge; Fleck, Steven J; Ara, Ignacio; Lucia, Alejandro

    2014-01-01

    We analyzed the effects of a 4-month resistance (weight lifting) training program followed by a 2-month detraining period in 7 adult McArdle patients (5 female) on: muscle mass (assessed by DXA), strength, serum creatine kinase (CK) activity and clinical severity. Adherence to training was ≥84% in all patients and no major contraindication or side effect was noted during the training or strength assessment sessions. The training program had a significant impact on total and lower extremities' lean mass (P < 0.05 for the time effect), with mean values increasing with training by +855 g (95% confidence interval (CI): 30, 1679) and +547 g (95%CI: 116, 978), respectively, and significantly decreasing with detraining. Body fat showed no significant changes over the study period. Bench press and half-squat performance, expressed as the highest value of average muscle power (W) or force (N) in the concentric-repetition phase of both tests showed a consistent increase over the 4-month training period, and decreased with detraining. Yet muscle strength and power detraining values were significantly higher than pre-training values, indicating that a training effect was still present after detraining. Importantly, all the participants, with no exception, showed a clear gain in muscle strength after the 4-month training period, e.g., bench press: +52 W (95% CI: 13, 91); half-squat: +173 W (95% CI: 96, 251). No significant time effect (P > 0.05) was noted for baseline or post strength assessment values of serum CK activity, which remained essentially within the range reported in our laboratory for McArdle patients. All the patients changed to a lower severity class with training, such that none of them were in the highest disease severity class (3) after the intervention and, as such, they did not have fixed muscle weakness after training. Clinical improvements were retained, in all but one patient, after detraining, such that after detraining all patients were classed as

  13. Adipogenic healing in adult mice by implantation of hollow devices in muscle.

    PubMed

    Xaymardan, Munira; Gibbins, John R; Zoellner, Hans

    2002-05-01

    In mammals, wound healing is thought to result in the formation of scar tissue, with the exception of bony healing after fractures. Here we describe a previously unknown pattern of wound healing in which adipose rather than scar tissue is formed. Adipogenesis is normally confined to the embryo, although there are several experimental models for adipogenesis with highly specific dietary, cytokine, matrix, sex, or age requirements. The adipogenic healing described in this work provides a simple and reproducible experimental mouse model for adipogenesis without these limitations. Mice received intramuscular implants of nylon mesh material. Fibrinous material impregnated implants and within 4 weeks was replaced with highly vascular granulation tissue, typical of wound healing. Also consistent with wound healing was a reduction in vascularity of the newly formed tissue over time (P < 0.05). Lipoblasts were prevalent in granulation tissue, reaching a maximum in week 2 (P < 0.001) but falling to very low levels by week 9. These cells matured to adipocytes, with intermediate forms being seen. The identity of lipoblasts and adipocytes was confirmed by Oil Red O staining and electron microscopy. Control experiments confirmed that adipogenesis was independent of the materials used as well as of the sex and age of the animals. Rather, adipogenesis appeared to be due to replacement of fibrinous material in a space created within muscle. It is possible that adipogenic healing represents an adaptation for limiting the formation of restrictive scar tissues within muscle, and that this is the basis for the formation of traumatic lipomas in humans. Also, muscle tissue is replaced by adipose cells, seemingly derived from pluripotential satellite cells, in several degenerative muscle conditions, suggesting a role for adipogenic healing in these conditions.

  14. Comparison of the tension responses to ramp shortening and lengthening in intact mammalian muscle fibres: crossbridge and non-crossbridge contributions.

    PubMed

    Roots, H; Offer, G W; Ranatunga, K W

    2007-01-01

    We examined the tension responses to ramp shortening and lengthening over a range of velocities (0.1-5 L(0)/s) and at 20 degrees C and 30 degrees C in tetanized intact fibre bundles from a rat fast (flexor hallucis brevis) muscle; fibre length (L(0)) was 2.2 mm and sarcomere length approximately 2.5 microm. The tension change during ramp releases as well as ramp stretches showed an early transition (often appearing as an inflection) at 1-4 ms; the tension change at this transition and the length change at which it occurred increased with velocity. A second transition, indicated by a more gradual reduction in slope, occurred when the length had changed by 14-28 nm per half-sarcomere; the tension at this transition increased with lengthening velocity towards a plateau and it decreased with shortening velocity towards zero tension. The velocity dependence of the time to the transitions and the length change at the transitions showed some asymmetries between shortening and lengthening. Based on analyses of the velocity dependence of the tension and modelling, we propose that the first transition reflects the tension change associated with the crossbridge power stroke in shortening, or with the reversal of the power stroke in lengthening. Modelling shows that the reduction in slope at the second transition occurs when most of the crossbridges (myosin heads) that were attached at the start of the ramp become detached. After the second transition, the tension reaches a steady level in the model whereas the tension continues to increase during lengthening and continues to decrease during shortening in the experiments; this continuous tension change is seen at a wide range of initial sarcomere lengths and when active force is reduced by the myosin inhibitor, BTS. The continuous tension decline during shortening is not abolished by caffeine, but the rate of decline is reduced when the active force is depressed by BTS. We propose that stiffening of non-crossbridge visco

  15. Transcriptional profiling and miRNA-dependent regulatory network analysis of longissimus dorsi muscle during prenatal and adult stages in two distinct pig breeds.

    PubMed

    Siengdee, P; Trakooljul, N; Murani, E; Schwerin, M; Wimmers, K; Ponsuksili, S

    2013-08-01

    MicroRNAs (miRNAs) and mRNAs establish a complex regulatory network influencing diverse biological pathways including muscle development and growth. Elucidating miRNA-dependent regulatory networks involved in muscle development could provide additional insights into muscle traits largely predefined during prenatal development. The present study aimed to determine differentially expressed transcripts and functional miRNA-mRNA relationships associated with different stages of skeletal muscle development in two pig breeds, German Landrace and Pietrain, distinct in muscle characteristics. A comparative transcriptional profiling of longissimus dorsi muscle tissues from fetuses at 35, 63 and 91 days post-conception as well as adult pigs (180 days postnatum) was performed using the Affymetrix GeneChip porcine genome microarray. Differential expression patterns were identified to be associated with muscularly developmental stages and breed types. The integration of miRNA expression data and ingenuity pathways analysis (ipa) pathway analysis revealed several miRNA-dependent regulatory networks related to muscle growth and development. The present results provide insights into muscle biology for further improvement of porcine meat quality.

  16. Long-term delivery of FGF-6 changes the fiber type and fatigability of muscle reinnervated from embryonic neurons transplanted into adult rat peripheral nerve.

    PubMed

    Grumbles, Robert M; Casella, Gizelda T B; Rudinsky, Michelle J; Wood, Patrick M; Sesodia, Sanjay; Bent, Melissa; Thomas, Christine K

    2007-07-01

    Motoneuron death leads to muscle denervation and atrophy. Transplantation of embryonic neurons into peripheral nerves results in reinnervation and provides a strategy to rescue muscles from atrophy independent of neuron replacement in a damaged or diseased spinal cord. But the count of regenerating axons always exceeds the number of motor units in this model, so target-derived trophic factor levels may limit reinnervation. Our aim was to examine whether long-term infusion of fibroblast growth factor-6 (FGF-6) into denervated medial gastrocnemius muscles improved the function of muscles reinnervated from neurons transplanted into nerve of adult Fischer rats. Factor delivery (10 microg, 4 weeks) began after sciatic nerve transection. After a week of nerve degeneration, 1 million embryonic day 14-15 ventral spinal cord cells were transplanted into the distal tibial stump as a neuron source. Ten weeks later, neurons that expressed motoneuron markers survived in the nerves. More myelinated axons were in nerves to saline-treated muscles than in FGF-6-treated muscles. However, each group showed comparable reductions in muscle fiber atrophy because of reinnervation. Mean reinnervated fiber area was 43%-51% of non-denervated fibers. Denervated fiber area averaged 11%. FGF-6-treated muscles were more fatigable than other reinnervated muscles but had stronger motor units and fewer type I fibers than did saline-treated muscles. FGF-6 thus influenced function by changing the type of fiber reinnervated by transplanted neurons. Deficits in FGF-6 may also contribute to the increase in type I fibers in muscles reinnervated from peripheral axons, suggesting that the effects of FGF-6 on fiber type are independent of the neuron source used for reinnervation.

  17. DNA binding and transcriptional regulatory activity of mammalian achaete-scute homologous (MASH) proteins revealed by interaction with a muscle-specific enhancer.

    PubMed

    Johnson, J E; Birren, S J; Saito, T; Anderson, D J

    1992-04-15

    The MASH genes are vertebrate homologues of achaete-scute, genes required for neuronal determination in Drosophila. The sequence of MASH1 and MASH2 contains a basic helix-loop-helix (bHLH) motif that is present in other transcriptional regulators such as MyoD and E12. In the absence of an authentic target for the MASH proteins, we examined their DNA binding and transcriptional regulatory activity by using a binding site (the E box) from the muscle creatine kinase (MCK) gene, a target of MyoD. Like myogenic bHLH proteins, the MASH proteins form heterooligomers with E12 that bind the MCK E box with high affinity in vitro. Unexpectedly, however, MASH1 and MASH2 also activate transcription of both exogenous and endogenous MCK in transfected C3H/10T1/2 fibroblasts. However, they do not induce myogenesis. Myogenic activity is not exclusively a property of the MyoD basic region, as substitution of this domain fails to confer myogenic activity on MASH1. These data suggest that different bHLH proteins may activate overlapping but distinct sets of target genes in the same cell type.

  18. Sodium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium. Evidence from aequorin-loaded ferret ventricular muscles.

    PubMed Central

    Kihara, Y; Sasayama, S; Inoko, M; Morgan, J P

    1994-01-01

    We tested the hypothesis that the intracellular Ca2+ overload of ventricular myocardium during the period of posthypoxic reoxygenation is mediated by transsarcolemmal Ca2+ influx via Na+/Ca2+ exchange. In aequorin-loaded, ferret right ventricular papillary muscles, blockers of the sarcolemmal and the sarcoplasmic reticulum Ca2+ channels, slowed the Cai2+ transient, producing a convex ascent during membrane depolarization, followed by a concave descent during repolarization. The magnitude of the Cai2+ transient was affected by changes in the membrane potential, Nai+, Nao+, and Cao2+, and was blocked by Ni2+, or dichlorbenzamil. The calculated Na+/Ca2+ exchange current was in the reverse mode (Ca2+ influx) during the ascending phase of the Cai2+ transient, and was abruptly switched to the forward mode (Ca2+ efflux) at repolarization, matching the time course of the Cai2+ transient. During hypoxic superfusion, the Cai2+ transient was abbreviated, which was associated with a shorter action potential duration. In contrast, immediately after reoxygenation, the Cai2+ transient increased to a level greater than that of the control, even though the action potential remained abbreviated. This is the first demonstration on a beat-to-beat basis that, during reoxygenation, Ca2+ influx via Na+/Ca2+ exchange is augmented and transports a significant amount of Ca2+ into the ventricular myocardial cell. The activation of the exchanger at the time of reoxygenation appears to be mediated by Nai+ accumulation, which occurs during hypoxia. PMID:8132766

  19. The Effects of Proprioceptive Neuromuscular Facilitation Stretching on Post-Exercise Delayed Onset Muscle Soreness in Young Adults.

    PubMed

    McGRATH, Ryan P; Whitehead, James R; Caine, Dennis J

    Until recently, the scientific community believed that post-exercise stretching could reduce delayed onset muscle soreness (DOMS), but recent reviews of studies on the topic have concluded that pre- or post-exercise static stretching has no effect on mitigating DOMS. However, the effect of proprioceptive neuromuscular facilitation (PNF) post-exercise stretching on preventing DOMS has not been adequately studied. The purpose of this study was to determine the effect of post-exercise PNF stretching on DOMS. Young adult participants (N=57) were randomly assigned to a PNF stretching group (n=19), a static stretching group (n=20), and to a no-stretching control group (n=18). All participants completed exercise designed to induce DOMS prior to post-exercise experimental stretching protocols. Participants rated their soreness level on a pain scale 24 and 48 hours post-exercise. A 3 × 2 mixed ANOVA showed there was an effect for time (p<.01). Post hoc testing revealed that DOMS pain significantly decreased (p<.05) from 24 to 48 hours post-exercise for the PNF and control groups, but not for the static stretching group. Other analyses revealed a significant correlation (r=.61, p<.01) between the pre- and post-exercise stretch scores and the 48 hour post-exercise pain score for the PNF group. Consistent with the results of previous research on post-exercise static stretching, these results indicate that post-exercise PNF stretching also does not prevent DOMS. However, the correlation analysis suggests it is possible the pre-stretch muscle contractions of the post-exercise PNF protocol may have placed a load on an already damaged muscle causing more DOMS for some participants.

  20. The Effects of Proprioceptive Neuromuscular Facilitation Stretching on Post-Exercise Delayed Onset Muscle Soreness in Young Adults

    PubMed Central

    McGRATH, RYAN P.; WHITEHEAD, JAMES R.; CAINE, DENNIS J.

    2014-01-01

    Until recently, the scientific community believed that post-exercise stretching could reduce delayed onset muscle soreness (DOMS), but recent reviews of studies on the topic have concluded that pre- or post-exercise static stretching has no effect on mitigating DOMS. However, the effect of proprioceptive neuromuscular facilitation (PNF) post-exercise stretching on preventing DOMS has not been adequately studied. The purpose of this study was to determine the effect of post-exercise PNF stretching on DOMS. Young adult participants (N=57) were randomly assigned to a PNF stretching group (n=19), a static stretching group (n=20), and to a no-stretching control group (n=18). All participants completed exercise designed to induce DOMS prior to post-exercise experimental stretching protocols. Participants rated their soreness level on a pain scale 24 and 48 hours post-exercise. A 3 × 2 mixed ANOVA showed there was an effect for time (p<.01). Post hoc testing revealed that DOMS pain significantly decreased (p<.05) from 24 to 48 hours post-exercise for the PNF and control groups, but not for the static stretching group. Other analyses revealed a significant correlation (r=.61, p<.01) between the pre- and post-exercise stretch scores and the 48 hour post-exercise pain score for the PNF group. Consistent with the results of previous research on post-exercise static stretching, these results indicate that post-exercise PNF stretching also does not prevent DOMS. However, the correlation analysis suggests it is possible the pre-stretch muscle contractions of the post-exercise PNF protocol may have placed a load on an already damaged muscle causing more DOMS for some participants. PMID:27182398

  1. Short-Term Regulation of Excitation-Contraction Coupling by the β1a Subunit in Adult Mouse Skeletal Muscle

    PubMed Central

    García, María C.; Carrillo, Elba; Galindo, José M.; Hernández, Ascensión; Copello, Julio A.; Fill, Michael; Sánchez, Jorge A.

    2005-01-01

    The β1a subunit of the skeletal muscle voltage-gated Ca2+ channel plays a fundamental role in the targeting of the channel to the tubular system as well as in channel function. To determine whether this cytosolic auxiliary subunit is also a regulatory protein of Ca2+ release from the sarcoplasmic reticulum in vivo, we pressure-injected the β1a subunit into intact adult mouse muscle fibers and recorded, with Fluo-3 AM, the intracellular Ca2+ signal induced by the action potential. We found that the β1a subunit significantly increased, within minutes, the amplitude of Ca2+ release without major changes in its time course. β1a subunits with the carboxy-terminus region deleted did not show an effect on Ca2+ release. The possibility that potentiation of Ca2+ release is due to a direct interaction between the β1a subunit and the ryanodine receptor was ruled out by bilayer experiments of RyR1 single-channel currents and also by Ca2+ flux experiments. Our data suggest that the β1a subunit is capable of regulating E-C coupling in the short term and that the integrity of the carboxy-terminus region is essential for its modulatory effect. PMID:16183888

  2. Cytoplasm-to-myonucleus ratios and succinate dehydrogenase activities in adult rat slow and fast muscle fibers

    NASA Technical Reports Server (NTRS)

    Tseng, B. S.; Kasper, C. E.; Edgerton, V. R.

    1994-01-01

    The relationship between myonuclear number, cellular size, succinate dehydrogenase activity, and myosin type was examined in single fiber segments (n = 54; 9 +/- 3 mm long) mechanically dissected from soleus and plantaris muscles of adult rats. One end of each fiber segment was stained for DNA before quantitative photometric analysis of succinate dehydrogenase activity; the other end was double immunolabeled with fast and slow myosin heavy chain monoclonal antibodies. Mean +/- S.D. cytoplasmic volume/myonucleus ratio was higher in fast and slow plantaris fibers (112 +/- 69 vs. 34 +/- 21 x 10(3) microns3) than fast and slow soleus fibers (40 +/- 20 vs. 30 +/- 14 x 10(3) microns3), respectively. Slow fibers always had small volumes/myonucleus, regardless of fiber diameter, succinate dehydrogenase activity, or muscle of origin. In contrast, smaller diameter (< 70 microns) fast soleus and plantaris fibers with high succinate dehydrogenase activity appeared to have low volumes/myonucleus while larger diameter (> 70 microns) fast fibers with low succinate dehydrogenase activity always had large volume/myonucleus. Slow soleus fibers had significantly greater numbers of myonuclei/mm than did either fast soleus or fast plantaris fibers (116 +/- 51 vs. 55 +/- 22 and 44 +/- 23), respectively. These data suggest that the myonuclear domain is more limited in slow than fast fibers and in the fibers with a high, compared to a low, oxidative metabolic capability.

  3. Embryonic even skipped-Dependent Muscle and Heart Cell Fates Are Required for Normal Adult Activity, Heart Function, and Lifespan

    PubMed Central

    Fujioka, Miki; Wessells, Robert J.; Han, Zhe; Liu, Jiandong; Fitzgerald, Kerry; Yusibova, Galina L.; Zamora, Monica; Ruiz-Lozano, Pilar; Bodmer, Rolf; Jaynes, James B.

    2009-01-01

    The Drosophila pair-rule gene even skipped (eve) is required for embryonic segmentation and later in specific cell lineages in both the nervous system and the mesoderm. We previously generated eve mesoderm-specific mutants by combining an eve null mutant with a rescuing transgene that includes the entire locus, but with the mesodermal enhancer removed. This allowed us to analyze in detail the defects that result from a precisely targeted elimination of mesodermal eve expression in the context of an otherwise normal embryo. Absence of mesodermal eve causes a highly selective loss of the entire eve-expressing lineage in this germ layer, including those progeny that do not continue to express eve, suggesting that mesodermal eve precursor specification is not implemented. Despite the resulting absence of a subset of muscles and pericardial cells, mesoderm-specific eve mutants survive to fertile adulthood, providing an opportunity to examine the effects of these developmental abnormalities on adult fitness and heart function. We find that in these mutants, flying ability, myocardial performance under normal and stressed conditions, and lifespan are severely reduced. These data imply a nonautonomous role of the affected pericardial cells and body wall muscles in developing and/or maintaining cardiac performance and possibly other functions contributing to normal lifespan. Given the similarities of molecular-genetic control between Drosophila and vertebrates, these findings suggest that peri/epicardial influences may well be important for proper myocardial function. PMID:16239588

  4. HL-1 cells: a cardiac muscle cell line that contracts and retains phenotypic characteristics of the adult cardiomyocyte.

    PubMed

    Claycomb, W C; Lanson, N A; Stallworth, B S; Egeland, D B; Delcarpio, J B; Bahinski, A; Izzo, N J

    1998-03-17

    We have derived a cardiac muscle cell line, designated HL-1, from the AT-1 mouse atrial cardiomyocyte tumor lineage. HL-1 cells can be serially passaged, yet they maintain the ability to contract and retain differentiated cardiac morphological, biochemical, and electrophysiological properties. Ultrastructural characteristics typical of embryonic atrial cardiac muscle cells were found consistently in the cultured HL-1 cells. Reverse transcriptase-PCR-based analyses confirmed a pattern of gene expression similar to that of adult atrial myocytes, including expression of alpha-cardiac myosin heavy chain, alpha-cardiac actin, and connexin43. They also express the gene for atrial natriuretic factor. Immunohistochemical staining of the HL-1 cells indicated that the distribution of the cardiac-specific markers desmin, sarcomeric myosin, and atrial natriuretic factor was similar to that of cultured atrial cardiomyocytes. A delayed rectifier potassium current (IKr) was the most prominent outward current in HL-1 cells. The activating currents displayed inward rectification and deactivating current tails were voltage-dependent, saturated at >+20 mV, and were highly sensitive to dofetilide (IC50 of 46.9 nM). Specific binding of [3H]dofetilide was saturable and fit a one-site binding isotherm with a Kd of 140 +/- 60 nM and a Bmax of 118 fmol per 10(5) cells. HL-1 cells represent a cardiac myocyte cell line that can be repeatedly passaged and yet maintain a cardiac-specific phenotype.

  5. Dose-dependent effect of Bisphenol-A on insulin signaling molecules in cardiac muscle of adult male rat.

    PubMed

    Sivashanmugam, Preethi; Mullainadhan, Vigneswari; Karundevi, Balasubramanian

    2017-03-25

    Environmental contaminant, Bisphenol-A (BPA) is a xenoestrogen, an essential component used for the production of two classes of polymers such as polycarbonate and epoxy resin which disrupts the normal endocrine function. BPA has intense effects on mice endocrine pancreas, an essential tissue involved in glucose metabolism. It disrupts pancreatic β-cell insulin content, induces hyperinsulinemia and insulin resistance in male rats. Cardiac muscle is an insulin responsive organ and insulin has direct effects on glucose transport. The present study was designed to assess the effect of BPA on insulin signaling molecules in the cardiac muscle of adult male Wistar rat. Adult male Wistar rats (200-250 g) were selected and divided into following groups: Group 1: Control (vehicle treated), Group 2: Rats treated with 10 mg BPA/kg b.wt./day for 30 days orally, Group 3: Rats treated with 100 mg BPA/kg b.wt./day for 30 days orally, Group 4: Rats treated with 400 mg BPA/kg b.wt./day for 30 days orally. IR (insulin receptor) and pIR(Tyr1162) proteins were significantly decreased in the high dose group (400 mg). There was no change in IRS1 (insulin receptor substrate-1) and Akt proteins. Whereas, a decrease in pIRS1(Tyr632) (100 mg and 400 mg), pAkt (Ser473) (400 mg) and GLUT4 (glucose transporter 4) (cytosolic and plasma membrane) proteins was observed which may affect the cardiovascular function. It is concluded that BPA exposure has adverse effect on cardiac insulin signal transduction which may affect its function.

  6. Eccentric contraction-induced injury to type I, IIa, and IIa/IIx muscle fibers of elderly adults.

    PubMed

    Choi, Seung Jun; Lim, Jae-Young; Nibaldi, Eva G; Phillips, Edward M; Frontera, Walter R; Fielding, Roger A; Widrick, Jeffrey J

    2012-02-01

    Muscles of old laboratory rodents experience exaggerated force losses after eccentric contractile activity. We extended this line of inquiry to humans and investigated the influence of fiber myosin heavy chain (MHC) isoform content on the injury process. Skinned muscle fiber segments, prepared from vastus lateralis biopsies of elderly men and women (78 ± 2 years, N = 8), were subjected to a standardized eccentric contraction (strain, 0.25 fiber length; velocity, 0.50 unloaded shortening velocity). Injury was assessed by evaluating pre- and post-eccentric peak Ca(2+)-activated force per fiber cross-sectional area (F (max)). Over 90% of the variability in post-eccentric F (max) could be explained by a multiple linear regression model consisting of an MHC-independent slope, where injury was directly related to pre-eccentric F (max), and MHC-dependent y-intercepts, where the susceptibility to injury could be described as type IIa/IIx fibers > type IIa fibers > type I fibers. We previously reported that fiber type susceptibility to the same standardized eccentric protocol was type IIa/IIx > type IIa = type I for vastus lateralis fibers of 25-year-old adults (Choi and Widrick, Am J Physiol Cell Physiol 299:C1409-C1417, 2010). Modeling combined data sets revealed significant age by fiber type interactions, with post-eccentric F (max) deficits greater for type IIa and type IIa/IIx fibers from elderly vs. young subjects at constant pre-eccentric F (max). We conclude that the resistance of the myofilament lattice to mechanical strain has deteriorated for type IIa and type IIa/IIx, but not for type I, vastus lateralis fibers of elderly adults.

  7. Experimental selection for body size at age modifies early life-history traits and muscle gene expression in adult zebrafish.

    PubMed

    Amaral, Ian P G; Johnston, Ian A

    2012-11-15

    The short generation time of the zebrafish (Danio rerio) was exploited to investigate the effects of selection for body size at age on early life-history traits and on the transcriptional response to a growth stimulus in skeletal muscle of adult fish. Replicate populations were either unselected (U-lineage) or subjected to four generations of experimental selection for small (S-lineage) or large (L-lineage) body size at 90 days post-fertilization. Body mass was on average 16.3% and 41.0% higher in the L- than in the U- and S-lineages, respectively. Egg diameter was 6.4% lower with 13% less yolk in the S-lineage compared with the other lineages. Maternal transcripts for igf2r, bmpr1aa, igf1ar, igf2a, igfbp5a, ghra and igfbp3 in 2-4 cell stage embryos were higher in the L- than in the S-lineage. Larvae from the L-lineage were significantly larger, but survivorship at the end of the first month was similar between lineages. Gene expression was measured in the fast muscle of adult fish fasted for 7 days and then re-fed to satiation for 48 h. The expression of 11 insulin-like growth factor pathway genes and 12 other nutritionally responsive genes was similar for the S- and L-lineages as was gut fullness with feeding. Transcript abundance for four genes (igf1a, igf2r, igfbp1a and igfbp1b) showed either regulated or constitutive differences between the S- and L-lineages. For example, igf2 receptor transcript abundance was higher and igbp1a/b transcript abundance was lower in the L- than in the S-lineage, consistent with an effect of selection on insulin-like growth factor signalling.

  8. Efficacy of whey protein supplementation on resistance exercise-induced changes in muscle strength, lean mass, and function in mobility-limited older adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Whey protein supplementation may augment resistance exercise-induced increases in muscle strength and mass. Further studies are required to determine whether this effect extends to functionally compromised older adults. The objectives of the study were to compare the effects of whey protein concent...

  9. The relationship between vitamin D status and muscle strength in young healthy adults from sunny climate countries currently living in the northeast of Scotland.

    PubMed

    Jamil, N A; Gray, S R; Fraser, W D; Fielding, S; Macdonald, H M

    2017-04-01

    The current study examined the relationship between vitamin D status and muscle strength in young healthy adults: residents (>6 months) and newcomers (0-3 months), originally from sunny climate countries but currently living in the northeast of Scotland. Our longitudinal data found a positive, albeit small, relationship between vitamin D status and knee extensor isometric strength.

  10. Botulinum toxin in masticatory muscles of the adult rat induces bone loss at the condyle and alveolar regions of the mandible associated with a bone proliferation at a muscle enthesis.

    PubMed

    Kün-Darbois, Jean-Daniel; Libouban, Hélène; Chappard, Daniel

    2015-08-01

    In man, botulinum toxin type A (BTX) is injected in masticatory muscles for several indications such as trismus, bruxism, or masseter hypertrophy. Bone changes in the mandible following BTX injections in adult animal have therefore became a subject of interest. The aim of this study was to analyze condylar and alveolar bone changes following BTX unilateral injections in masseter and temporal muscles in adult rats. Mature male rats (n = 15) were randomized into 2 groups: control (CTRL; n = 6) and BTX group (n= 9). Rats of the BTX group received a single injection of BTX into right masseter and temporal muscles. Rats of the CTRL group were similarly injected with saline solution. Rats were sacrificed 4 weeks after injections. Masticatory muscles examination and microcomputed tomography (microCT) were performed. A significant difference of weight was found between the 2 groups at weeks 2, 3 and 4 (p < 0.05). Atrophy of the right masseter and temporal muscles was observed in all BTX rats. MicroCT analysis showed significant bone loss in the right alveolar and condylar areas in BTX rats. Decrease in bone volume reached -20% for right alveolar bone and -35% for right condylar bone. A hypertrophic bone metaplasia at the digastric muscle enthesis was found on every right hemimandible in the BTX group and none in the CTRL group. BTX injection in masticatory muscles leads to a significant and major mandible bone loss. These alterations can represent a risk factor for fractures in human. The occurrence of a hypertrophic bone metaplasia at the Mus Digastricus enthesis may constitute an etiological factor for tori.

  11. Higher Protein Intake Is Associated with Higher Lean Mass and Quadriceps Muscle Strength in Adult Men and Women12

    PubMed Central

    Sahni, Shivani; Mangano, Kelsey M; Hannan, Marian T; Kiel, Douglas P; McLean, Robert R

    2015-01-01

    Background: The impact of dietary protein intake on lower extremity lean mass and strength in community-dwelling adult Americans is not fully understood. Objectives: The objective was to determine the associations between total protein (TP), animal protein (AP), and plant protein (PP) intakes and lean mass of the legs and quadriceps muscle strength. We further examined whether the associations with quadriceps strength may be explained by lean mass of the legs. Methods: This cross-sectional study included men (n = 1166) and women (n = 1509) from the Framingham Offspring Cohort in Massachusetts. Protein intake in grams per day was measured in either 1995–1998 or 1998–2001. Leg lean mass and isometric quadriceps strength, both in kilograms, were measured in 1996–2001. Multilinear regression models estimated adjusted least squares means of each of the muscle measures by quartile categories of protein intake, adjusting for relevant confounders and covariates. Results: Mean age was 59 ± 9 y (range: 29–86 y) and TP intake was 80 ± 27 g/d in men and 76 ± 26 g/d in women. In men and women, leg lean mass was higher in participants in the highest quartiles of TP and AP intake compared with those in the lowest quartiles of intake [least squares means (kg): TP—17.6 vs. 17.1 in men, P-trend: 0.005, and 11.7 vs. 11.4 in women, P-trend: 0.006; AP—17.6 vs. 17.1 in men, P-trend: 0.002, and 11.7 vs. 11.4 in women, P-trend: 0.003]. PP intake was not associated with lean mass in either sex. In men and women, quadriceps strength was higher in participants in the highest quartile of PP intake compared with those in the lowest quartile [least squares means (kg): 22.9 vs. 21.7 in men, P-trend: 0.01, and 19.0 vs. 18.2 in women, P-trend: 0.01]; this association was no longer significant after adjustment for fruit and vegetable intake (P-trend: 0.06 in men and 0.10 in women). Although no significant association was observed for AP intake in either sex, nonsignificant protective

  12. Protecting Skeletal Muscle with Protein and Amino Acid during Periods of Disuse

    PubMed Central

    Galvan, Elfego; Arentson-Lantz, Emily; Lamon, Séverine; Paddon-Jones, Douglas

    2016-01-01

    Habitual sedentary behavior increases risk of chronic disease, hospitalization and poor quality of life. Short-term bed rest or disuse accelerates the loss of muscle mass, function, and glucose tolerance. Optimizing nutritional practices and protein intake may reduce the consequences of disuse by preserving metabolic homeostasis and muscle mass and function. Most modes of physical inactivity have the potential to negatively impact the health of older adults more than their younger counterparts. Mechanistically, mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis are negatively affected by disuse. This contributes to reduced muscle quality and is accompanied by impaired glucose regulation. Simply encouraging increased protein and/or energy consumption is a well-intentioned, but often impractical strategy to protect muscle health. Emerging evidence suggests that leucine supplemented meals may partially and temporarily protect skeletal muscle during disuse by preserving anabolism and mitigating reductions in mass, function and metabolic homeostasis. PMID:27376322

  13. Regulation of the nuclear export of the transcription factor NFATc1 by protein kinases after slow fibre type electrical stimulation of adult mouse skeletal muscle fibres.

    PubMed

    Shen, Tiansheng; Cseresnyés, Zoltán; Liu, Yewei; Randall, William R; Schneider, Martin F

    2007-03-01

    The transcription factor nuclear factor of activated T cells (NFAT)c1 has been shown to be involved in turning on slow skeletal muscle fibre gene expression. Previous studies from our laboratory have characterized the stimulation pattern-dependent nuclear import and resting shuttling of NFATc1-green fluorescent protein (GFP) in flexor digitorum brevis (FDB) muscle fibres from adult mouse. In this study, we use viral expression of the transcription factor NFATc1-GFP fusion protein to investigate the mechanisms underlying the nuclear export of the NFATc1-GFP that accumulated in the nuclei of cultured dissociated adult mouse FDB muscle fibres during slow-twitch fibre type electrical stimulation. In these studies, we found that inhibition of either glycogen synthase kinase 3beta (GSK3beta) or casein kinase 1 or 2 (CK1/2) markedly slowed the decay of nuclear NFATc1-GFP after cessation of muscle fibre electrical stimulation, whereas inhibition of casein kinase 1delta, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase and protein kinase A had little effect. Simultaneous inhibition of GSK3beta and CK1/2 completely blocked the nuclear export of NFATc1-GFP after muscle activity. We also developed a simplified model of NFATc1 phosphorylation/dephosphorylation and nuclear fluxes, and used this model to simulate the observed time courses of nuclear NFATc1-GFP with and without NFATc1 kinase inhibition. Our results suggest that GSK3beta and CK1/2 are the major protein kinases that contribute to the removal of NFATc1 that accumulates in muscle fibre nuclei during muscle activity, and that GSK3beta and CK1/2 are responsible for phosphorylating NFATc1 in muscle nuclei in a complementary or synergistic fashion.

  14. Influence of Botulinumtoxin A on the Expression of Adult MyHC Isoforms in the Masticatory Muscles in Dystrophin-Deficient Mice (Mdx-Mice)

    PubMed Central

    Todorov, Teodor

    2016-01-01

    The most widespread animal model to investigate Duchenne muscular dystrophy is the mdx-mouse. In contrast to humans, phases of muscle degeneration are replaced by regeneration processes; hence there is only a restricted time slot for research. The aim of the study was to investigate if an intramuscular injection of BTX-A is able to break down muscle regeneration and has direct implications on the gene expression of myosin heavy chains in the corresponding treated and untreated muscles. Therefore, paralysis of the right masseter muscle was induced in adult healthy and dystrophic mice by a specific intramuscular injection of BTX-A. After 21 days the mRNA expression and protein content of MyHC isoforms of the right and left masseter, temporal, and the tongue muscle were determined using quantitative RT-PCR and Western blot technique. MyHC-IIa and MyHC-I-mRNA expression significantly increased in the paralyzed masseter muscle of control-mice, whereas MyHC-IIb and MyHC-IIx/d-mRNA were decreased. In dystrophic muscles no effect of BTX-A could be detected at the level of MyHC. This study suggests that BTX-A injection is a suitable method to simulate DMD-pathogenesis in healthy mice but further investigations are necessary to fully analyse the BTX-A effect and to generate sustained muscular atrophy in mdx-mice. PMID:27689088

  15. The effect of nitrate supplementation on muscle contraction in healthy adults.

    PubMed

    Hoon, Matthew W; Fornusek, Ché; Chapman, Phillip G; Johnson, Nathan A

    2015-01-01

    This study examined the effect of dietary supplementation with inorganic nitrate ([Formula: see text] ) on markers of contractile function in human knee extensors. In a double-blinded, randomized cross-over design, 18 (12 M) healthy participants undertook four days of supplementation with either nitrate-rich beetroot juice (NITRATE; days 1-3: 525 mg [Formula: see text], day 4: 1050 mg [Formula: see text]) or nitrate-depleted beetroot juice (PLACEBO). On the fourth day, isometric knee extension force was assessed during a series of voluntary and electrically evoked (stimulation) tests. In addition, muscular fatigue was examined in two separate continuous-stimulation (0.8 s tetanus with a 1:1 work:rest ratio for 102.4 s) fatigue tests, one with and one without blood flow restriction. There were no differences for maximum voluntary contraction, peak twitch force, half-relaxation time and the force-frequency relationship for stimulations up to 100 Hz between the NITRATE and PLACEBO trials. No differences between trials were observed in the non-restricted fatigue test, however NITRATE was found to attenuate the decline in force during the restricted test, such that the force at the 80 s mark (PLACEBO: 66 ± 11 vs. NITRATE 74 ± 9% of initial force; P = .01) and 102 s mark (PLACEBO: 47 ± 8% vs. NITRATE 55 ± 8%; P < .01) were significantly higher. These results suggest that four days of [Formula: see text] supplementation elicits peripheral responses in muscle that attenuate muscular fatigue during exhaustive exercise under hypovolemic conditions. This ergogenic action is likely attributable to improved Ca(2+) handling in the muscle, or enhanced perfusion during ischemia.

  16. DNA methylation dynamics in muscle development and disease

    PubMed Central

    Carrió, Elvira; Suelves, Mònica

    2015-01-01

    DNA methylation is an essential epigenetic modification for mammalian development and is crucial for the establishment and maintenance of cellular identity. Traditionally, DNA methylation has been considered as a permanent repressive epigenetic mark. However, the application of genome-wide approaches has allowed the analysis of DNA methylation in different genomic contexts revealing a more dynamic regulation than originally thought, since active DNA methylation and demethylation occur during cellular differentiation and tissue specification. Satellite cells are the primary stem cells in adult skeletal muscle and are responsible for postnatal muscle growth, hypertrophy, and muscle regeneration. This review outlines the published data regarding DNA methylation changes along the skeletal muscle program, in both physiological and pathological conditions, to better understand the epigenetic mechanisms that control myogenesis. PMID:25798107

  17. Jaw Dysfunction Related to Pterygoid and Masseter Muscle Dosimetry After Radiation Therapy in Children and Young Adults With Head-and-Neck Sarcomas

    SciTech Connect

    Krasin, Matthew J.; Wiese, Kristin M.; Spunt, Sheri L.; Hua, Chia-ho; Daw, Najat; Navid, Fariba; Davidoff, Andrew M.; McGregor, Lisa; Merchant, Thomas E.; Kun, Larry E.; McCrarey, Lola; and others

    2012-01-01

    Purpose: To investigate the relationship between jaw function, patient and treatment variables, and radiation dosimetry of the mandibular muscles and joints in children and young adults receiving radiation for soft-tissue and bone sarcomas. Methods and Materials: Twenty-four pediatric and young adult patients with head-and-neck sarcomas were treated on an institutional review board-approved prospective study of focal radiation therapy for local tumor control. Serial jaw depression measurements were related to radiation dosimetry delivered to the medial and lateral pterygoid muscles, masseter muscles, and temporomandibular joints to generate mathematical models of jaw function. Results: Baseline jaw depression was only influenced by the degree of surgical resection. In the first 12 weeks from initiation of radiation, surgical procedures greater than a biopsy, administration of cyclophosphamide containing chemotherapy regimes, and large gross tumor volumes adversely affected jaw depression. Increasing dose to the pterygoid and masseter muscles above 40 Gy predicted loss of jaw function over the full course of follow-up. Conclusions: Clinical and treatment factors are related to initial and subsequent jaw dysfunction. Understanding these complex interactions and the affect of specific radiation doses may help reduce the risk for jaw dysfunction in future children and young adults undergoing radiation therapy for the management of soft-tissue and bone sarcomas.

  18. Regional thermal specialisation in a mammal: temperature affects power output of core muscle more than that of peripheral muscle in adult mice (Mus musculus).

    PubMed

    James, Rob S; Tallis, Jason; Angilletta, Michael J

    2015-01-01

    In endotherms, such as mammals and birds, internal organs can specialise to function within a narrow thermal range. Consequently, these organs should become more sensitive to changes in body temperature. Yet, organs at the periphery of the body still experience considerable fluctuations in temperature, which could select for lower thermal sensitivity. We hypothesised that the performance of soleus muscle taken from the leg would depend less on temperature than would the performance of diaphragm muscle taken from the body core. Soleus and diaphragm muscles were isolated from mice and subjected to isometric and work-loop studies to analyse mechanical performance at temperatures between 15 and 40 °C. Across this thermal range, soleus muscle took longer to generate isometric force and longer to relax, and tended to produce greater normalised maximal force (stress) than did diaphragm muscle. The time required to produce half of maximal force during isometric tetanus and the time required to relax half of maximal force were both more sensitive to temperature in soleus than they were in diaphragm. However, thermal sensitivities of maximal force during isometric tetani were similar for both muscles. Consistent with our hypothesis, power output (the product of speed and force) was greater in magnitude and more thermally sensitive in diaphragm than it was in soleus. Our findings, when combined with previous observations of muscles from regionally endothermic fish, suggest that endothermy influences the thermal sensitivities of power output in core and peripheral muscles.

  19. Factors associated with skeletal muscle mass, sarcopenia, and sarcopenic obesity in older adults: a multi‐continent study

    PubMed Central

    Koyanagi, Ai; Olaya, Beatriz; Ayuso‐Mateos, Jose Luis; Miret, Marta; Chatterji, Somnath; Tobiasz‐Adamczyk, Beata; Koskinen, Seppo; Leonardi, Matilde; Haro, Josep Maria

    2015-01-01

    Abstract Background The aim of this study was to evaluate the factors associated with low skeletal muscle mass (SMM), sarcopenia, and sarcopenic obesity using nationally representative samples of people aged ≥65 years from diverse geographical regions of the world. Methods Data were available for 18 363 people aged ≥65 years who participated in the Collaborative Research on Ageing in Europe survey conducted in Finland, Poland, and Spain, and the World Health Organization Study on global AGEing and adult health survey conducted in China, Ghana, India, Mexico, Russia, and South Africa, between 2007 and 2012. A skeletal muscle mass index (SMI) was created to reflect SMM. SMM, SMI, and percent body fat (%BF) were calculated with specific indirect population formulas. These estimates were based on age, sex, weight, height, and race. Sarcopenia and sarcopenic obesity were defined with specific cut‐offs. Results The prevalence of sarcopenia ranged from 12.6% (Poland) to 17.5% (India), and that of sarcopenic obesity ranged from 1.3% (India) to 11.0% (Spain). Higher %BF was associated with lower SMM in all countries, and with sarcopenia in five countries (p < 0.001). Compared to high levels of physical activity, low levels were related with higher odds for sarcopenia [OR 1.36 (95%CI 1.11–1.67)] and sarcopenic obesity [OR 1.80 (95%CI 1.23–2.64)] in the overall sample. Also, a dose‐dependent association between higher numbers of chronic diseases and sarcopenic obesity was observed. Conclusions Physical activity and body composition changes such as high %BF are key factors for the prevention of sarcopenia syndrome. PMID:27239412

  20. Effects of verapamil, sodium nitroprusside, tetrodotoxin and caffeine on the electrical transmural stimulation induced contraction in the reticular groove smooth muscle of adult cattle.

    PubMed

    San Andrés, M D; González, F; Encinas, T; de Vicente, M L; Rodríguez, C; San Andrés, M I

    1994-11-01

    The effect of electrical transmural stimulation (ETS) on smooth muscle strips in the floor of reticular groove of adult cattle was studied. The mechanical activity of the muscle strips was recorded isometrically. ETS (4 ms, 5 s, supramaximal voltage) caused frequency dependent (2-30 Hz) contractions of this smooth muscle. An increase in cytoplasmatic free calcium concentration can be achieved by release of the cation from intracellular store sites or by an influx of extracellular Ca2+ through calcium channels. The contractile response of the muscle strips was inhibited about 66% when it was incubated in a calcium-free EGTA-containing solution. The excitatory effect of ETS was not antagonized by verapamil (10(-6) mol/l), sodium nitroprusside (10(-6) mol/l) or tetrodotoxin (10(-6) mol/l). The electrically-evoked contraction was inhibited strongly (92%) by caffeine (30 mmol/l). The contractions of the smooth muscle from the reticular groove smooth muscle are dependent on the concentration of free calcium in the cell cytosol. This response was intracellular Ca2+ ion dependent.

  1. Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells

    NASA Technical Reports Server (NTRS)

    Kato, S.; Koide, M.; Cooper, G. 4th; Zile, M. R.

    1996-01-01

    It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

  2. Nutritional status induces divergent variations of GLUT4 protein content, but not lipoprotein lipase activity, between adipose tissues and muscles in adult cattle.

    PubMed

    Bonnet, Muriel; Faulconnier, Yannick; Hocquette, Jean-François; Bocquier, François; Leroux, Christine; Martin, Patrice; Chilliard, Yves

    2004-10-01

    Metabolic adaptations to variations in food supply are incompletely understood in ruminant animal adipose tissue (AT) and muscle. To explore this, we studied lipid metabolism and glucose transport potential in one internal and one external AT, as well as in one oxidative and one glycolytic muscle from control, 7 d underfed and 21 d refed adult cows. Refeeding increased (+79 to +307 %) the activities of enzymes involved in de novo lipogenesis (fatty acid synthase, malic enzyme, glucose-6-phosphate dehydrogenase) in perirenal and subcutaneous AT; underfeeding did not modify these variables. Underfeeding decreased the activities of lipoprotein lipase (LPL) in perirenal AT (-70 %) and cardiac muscle (-67 %), but did not modify the activities in subcutaneous AT and longissimus thoracis. Refeeding increased LPL activities in all tissues (+40 to +553 %) to levels comparable with (cardiac muscle) or greater than (AT, longissimus thoracis) those observed in control cows. Such variations in perirenal and cardiac muscle LPL activities did not result from variations in LPL mRNA levels, but suggest a post-transcriptional regulation of LPL in these nutritional conditions. Underfeeding did not modify GLUT4 contents in perirenal AT and muscles, while refeeding increased it only in perirenal AT (+250 %). Our present results contrast with previous results in rats, where LPL is regulated in opposite directions in AT and muscles, and GLUT4 is generally increased by fasting and decreased by refeeding in skeletal muscles. The present results highlight the bovine specificity of the response, which probably arises in part from peculiarities of ruminant animals for nutrient digestion and absorption.

  3. The effects of temperature reduction on gene expression and oxidative stress in skeletal muscle from adult zebrafish.

    PubMed

    Malek, Renae L; Sajadi, Hedieh; Abraham, Joseph; Grundy, Martin A; Gerhard, Glenn S

    2004-07-01

    Longevity is inversely proportional to ambient temperature in ectothermic organisms such as fish. However, the mechanism by which reducing temperature over a physiological range increases life span is not known and available data are derived primarily from invertebrates. With a rodent-like longevity and abundant biological resources, the zebrafish is an ideal vertebrate ectothermic model in which to investigate this phenomenon. As an initial approach, the effects of a year-long 10 degrees C reduction in water temperature on global gene expression in tail skeletal muscle from adult zebrafish were determined using an oligonucleotide microarray representing 15,512 genes. Expression levels for approximately 600 genes were up-regulated by 1.7-fold or greater by the reduction in temperature, while a similar number of transcripts were down regulated by more than 1.7-fold. Using gene ontology (GO) classifications for molecular function, two functional groups, "oxygen and reactive oxygen species metabolism" and "response to oxidative stress," were found to be overrepresented among up-regulated genes. Transcripts levels for the genes in these two categories were increased by temperature reduction (TR). However, temperature reduction did not suppress lipid peroxidation potential, protein carbonyl content, or 8-oxoguanine level. Additional studies will be required to further delineate the role of altered gene expression and oxidative stress on the longevity-promoting effects of temperature reduction.

  4. Muscle-invasive bladder cancer in a young adult: a case report and a review of the literature.

    PubMed

    Nabbout, Philippe; Eldefrawy, Ahmed; Engles, C Dirk; Culkin, Daniel J; Slobodov, Gennady

    2013-01-01

    The peak incidence of bladder cancer (BC) is in the sixth decade of life. Muscle-invasive bladder cancer (MIBC) in young adults is extremely rare. We report a case of MIBC in a 28-year-old smoking male patient. The patient presented with hematuria and flank pain for which he underwent a computerized tomography (CT) scan of the abdomen and pelvis with and without contrast. The CT scan showed a 6 cm mass on the left side of the trigone extending to the left urteric orifice and left hydronephrosis, but no lymphadenopathy was noted. The patient then underwent a left nephrostomy tube placement followed by trans-urethral resection of bladder tumor (TURBT). The tumor involved both ureteric orifices and extended to the prostatic urethra. Complete resection was not feasible. Pathology showed high-grade T1 urothelial carcinoma. CT scan of the chest showed no distant lung metastasis. The patient then elected to undergo radical cystectomy with ileal conduit urinary diversion. Final pathology revealed T2a N0 urothelial carcinoma of the bladder. Our aim is to present our experience and review the literature for the natural history and oncological and quality of life outcomes of urothelial carcinoma of the bladder in young patients.

  5. Polymyositis - adult

    MedlinePlus

    ... rash is a sign of a similar condition, dermatomyositis . Common symptoms include: Muscle weakness in the shoulders ... in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. ...

  6. Sonic hedgehog promotes proliferation and differentiation of adult muscle cells: Involvement of MAPK/ERK and PI3K/Akt pathways.

    PubMed

    Elia, Dafna; Madhala, Dorit; Ardon, Eti; Reshef, Ram; Halevy, Orna

    2007-09-01

    Sonic hedgehog (Shh) has been reported to act as a mitogen and survival factor for muscle satellite cells. However, its role in their differentiation remains ambiguous. Here, we provide evidence that Shh promotes the proliferation and differentiation of primary cultures of chicken adult myoblasts (also termed satellite cells) and mouse myogenic C2 cells. These effects are reversed by cyclopamine, a specific chemical inhibitor of the Shh pathway. In addition, we show that Shh and its downstream molecules are expressed in adult myoblast cultures and localize adjacent to Pax7 in muscle sections. These gene expressions are regulated during postnatal muscle growth in chicks. Most importantly, we report that Shh induces MAPK/ERK and phosphoinositide 3-kinase (PI3K)-dependent Akt phosphorylation and that activation of both signaling pathways is essential for Shh's signaling in muscle cells. However, the effect of Shh on Akt phosphorylation is more robust than that on MAPK/ERK, and data suggest that Shh influences these pathways in a manner similar to IGF-I. By exploiting specific chemical inhibitors of the MAPK/ERK and PI3K/Akt signaling pathways, UO126 and Ly294002, respectively, we demonstrate that Shh-induced Akt phosphorylation, but not that of MAPK/ERK, is required for its promotive effects on muscle cell proliferation and differentiation. Taken together, we suggest that Shh acts in an autocrinic manner in adult myoblasts, and provide first evidence of a role for PI3K/Akt in Shh signaling during myoblast differentiation.

  7. Influence of Nrf2 activators on subcellular skeletal muscle protein and DNA synthesis rates after 6 weeks of milk protein feeding in older adults.

    PubMed

    Konopka, Adam R; Laurin, Jaime L; Musci, Robert V; Wolff, Christopher A; Reid, Justin J; Biela, Laurie M; Zhang, Qian; Peelor, Fredrick F; Melby, Christopher L; Hamilton, Karyn L; Miller, Benjamin F

    2017-03-10

    In older adults, chronic oxidative and inflammatory stresses are associated with an impaired increase in skeletal muscle protein synthesis after acute anabolic stimuli. Conjugated linoleic acid (CLA) and Protandim have been shown to activate nuclear factor erythroid-derived 2-like 2 (Nrf2), a transcription factor for the antioxidant response element and anti-inflammatory pathways. This study tested the hypothesis that compared to a placebo control (CON), CLA and Protandim would increase skeletal muscle subcellular protein (myofibrillar, mitochondrial, cytoplasmic) and DNA synthesis in older adults after 6 weeks of milk protein feeding. CLA decreased oxidative stress and skeletal muscle oxidative damage with a trend to increase messenger RNA (mRNA) expression of a Nrf2 target, NAD(P)H dehydrogenase quinone 1 (NQO1). However, CLA did not influence other Nrf2 targets (heme oxygenase-1 (HO-1), glutathione peroxidase 1 (Gpx1)) or protein or DNA synthesis. Conversely, Protandim increased HO-1 protein content but not the mRNA expression of downstream Nrf2 targets, oxidative stress, or skeletal muscle oxidative damage. Rates of myofibrillar protein synthesis were maintained despite lower mitochondrial and cytoplasmic protein syntheses after Protandim versus CON. Similarly, DNA synthesis was non-significantly lower after Protandim compared to CON. After Protandim, the ratio of protein to DNA synthesis tended to be greater in the myofibrillar fraction and maintained in the mitochondrial and cytoplasmic fractions, emphasizing the importance of measuring both protein and DNA synthesis to gain insight into proteostasis. Overall, these data suggest that Protandim may enhance proteostatic mechanisms of skeletal muscle contractile proteins after 6 weeks of milk protein feeding in older adults.

  8. Effect of Wiihabilitation on strength ratio of ankle muscles in adults

    PubMed Central

    Khalil, Aya A.; Mohamed, Ghada A.; El Rahman, Soheir M. Abd; Elhafez, Salam M.; Nassif, Nagui S.

    2016-01-01

    [Purpose] This study was conducted to investigate the effect of Wiihabilitation on the ankle dorsiflexion/plantar flexion strength ratio in adults. [Subjects and Methods] Thirty-two healthy male volunteers were randomly assigned to two equal groups (experimental and control). Participants in the experimental group received a Wiihabilitation training program for six weeks. Data were collected using a Biodex system 3 Isokinetic dynamometer. Peak torques of the dorsiflexors and plantar flexors were measured at an angular velocity of 60°/sec which in turn were used to derive the ankle dorsiflexion/plantar flexion strength ratio. [Results] The mean values of the ankle dorsiflexion/plantar flexion strength ratio decreased significantly between before and after the training in the experimental group, meanwhile there was no significant difference between before and after the training period in the control group . [Conclusion] Wiihabilitation has an impact on the ankle dorsiflexion/plantar flexion strength ratio, so it can be considered an effective training tool in terms of the ankle strength ratio. Thus, it could be recommended for both prevention and rehabilitation of ankle instability patients. PMID:27821951

  9. Postnatal exposure to a high-carbohydrate diet interferes epigenetically with thyroid hormone receptor induction of the adult male rat skeletal muscle glucose transporter isoform 4 expression.

    PubMed

    Raychaudhuri, Nupur; Thamotharan, Shanthie; Srinivasan, Malathi; Mahmood, Saleh; Patel, Mulchand S; Devaskar, Sherin U

    2014-10-01

    Early life nutritional intervention causes adult-onset insulin resistance and obesity in rats. Thyroid hormone receptor (TR), in turn, transcriptionally enhances skeletal muscle Glut4 expression. We tested the hypothesis that reduced circulating thyroid-stimulating hormone and T4 concentrations encountered in postnatal (PN4-PN24) high-carbohydrate (HC) milk formula-fed versus the mother-fed controls (MF) would epigenetically interfere with TR induction of adult (100 days) male rat skeletal muscle Glut4 expression, thereby providing a molecular mechanism mediating insulin resistance. We observed increased DNA methylation of the CpG island with enhanced recruitment of Dnmt3a, Dnmt3b and MeCP2 in the glut4 promoter region along with reduced acetylation of histone (H)2A.Z and H4 particularly at the H4.lysine (K)16 residue, which was predominantly mediated by histone deacetylase 4 (HDAC4). This was followed by enhanced recruitment of heterochromatin protein 1β to the glut4 promoter with increased Suv39H1 methylase concentrations. These changes reduced TR binding of the T3 response element of the glut4 gene (TREs; -473 to -450 bp) detected qualitatively in vivo (electromobility shift assay) and quantified ex vivo (chromatin immunoprecipitation). In addition, the recruitment of steroid receptor coactivator and CREB-binding protein to the glut4 promoter-protein complex was reduced. Co-immunoprecipitation experiments confirmed the interaction between TR and CBP to be reduced and HDAC4 to be enhanced in HC versus MF groups. These molecular changes were associated with diminished skeletal muscle Glut4 mRNA and protein concentrations. We conclude that early postnatal exposure to HC diet epigenetically reduced TR induction of adult male skeletal muscle Glut4 expression, uncovering novel molecular mechanisms contributing to adult insulin resistance and obesity.

  10. Muscle disuse alters skeletal muscle contractile function at the molecular and cellular levels in older adult humans in a sex-specific manner

    PubMed Central

    Callahan, Damien M; Miller, Mark S; Sweeny, Andrew P; Tourville, Timothy W; Slauterbeck, James R; Savage, Patrick D; Maugan, David W; Ades, Philip A; Beynnon, Bruce D; Toth, Michael J

    2014-01-01

    Physical inactivity that accompanies ageing and disease may hasten disability by reducing skeletal muscle contractility. To characterize skeletal muscle functional adaptations to muscle disuse, we compared contractile performance at the molecular, cellular and whole-muscle levels in healthy active older men and women (n = 15) and inactive older men and women with advanced-stage, symptomatic knee osteoarthritis (OA) (n = 16). OA patients showed reduced (P < 0.01) knee extensor function. At the cellular level, single muscle fibre force production was reduced in OA patients in myosin heavy chain (MHC) I and IIA fibres (both P < 0.05) and differences in IIA fibres persisted after adjustments for fibre cross-sectional area (P < 0.05). Although no group differences in contractile velocity or power output were found for any fibre type, sex was found to modify the effect of OA, with a reduction in MHC IIA power output and a trend towards reduced shortening velocity in women, but increases in both variables in men (P < 0.05 and P = 0.07, respectively). At the molecular level, these adaptations in MHC IIA fibre function were explained by sex-specific differences (P ≤ 0.05) in myosin–actin cross-bridge kinetics. Additionally, cross-bridge kinetics were slowed in MHC I fibres in OA patients (P < 0.01), attributable entirely to reductions in women with knee OA (P < 0.05), a phenotype that could be reproduced in vitro by chemical modification of protein thiol residues. Our results identify molecular and cellular functional adaptations in skeletal muscle that may contribute to reduced physical function with knee OA-associated muscle disuse, with sex-specific differences that may explain a greater disposition towards disability in women. PMID:25038243

  11. Identification of the essential protein domains for Mib2 function during the development of the Drosophila larval musculature and adult flight muscles

    PubMed Central

    Domsch, Katrin; Acs, Andreas; Obermeier, Claudia; Nguyen, Hanh T.

    2017-01-01

    The proper differentiation and maintenance of myofibers is fundamental to a functional musculature. Disruption of numerous mostly structural factors leads to perturbations of these processes. Among the limited number of known regulatory factors for these processes is Mind bomb2 (Mib2), a muscle-associated E3 ubiquitin ligase, which was previously established to be required for maintaining the integrity of larval muscles. In this study, we have examined the mechanistic aspects of Mib2 function by performing a detailed functional dissection of the Mib2 protein. We show that the ankyrin repeats, in its entirety, and the hitherto uncharacterized Mib-specific domains (MIB), are important for the major function of Mib2 in skeletal and visceral muscles in the Drosophila embryo. Furthermore, we characterize novel mib2 alleles that have arisen from a forward genetic screen aimed at identifying regulators of myogenesis. Two of these alleles are viable, but flightless hypomorphic mib2 mutants, and harbor missense mutations in the MIB domain and RING finger, respectively. Functional analysis of these new alleles, including in vivo imaging, demonstrates that Mib2 plays an additional important role in the development of adult thorax muscles, particularly in maintaining the larval templates for the dorsal longitudinal indirect flight muscles during metamorphosis. PMID:28282454

  12. Core Muscle Activity during TRX Suspension Exercises with and without Kinesiology Taping in Adults with Chronic Low Back Pain: Implications for Rehabilitation

    PubMed Central

    Fong, Shirley S. M.; Tam, Y. T.; Macfarlane, Duncan J.; Ng, Shamay S. M.; Bae, Young-Hyeon; Chan, Eleanor W. Y.; Guo, X.

    2015-01-01

    This study aimed to examine the effects of kinesiology taping (KT) and different TRX suspension workouts on the amplitude of electromyographic (EMG) activity in the core muscles among people with chronic low back pain (LBP). Each participant (total n = 21) was exposed to two KT conditions: no taping and taping, while performing four TRX suspension exercises: (1) hamstring curl, (2) hip abduction in plank, (3) chest press, and (4) 45-degree row. Right transversus abdominis/internal oblique (TrAIO), rectus abdominis (RA), external oblique (EO), and superficial lumbar multifidus (LMF) activity was recorded with surface EMG and expressed as a percentage of the EMG amplitude recorded during a maximal voluntary isometric contraction of the respective muscles. Hip abduction in plank increased TrAIO, RA, and LMF EMG amplitude compared with other TRX positions (P < 0.008). Only the hamstring curl was effective in inducing a high EMG amplitude of LMF (P < 0.001). No significant difference in EMG magnitude was found between the taping and no taping conditions overall (P > 0.05). Hip abduction in plank most effectively activated abdominal muscles, whereas the hamstring curl most effectively activated the paraspinal muscles. Applying KT conferred no immediate benefits in improving the core muscle activation during TRX training in adults with chronic LBP. PMID:26185520

  13. The effects of performing a one-legged bridge with hip abduction and use of a sling on trunk and lower extremity muscle activation in healthy adults

    PubMed Central

    Choi, Kyuju; Bak, Jongwoo; Cho, Minkwon; Chung, Yijung

    2016-01-01

    [Purpose] This study investigated the changes in the muscle activities of the trunk and lower limbs of healthy adults during a one-legged bridge exercise using a sling, and with the addition of hip abduction. [Subjects and Methods] Twenty-seven healthy individuals participated in this study (14 males and 13 females). The participants were instructed to perform the bridge exercises under five different conditions. Trunk and lower limb muscle activation of the erector spinae (ES), external oblique (EO), gluteus maximus (GM), and biceps femoris (BF) was measured using surface electromyography. Data analysis was performed using the mean scores of three trials performed under each condition. [Results] There was a significant increase in bilateral EO and contralateral GM with the one-legged bridge compared with the one-legged bridge with sling exercise. Muscle activation of the ipsilateral GM and BF was significantly less during the one-legged bridge exercise compared to the one-legged bridge with sling exercise, and was significantly greater during the one-legged bridge with hip abduction compared to the one-legged bridge exercise. The muscle activation of the contralateral GM and BF was significantly greater with the one-legged bridge with hip abduction compared to the general bridge exercise. [Conclusion] With the one-legged bridge with hip abduction, the ipsilateral EO, GM and BF muscle activities were significantly greater than those of the one-legged bridge exercise. The muscle activation of all trunk and contralateral lower extremity muscles increased with the bridge with sling exercises compared with general bridge exercises. PMID:27799708

  14. Possible Muscle Repair in the Human Cardiovascular System.

    PubMed

    Sommese, Linda; Zullo, Alberto; Schiano, Concetta; Mancini, Francesco P; Napoli, Claudio

    2017-04-01

    The regenerative potential of tissues and organs could promote survival, extended lifespan and healthy life in multicellular organisms. Niches of adult stemness are widely distributed and lead to the anatomical and functional regeneration of the damaged organ. Conversely, muscular regeneration in mammals, and humans in particular, is very limited and not a single piece of muscle can fully regrow after a severe injury. Therefore, muscle repair after myocardial infarction is still a chimera. Recently, it has been recognized that epigenetics could play a role in tissue regrowth since it guarantees the maintenance of cellular identity in differentiated cells and, therefore, the stability of organs and tissues. The removal of these locks can shift a specific cell identity back to the stem-like one. Given the gradual loss of tissue renewal potential in the course of evolution, in the last few years many different attempts to retrieve such potential by means of cell therapy approaches have been performed in experimental models. Here we review pathways and mechanisms involved in the in vivo repair of cardiovascular muscle tissues in humans. Moreover, we address the ongoing research on mammalian cardiac muscle repair based on adult stem cell transplantation and pro-regenerative factor delivery. This latter issue, involving genetic manipulations of adult cells, paves the way for developing possible therapeutic strategies in the field of cardiovascular muscle repair.

  15. Deletion of MLIP (Muscle-enriched A-type Lamin-interacting Protein) Leads to Cardiac Hyperactivation of Akt/Mammalian Target of Rapamycin (mTOR) and Impaired Cardiac Adaptation*

    PubMed Central

    Cattin, Marie-Elodie; Wang, Jessica; Weldrick, Jonathan J.; Roeske, Cassandra L.; Mak, Esther; Thorn, Stephanie L.; DaSilva, Jean N.; Wang, Yibin; Lusis, Aldon J.; Burgon, Patrick G.

    2015-01-01

    Aging and diseases generally result from tissue inability to maintain homeostasis through adaptation. The adult heart is particularly vulnerable to disequilibrium in homeostasis because its regenerative abilities are limited. Here, we report that MLIP (muscle enriched A-type lamin-interacting protein), a unique protein of unknown function, is required for proper cardiac adaptation. Mlip−/− mice exhibited normal cardiac function despite myocardial metabolic abnormalities and cardiac-specific overactivation of Akt/mTOR pathways. Cardiac-specific MLIP overexpression led to an inhibition of Akt/mTOR, providing evidence of a direct impact of MLIP on these key signaling pathways. Mlip−/− hearts showed an impaired capacity to adapt to stress (isoproterenol-induced hypertrophy), likely because of deregulated Akt/mTOR activity. Genome-wide association studies showed a genetic association between Mlip and early response to cardiac stress, supporting the role of MLIP in cardiac adaptation. Together, these results revealed that MLIP is required for normal myocardial adaptation to stress through integrated regulation of the Akt/mTOR pathways. PMID:26359501

  16. No major sex differences in muscle protein synthesis rates in the postabsorptive state and during hyperinsulinemia-hyperaminoacidemia in middle-aged adults.

    PubMed

    Smith, Gordon I; Atherton, Philip; Reeds, Dominic N; Mohammed, B Selma; Jaffery, Hadia; Rankin, Debbie; Rennie, Michael J; Mittendorfer, Bettina

    2009-10-01

    Men have more muscle than women, but most studies evaluating sex differences in muscle protein metabolism have been unable to discern sexual dimorphism in basal muscle protein turnover rates in young and middle-aged adults. We hypothesized that the anabolic response to nutritional stimuli (i.e., amino acids and insulin) would be greater in young/middle-aged men than women. We therefore measured the rates of muscle protein synthesis (MPS) in 16 healthy individuals [8 men and 8 women, matched for age (mean +/- SE: 37.7 +/- 1.5 yr) and body mass index (25.2 +/- 0.7 kg/m2)] after an overnight fast (plasma insulin approximately 5 microU/ml and plasma phenylalanine approximately 60 microM) and during a hyperinsulinemic-hyperaminoacidemic-euglycemic clamp (plasma insulin approximately 28 microU/ml; plasma phenylalanine approximately 110 microM; plasma glucose approximately 5.4 mM). The rates of MPS were not different between men and women (ANOVA main effect for sex; P = 0.49). During the clamp, the rate of MPS increased by approximately 50% (P = 0.003) with no difference in the increases from basal values between men and women (+0.019 +/- 0.004 vs. +0.018 +/- 0.010%/h, respectively; P = 0.93). There were also no differences between men and women in the basal concentrations of muscle phosphorylated Akt(Ser473), Akt(Thr308), mTOR(Ser2448), and p70s6k(Thr389) or in the hyperinsulinemia-hyperaminoacidemia-induced increases in phosphorylation of those signaling elements (P > or = 0.25). We conclude that there are no major differences in the rate of MPS and its intracellular control during basal conditions and during hyperinsulinemia-hyperaminoacidema between young and middle-aged adult men and women.

  17. No major sex differences in muscle protein synthesis rates in the postabsorptive state and during hyperinsulinemia-hyperaminoacidemia in middle-aged adults

    PubMed Central

    Smith, Gordon I.; Atherton, Philip; Reeds, Dominic N.; Mohammed, B. Selma; Jaffery, Hadia; Rankin, Debbie; Rennie, Michael J.

    2009-01-01

    Men have more muscle than women, but most studies evaluating sex differences in muscle protein metabolism have been unable to discern sexual dimorphism in basal muscle protein turnover rates in young and middle-aged adults. We hypothesized that the anabolic response to nutritional stimuli (i.e., amino acids and insulin) would be greater in young/middle-aged men than women. We therefore measured the rates of muscle protein synthesis (MPS) in 16 healthy individuals [8 men and 8 women, matched for age (mean ± SE: 37.7 ± 1.5 yr) and body mass index (25.2 ± 0.7 kg/m2)] after an overnight fast (plasma insulin ∼5 μU/ml and plasma phenylalanine ∼60 μM) and during a hyperinsulinemic-hyperaminoacidemic-euglycemic clamp (plasma insulin ∼28 μU/ml; plasma phenylalanine ∼110 μM; plasma glucose ∼5.4 mM). The rates of MPS were not different between men and women (ANOVA main effect for sex; P = 0.49). During the clamp, the rate of MPS increased by ∼50% (P = 0.003) with no difference in the increases from basal values between men and women (+0.019 ± 0.004 vs. +0.018 ± 0.010%/h, respectively; P = 0.93). There were also no differences between men and women in the basal concentrations of muscle phosphorylated AktSer473, AktThr308, mTORSer2448, and p70s6kThr389 or in the hyperinsulinemia-hyperaminoacidemia-induced increases in phosphorylation of those signaling elements (P ≥ 0.25). We conclude that there are no major differences in the rate of MPS and its intracellular control during basal conditions and during hyperinsulinemia-hyperaminoacidema between young and middle-aged adult men and women. PMID:19644030

  18. Single adult rabbit and rat cardiac myocytes retain the Ca2+- and species-dependent systolic and diastolic contractile properties of intact muscle

    PubMed Central

    1986-01-01

    The systolic and diastolic properties of single myocytes and intact papillary muscles isolated from hearts of adult rats and rabbits were examined at 37 degrees C over a range of stimulation frequencies and bathing [Ca2+]o (Cao). In both rabbit myocytes and intact muscles bathed in 1 mM Cao, increasing the frequency of stimulation from 6 to 120 min-1 resulted in a positive staircase of twitch performance. During stimulation at 2 min-1, twitch performance also increased with increases in Cao up to 20 mM. In the absence of stimulation, both rabbit myocytes and muscles were completely quiescent in less than 15 mM Cao. Further increases in Cao caused the appearance of spontaneous asynchronous contractile waves in myocytes and in intact muscles caused scattered light intensity fluctuations (SLIF), which were previously demonstrated to be caused by Ca2+-dependent spontaneous contractile waves. In contrast to rabbit preparations, intact rat papillary muscles exhibited SLIF in 1.0 mM Cao. Two populations of rat myocytes were observed in 1 mM Cao: approximately 85% of unstimulated cells exhibited low-frequency (3-4 min-1) spontaneous contractile waves, whereas 15%, during a 1-min observation period, were quiescent. In a given Cao, the contractile wave frequency in myocytes and SLIF in intact muscles were constant for long periods of time. In both intact rat muscles and myocytes with spontaneous waves, in 1 mM Cao, increasing the frequency of stimulation from 6 to 120 min-1 resulted, on the average, in a 65% reduction in steady state twitch amplitude. Of the rat myocytes that did not manifest waves, some had a positive, some had a flat, and some had a negative staircase; the average steady state twitch amplitude of these cells during stimulation at 120 min-1 was 30% greater than that at 6 min-1. In contrast to rabbit preparations, twitch performance during stimulation at 2 min-1 saturated at 1.5 mM Cao in both intact rat muscles and in the myocytes with spontaneous waves. We

  19. Enobosarm (GTx-024) Modulates Adult Skeletal Muscle Mass Independently of the Androgen Receptor in the Satellite Cell Lineage.

    PubMed

    Dubois, Vanessa; Simitsidellis, Ioannis; Laurent, Michaël R; Jardi, Ferran; Saunders, Philippa T K; Vanderschueren, Dirk; Claessens, Frank

    2015-12-01

    Androgens increase skeletal muscle mass, but their clinical use is hampered by a lack of tissue selectivity and subsequent side effects. Selective androgen receptor modulators elicit muscle-anabolic effects while only sparingly affecting reproductive tissues. The selective androgen receptor modulator, GTx-024 (enobosarm), is being investigated for cancer cachexia, sarcopenia, and muscle wasting diseases. Here we investigate the role of muscle androgen receptor (AR) in the anabolic effect of GTx-024. In mice lacking AR in the satellite cell lineage (satARKO), the weight of the androgen-sensitive levator ani muscle was lower but was decreased further upon orchidectomy. GTx-024 was as effective as DHT in restoring levator ani weights to sham levels. Expression of the muscle-specific, androgen-responsive genes S-adenosylmethionine decarboxylase and myostatin was decreased by orchidectomy and restored by GTx-024 and DHT in control mice, whereas the expression was low and unaffected by androgen status in satARKO. In contrast, insulin-like growth factor 1Ea expression was not different between satARKO and control muscle, decreased upon castration, and was restored by DHT and GTx-024 in both genotypes. These data indicate that GTx-024 does not selectively modulate AR in the satellite cell lineage and that cells outside this lineage remain androgen responsive in satARKO muscle. Indeed, residual AR-positive cells were present in satARKO muscle, coexpressing the fibroblast-lineage marker vimentin. AR positive, muscle-resident fibroblasts could therefore be involved in the indirect effects of androgens on muscle. In conclusion, both DHT and GTx-024 target AR pathways in the satellite cell lineage, but cells outside this lineage also contribute to the anabolic effects of androgens.

  20. Elevated Serum Uric Acid Is Associated with Greater Bone Mineral Density and Skeletal Muscle Mass in Middle-Aged and Older Adults

    PubMed Central

    He, Juan; Wang, Chen; Qiu, Rui; Chen, Yu-ming

    2016-01-01

    Background and objective Previous studies have suggested a positive link between serum uric acid (UA) and bone mineral density (BMD). In this study, we re-examined the association between UA and BMD and further explored whether this was mediated by skeletal muscle mass in a general Chinese population. Method This community-based cross-sectional study was conducted among 3079 (963 men and 2116 women) Chinese adults aged 40–75 years. Face-to-face interviews and laboratory analyses were performed to determine serum UA and various covariates. Dual-energy X-ray absorptiometry was used to assess the BMD and appendicular skeletal muscle mass. The skeletal muscle mass index (SMI = ASM/Height2, kg/m2) for the total limbs, arms, and legs was then calculated. Results The serum UA was graded and, in general, was significantly and positively associated with the BMD and muscle mass, after adjustment for multiple covariates in the total sample. Compared with participants in lowest quartile of UA, those participants in highest quartile showed a 2.3%(whole body), 4.1%(lumbar spine), 2.4%(total hip), and 2.0% (femoral neck) greater BMDs. The mean SMIs in the highest (vs. lowest) quartile increased by 2.7% (total), 2.5% (arm), 2.7% (leg) respectively. In addition, path analysis suggested that the favorable association between UA and BMD might be mediated by increasing SMI. Conclusion The elevated serum UA was associated with a higher BMD and a greater muscle mass in a middle-aged and elderly Chinese population and the UA-BMD association was partly mediated by muscle mass. PMID:27144737

  1. Determination of malachite green residues in the eggs, fry, and adult muscle-tissue of rainbow-trout (Oncorhynchus-mykiss)

    USGS Publications Warehouse

    Allen, John L.; Gofus, J.E.; Meinertz, Jeffery R.

    1994-01-01

    Malachite green, an effective antifungal therapeutant used in fish culture, is a known teratogen. We developed a method to simultaneously detect both the chromatic and leuco forms of malachite green residues in the eggs, fry, and adult muscle tissue of rainbow trout (oncorhynchus mykiss). Homogenates of these tissues were fortified with [c-14] malachite green chloride and extracted with 1% (v/v) acetic acid in acetonitrile or in methanol. The extracts were partitioned with chloroform, dried, redissolved in mobile phase, and analyzed by liquid chromatography (lc) with postcolumn oxidation of leuco malachite green to the chromatic form. Lc fractions were collected every 30 s for quantitation by scintillation counting. Recoveries of total [c-14] malachite green chloride residue were 85 and 98% in eggs fortified with labeled malachite green at concentrations of 0.5 And 1.00 Mug/g, respectively; 68% in fry similarly fortified at a concentration of 0.65 Mug/g; and 66% in muscle homogenate similarly fortified at a level of 1.00 Mug/g. The method was tested under operational conditions by exposing adult rainbow trout to 1.00 Mg/l [c-14] malachite green chloride bath for 1 h. Muscle samples analyzed by sample oxidation and scintillation counting contained 1.3 And 0.5 Mug/g total malachite green chloride residues immediately after exposure and after a 5-day withdrawal period, respectively.

  2. Eccentric contraction-induced injury to type I, IIa, and IIa/IIx muscle fibers of elderly adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Muscles of old laboratory rodents experience exaggerated force losses after eccentric contractile activity. We extended this line of inquiry to humans and investigated the influence of fiber myosin heavy chain (MHC) isoform content on the injury process. Skinned muscle fiber segments, prepared from ...

  3. Selective expression of the type 3 isoform of ryanodine receptor Ca{sup 2+} release channel (RyR3) in a subset of slow fibers in diaphragm and cephalic muscles of adult rabbits

    SciTech Connect

    Conti, Antonio; Reggiani, Carlo; Sorrentino, Vincenzo . E-mail: v.sorrentino@unisi.it

    2005-11-11

    The expression pattern of the RyR3 isoform of Ca{sup 2+} release channels was analysed by Western blot in neonatal and adult rabbit skeletal muscles. The results obtained show that the expression of the RyR3 isoform is developmentally regulated. In fact, RyR3 expression was detected in all muscles analysed at 2 and 15 days after birth while, in adult animals, it was restricted to a subset of muscles that includes diaphragm, masseter, pterygoideus, digastricus, and tongue. Interestingly, all of these muscles share a common embryonic origin being derived from the somitomeres or from the cephalic region of the embryo. Immunofluorescence analysis of rabbit skeletal muscle cross-sections showed that RyR3 staining was detected in all fibers of neonatal muscles. In contrast, in those adult muscles expressing RyR3 only a fraction of fibers was labelled. Staining of these muscles with antibodies against fast and slow myosins revealed a close correlation between expression of RyR3 and fibers expressing slow myosin isoform.

  4. The intra- and inter-rater reliabilities of lower extremity muscle strength assessment of healthy adults using a hand held dynamometer.

    PubMed

    Kim, Seong-Gil; Lee, Yun-Seob

    2015-06-01

    [Purpose] The purpose of this study was to examine the intra- and inter-rater reliabilities of lower extremity muscle strength assessment of healthy adults using hand held dynamometer. [Subjects and Methods] A total of 55 students (19 males and 36 females) in Y University in Gyeongsangnam-do, South Korea participated in this study. Lower extremity muscle strength was measured using a hand-held dynamometer (Commander Muscle Tester, JTech, USA). Flexion and extension strengths of the hip joint, the knee joint, and the ankle joint were measured. [Results] The intra-rater reliabilities were excellent (above 0.9) for the flexion and extension strengths of the ankle, knee, and hip joints. The inter-rater reliabilities were also excellent (above 0.8) for the flexion and extension strengths of the ankle, knee, and hip joint. [Conclusion] Lower extremity muscle strength assessment using a hand-held dynamometer provided consistent results when conducted by different examiners and when measured several times. Therefore, this method is a useful way of deriving objective and quantitative measurement values.

  5. Adult neuron addition to the zebra finch song motor pathway correlates with the rate and extent of recovery from botox-induced paralysis of the vocal muscles.

    PubMed

    Pytte, Carolyn; Yu, Yi-Lo; Wildstein, Sara; George, Shanu; Kirn, John R

    2011-11-23

    In adult songbirds, neurons are continually incorporated into the telencephalic nucleus HVC (used as a proper name), a premotor region necessary for the production of learned vocalizations. Previous studies have demonstrated that neuron addition to HVC is highest when song is most variable: in juveniles during song learning, in seasonally singing adults during peaks in plasticity that precede the production of new song components, or during seasonal reestablishment of a previously learned song. These findings suggest that neuron addition provides motor flexibility for the transition from a variable song to a target song. Here we test the association between the quality of song structure and HVC neuron addition by experimentally manipulating syringeal muscle control with Botox, which produces a transient partial paralysis. We show that the quality of song structure covaries with new neuron addition to HVC. Both the magnitude of song distortion and the rate of song recovery after syringeal Botox injections were correlated with the number of new neurons incorporated into HVC. We suggest that the quality of song structure is either a cause or consequence of the number of new neurons added to HVC. Birds with naturally high rates of neuron addition may have had the greatest success in recovering song. Alternatively, or in addition, new neuron survival in the song motor pathway may be regulated by the quality of song-generated feedback as song regains its original stereotyped structure. Present results are the first to show a relationship between peripheral muscle control and adult neuron addition to cortical premotor circuits.

  6. The Acute Effects of a Single Session of Expiratory Muscle Strength Training on Blood Pressure, Heart Rate, and Oxygen Saturation in Healthy Adults

    PubMed Central

    Laciuga, Helena; Davenport, Paul; Sapienza, Christine

    2012-01-01

    Expiratory muscle strength training (EMST) is a rehabilitative program that has been tested for outcomes related to respiratory muscle strength, cough, swallow, and voice function in healthy young adult, elderly individuals, and in patients with progressive neurodegenerative disease. Because EMST has been used in patient care, the associated cardiovascular responses during EMST are of importance. This study investigated the changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and oxygen saturation (SpO2) during one session of EMST in healthy, young adults as a preliminary study of device safety. Thirty-one participants completed a single session of 25 trials with the EMST device. Valsalva maneuvers were performed at the beginning and at the end of the EMST trials for task comparison. The SBP, DBP, HR, and SpO2 were recorded at the baseline and after completing the following tasks: a Valsalva maneuver, 12 trials using the EMST device, 13 trials using the EMST device, and 5 min of rest following the EMST session. A mixed linear model tested for changes across the six time points. The results indicated no significant change of SBP, DBP, HR, or SpO2 during or following the EMST trials or after performing the Valsalva maneuver. The results suggest that EMST does not elicit significant fluctuations of blood pressure, HR, and SpO2 in healthy young adults even when considering the effects of covariates on the outcomes measures. PMID:22419910

  7. Lower maternal body condition during pregnancy affects skeletal muscle structure and glut-4 protein levels but not glucose tolerance in mature adult sheep.

    PubMed

    Costello, Paula M; Hollis, Lisa J; Cripps, Roselle L; Bearpark, Natasha; Patel, Harnish P; Sayer, Avan Aihie; Cooper, Cyrus; Hanson, Mark A; Ozanne, Susan E; Green, Lucy R

    2013-10-01

    Suboptimal maternal nutrition and body composition are implicated in metabolic disease risk in adult offspring. We hypothesized that modest disruption of glucose homeostasis previously observed in young adult sheep offspring from ewes of a lower body condition score (BCS) would deteriorate with age, due to changes in skeletal muscle structure and insulin signaling mechanisms. Ewes were fed to achieve a lower (LBCS, n = 10) or higher (HBCS, n = 14) BCS before and during pregnancy. Baseline plasma glucose, glucose tolerance and basal glucose uptake into isolated muscle strips were similar in male offspring at 210 ± 4 weeks. Vastus total myofiber density (HBCS, 343 ± 15; LBCS, 294 ± 14 fibers/mm(2), P < .05) and fast myofiber density (HBCS, 226 ± 10; LBCS 194 ± 10 fibers/mm(2), P < .05), capillary to myofiber ratio (HBCS, 1.5 ± 0.1; LBCS 1.2 ± 0.1 capillary:myofiber, P < .05) were lower in LBCS offspring. Vastus protein levels of Akt1 were lower (83% ± 7% of HBCS, P < .05), and total glucose transporter 4 was increased (157% ± 6% of HBCS, P < .001) in LBCS offspring, Despite the reduction in total myofiber density in LBCS offspring, glucose tolerance was normal in mature adult life. However, such adaptations may lead to complications in metabolic control in an overabundant postnatal nutrient environment.

  8. Functional characterization of mammalian Wntless homolog in mammalian system.

    PubMed

    Wang, Li-Ting; Wang, Shih-Jong; Hsu, Shih-Hsien

    2012-07-01

    Wntless (GPR177) protein is a newly identified regulator of Wnt signals in Drosophila, but its cellular function in mammals is still unclear. In this study, we explored the expression pattern and potential cellular function of Wntless in mammalian cells. Wntless mRNA was expressed in many mouse tissues, including the spleen, lung, kidney, thymus, and stomach, and lower levels of expression were detected in the mouse brain and testis. Expression of Wntless protein analyzed by Western blot and immunohistochemical staining was only detected in the submucosa, muscle, ganglia, and nerve cells of murine large intestines. Both immunofluorescence staining and subcellular fraction extraction analysis revealed that endogenous Wntless protein was expressed predominantly in the cytoplasmic organelles with a morphologically dot-shaped distribution. Furthermore, overexpression of Wntless could be corrected by and may activate the nuclear factor-κB (NF-κB) signaling pathway in cancer (HeLa) cells. These results suggest that Wntless plays a role in signaling regulation during the formation of cancer in addition to its role as a retromer protein in mammalian systems.

  9. Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring.

    PubMed

    Pileggi, C A; Segovia, S A; Markworth, J F; Gray, C; Zhang, X D; Milan, A M; Mitchell, C J; Barnett, M P G; Roy, N C; Vickers, M H; Reynolds, C M; Cameron-Smith, D

    2016-03-01

    A high-saturated-fat diet (HFD) during pregnancy and lactation leads to metabolic disorders in offspring concomitant with increased adiposity and a proinflammatory phenotype in later life. During the fetal period, the impact of maternal diet on skeletal muscle development is poorly described, despite this tissue exerting a major influence on life-long metabolic health. This study investigated the effect of a maternal HFD on skeletal muscle anabolic, catabolic, and inflammatory signaling in adult rat offspring. Furthermore, the actions of maternal-supplemented conjugated linoleic acid (CLA) on these measures of muscle phenotype were investigated. A purified control diet (CD; 10% kcal fat), a CD supplemented with CLA (CLA; 10% kcal fat, 1% total fat as CLA), a high-fat (HFD; 45% kcal fat from lard), or a HFD supplemented with CLA (HFCLA; 45% kcal fat from lard, 1% total fat as CLA) was fed ad libitum to female Sprague-Dawley rats for 10 days before mating and throughout gestation and lactation. Male offspring received a standard chow diet from weaning, and the gastrocnemius was collected for analysis at day 150. Offspring from HF and HFCLA mothers displayed lower muscular protein content accompanied by elevated monocyte chemotactic protein-1, IL-6, and IL-1β concentrations. Phosphorylation of NF-κBp65 (Ser(536)) and expression of the catabolic E3 ligase muscle ring finger 1 (MuRF1) were increased in HF offspring, an effect reversed by maternal CLA supplementation. The present study demonstrates the importance of early life interventions to ameliorate the negative effects of poor maternal diet on offspring skeletal muscle development.

  10. The cholesterol-lowering agent methyl-β-cyclodextrin promotes glucose uptake via GLUT4 in adult muscle fibers and reduces insulin resistance in obese mice.

    PubMed

    Llanos, Paola; Contreras-Ferrat, Ariel; Georgiev, Tihomir; Osorio-Fuentealba, Cesar; Espinosa, Alejandra; Hidalgo, Jorge; Hidalgo, Cecilia; Jaimovich, Enrique

    2015-02-15

    Insulin stimulates glucose uptake in adult skeletal muscle by promoting the translocation of GLUT4 glucose transporters to the transverse tubule (T-tubule) membranes, which have particularly high cholesterol levels. We investigated whether T-tubule cholesterol content affects insulin-induced glucose transport. Feeding mice a high-fat diet (HFD) for 8 wk increased by 30% the T-tubule cholesterol content of triad-enriched vesicular fractions from muscle tissue compared with triads from control mice. Additionally, isolated muscle fibers (flexor digitorum brevis) from HFD-fed mice showed a 40% decrease in insulin-stimulated glucose uptake rates compared with fibers from control mice. In HFD-fed mice, four subcutaneous injections of MβCD, an agent reported to extract membrane cholesterol, improved their defective glucose tolerance test and normalized their high fasting glucose levels. The preincubation of isolated muscle fibers with relatively low concentrations of MβCD increased both basal and insulin-induced glucose uptake in fibers from controls or HFD-fed mice and decreased Akt phosphorylation without altering AMPK-mediated signaling. In fibers from HFD-fed mice, MβCD improved insulin sensitivity even after Akt or CaMK II inhibition and increased membrane GLUT4 content. Indinavir, a GLUT4 antagonist, prevented the stimulatory effects of MβCD on glucose uptake. Addition of MβCD elicited ryanodine receptor-mediated calcium signals in isolated fibers, which were essential for glucose uptake. Our findings suggest that T-tubule cholesterol content exerts a critical regulatory role on insulin-stimulated GLUT4 translocation and glucose transport and that partial cholesterol removal from muscle fibers may represent a useful strategy to counteract insulin resistance.

  11. Immediate effects of forearm elastic and nonelastic taping on wrist flexor muscle and grip strength of normal adults

    PubMed Central

    Cha, Hyun-Gyu; Kim, Myoung-Kwon; Shin, Young-Jun

    2016-01-01

    [Purpose] The purpose of this study was to examine the effects of forearm elastic taping on grip and wrist flexor muscle strength. [Subjects and Methods] This was a single-blind, crossover study. This study selected 40 healthy subjects with no history of orthopedic disorders and was conducted after consent to participate was obtained. Grip and wrist flexor muscle strength of subjects were assessed by a handheld dynamometer and a Commander Muscle Tester, respectively, with forearm elastic taping or nonelastic taping. [Results] After application of forearm elastic taping, grip strength and wrist flexor muscle strength significantly increased compared with the nonelastic taping group. [Conclusion] Application of forearm elastic taping is considered to have positive effects on improving wrist and grip strength. PMID:27821932

  12. Immunofluorescent localization of intermediate filaments (IFs) in helminths using anti-mammalian IFs monoclonal antibody.

    PubMed

    Sato, H; Kamiya, H

    2000-08-01

    Intermediate filaments (IFs) make up the cytoskeleton of most eukaryotic cells. In vertebrates, a number of IF proteins have been identified, showing distributions unique to tissue or cell type. Information on helminth IFs is limited to some nematode species. To observe immunofluorescent localization of IFs in helminth tissues, we selected a murine hybridoma clone producing IgM antibody to multiple types of mammalian IF proteins and examined cross-reactivity to helminth proteins. The selected monoclonal antibody (HUSM-9) cross-reacted well with IFs from nematode species such as Toxocara canis, Dirofilaria immitis, Anisakis simplex, and Trichinella britovi; strong immunofluorescence on cryostat sections was detected in the hypodermis, cords, body muscle, smooth muscle of the uterus, and other epithelial structures. In platyhelminths, i.e., adult Schistosoma mansoni, larval Taenia taeniaeformis, adult Taenia crassiceps, and Echinococcus multilocularis protoscolex, the reactivity was weaker than in nematodes, and localized in the body wall muscle and subtegumental tissue. Western blotting of 8 M urea extracts of parasites with the antibody detected a pair of clear bands in nematodes but not in S. mansoni or the cestodes. These results might be explained by sparse distribution of IFs in platyhelminths, or low affinity of the used antibody to platyhelminth IF proteins, or both.

  13. Myomaker is essential for muscle regeneration.

    PubMed

    Millay, Douglas P; Sutherland, Lillian B; Bassel-Duby, Rhonda; Olson, Eric N

    2014-08-01

    Regeneration of injured adult skeletal muscle involves fusion of activated satellite cells to form new myofibers. Myomaker is a muscle-specific membrane protein required for fusion of embryonic myoblasts, but its potential involvement in adult muscle regeneration has not been explored. We show that myogenic basic helix-loop-helix (bHLH) transcription factors induce myomaker expression in satellite cells during acute and chronic muscle regeneration. Moreover, genetic deletion of myomaker in adult satellite cells completely abolishes muscle regeneration, resulting in severe muscle destruction after injury. Myomaker is the only muscle-specific protein known to be absolutely essential for fusion of embryonic and adult myoblasts.

  14. Myomaker is essential for muscle regeneration

    PubMed Central

    Millay, Douglas P.; Sutherland, Lillian B.; Bassel-Duby, Rhonda

    2014-01-01

    Regeneration of injured adult skeletal muscle involves fusion of activated satellite cells to form new myofibers. Myomaker is a muscle-specific membrane protein required for fusion of embryonic myoblasts, but its potential involvement in adult muscle regeneration has not been explored. We show that myogenic basic helix–loop–helix (bHLH) transcription factors induce myomaker expression in satellite cells during acute and chronic muscle regeneration. Moreover, genetic deletion of myomaker in adult satellite cells completely abolishes muscle regeneration, resulting in severe muscle destruction after injury. Myomaker is the only muscle-specific protein known to be absolutely essential for fusion of embryonic and adult myoblasts. PMID:25085416

  15. Acute ascorbic acid ingestion increases skeletal muscle blood flow and oxygen consumption via local vasodilation during graded handgrip exercise in older adults.

    PubMed

    Richards, Jennifer C; Crecelius, Anne R; Larson, Dennis G; Dinenno, Frank A

    2015-07-15

    Human aging is associated with reduced skeletal muscle perfusion during exercise, which may be a result of impaired endothelium-dependent dilation and/or attenuated ability to blunt sympathetically mediated vasoconstriction. Intra-arterial infusion of ascorbic acid (AA) increases nitric oxide-mediated vasodilation and forearm blood flow (FBF) during handgrip exercise in older adults, yet it remains unknown whether an acute oral dose can similarly improve FBF or enhance the ability to blunt sympathetic vasoconstriction during exercise. We hypothesized that 1) acute oral AA would improve FBF (Doppler ultrasound) and oxygen consumption (V̇o2) via local vasodilation during graded rhythmic handgrip exercise in older adults (protocol 1), and 2) AA ingestion would not enhance sympatholysis in older adults during handgrip exercise (protocol 2). In protocol 1 (n = 8; 65 ± 3 yr), AA did not influence FBF or V̇o2 during rest or 5% maximal voluntary contraction (MVC) exercise, but increased FBF (199 ± 13 vs. 248 ± 16 ml/min and 343 ± 24 vs. 403 ± 33 ml/min; P < 0.05) and V̇o2 (26 ± 2 vs. 34 ± 3 ml/min and 43 ± 4 vs. 50 ± 5 ml/min; P < 0.05) at both 15 and 25% MVC, respectively. The increased FBF was due to elevations in forearm vascular conductance (FVC). In protocol 2 (n = 10; 63 ± 2 yr), following AA, FBF was similarly elevated during 15% MVC (∼ 20%); however, vasoconstriction to reflex increases in sympathetic activity during -40 mmHg lower-body negative pressure at rest (ΔFVC: -16 ± 3 vs. -16 ± 2%) or during 15% MVC (ΔFVC: -12 ± 2 vs. -11 ± 4%) was unchanged. Our collective results indicate that acute oral ingestion of AA improves muscle blood flow and V̇o2 during exercise in older adults via local vasodilation.

  16. Exercise and amino acid anabolic cell signaling and the regulation of skeletal muscle mass.

    PubMed

    Pasiakos, Stefan M

    2012-07-01

    A series of complex intracellular networks influence the regulation of skeletal muscle protein turnover. In recent years, studies have examined how cellular regulators of muscle protein turnover modulate metabolic mechanisms contributing to the loss, gain, or conservation of skeletal muscle mass. Exercise and amino acids both stimulate anabolic signaling potentially through several intracellular pathways including the mammalian target of rapamycin complex 1 and the mitogen activated protein kinase cell signaling cascades. As novel molecular regulators of muscle integrity continue to be explored, a contemporary analysis of the literature is required to understand the metabolic mechanisms by which contractile forces and amino acids affect cellular process that contribute to long-term adaptations and preservation of muscle mass. This article reviews the literature related to how exercise and amino acid availability affect cellular regulators of skeletal muscle mass, especially highlighting recent investigations that have identified mechanisms by which contractile forces and amino acids modulate muscle health. Furthermore, this review will explore integrated exercise and nutrition strategies that promote the maintenance of muscle health by optimizing exercise, and amino acid-induced cell signaling in aging adults susceptible to muscle loss.

  17. JunB transcription factor maintains skeletal muscle mass and promotes hypertrophy

    PubMed Central

    Raffaello, Anna; Milan, Giulia; Masiero, Eva; Carnio, Silvia; Lee, Donghoon

    2010-01-01

    The size of skeletal muscle cells is precisely regulated by intracellular signaling networks that determine the balance between overall rates of protein synthesis and degradation. Myofiber growth and protein synthesis are stimulated by the IGF-1/Akt/mammalian target of rapamycin (mTOR) pathway. In this study, we show that the transcription factor JunB is also a major determinant of whether adult muscles grow or atrophy. We found that in atrophying myotubes, JunB is excluded from the nucleus and that decreasing JunB expression by RNA interference in adult muscles causes atrophy. Furthermore, JunB overexpression induces hypertrophy without affecting satellite cell proliferation and stimulated protein synthesis independently of the Akt/mTOR pathway. When JunB is transfected into denervated muscles, fiber atrophy is prevented. JunB blocks FoxO3 binding to atrogin-1 and MuRF-1 promoters and thus reduces protein breakdown. Therefore, JunB is important not only in dividing populations but also in adult muscle, where it is required for the maintenance of muscle size and can induce rapid hypertrophy and block atrophy. PMID:20921137

  18. EMG activity of finger flexor muscles and grip force following low-dose transcutaneous electrical nerve stimulation in healthy adult subjects.

    PubMed

    Kafri, Michal; Zaltsberg, Nir; Dickstein, Ruth

    2015-01-01

    Somatosensory stimulation modulates cortical and corticospinal excitability and consequently affects motor output. Therefore, low-amplitude transcutaneous electrical nerve stimulation (TENS) has the potential to elicit favorable motor responses. The purpose of the two presented pilot studies was to shed light on TENS parameters that are relevant for the enhancement of two desirable motor outcomes, namely, electromyographic (EMG) activity and contraction strength of the finger flexors and wrist muscles. In 5 and 10 healthy young adults (in Study I and Study II, respectively) TENS was delivered to the volar aspect of the forearm. We manipulated TENS frequency (150 Hz vs. 5 Hz), length of application (10, 20, and 60 min), and side of application (unilateral, right forearm vs. bilateral forearms). EMG amplitude and grip force were measured before (Pre), immediately after (Post), and following 15 min of no stimulation (Study I only). The results indicated that low-frequency bursts of TENS applied to the skin overlying the finger flexor muscles enhance the EMG activity of the finger flexors and grip force. The increase in EMG activity of the flexor muscles was observed after 20 min of stimulation, while grip force was increased only after 1 h. The effects of uni- and bilateral TENS were comparable. These observations allude to a modulatory effect of TENS on the tested motor responses; however, unequivocal conclusions of the findings are hampered by individual differences that affect motor outcomes, such as in level of attention.

  19. Myogenic progenitors and imaging single-cell flow analysis: a model to study commitment of adult muscle stem cells.

    PubMed

    Trapecar, Martin; Kelc, Robi; Gradisnik, Lidija; Vogrin, Matjaz; Rupnik, Marjan Slak

    2014-12-01

    Research on skeletal muscles suffers from a lack of appropriate human models to study muscle formation and regeneration on the regulatory level of single cells. This hampers both basic understanding and the development of new therapeutic approaches. The use of imaging multicolour flow cytometry and myogenic stem cells can help fill this void by allowing researchers to visualize and quantify the reaction of individual cultured cells to bioactives or other physiological impulses. As proof of concept, we subjected human CD56+ satellite cells to reference bioactives follistatin and Malva sylvestris extracts and then used imaging multicolor flow cytometry to visualize the stepwise activation of myogenic factors MyoD and myogenin in individual cells. This approach enabled us to evaluate the potency of these bioactives to stimulate muscle commitment. To validate this method, we used multi-photon confocal microscopy to confirm the potential of bioactives to stimulate muscle differentiation and expression of desmin. Imaging multicolor flow cytometry revealed statistically significant differences between treated and untreated groups of myogenic progenitors and we propose the utilization of this concept as an integral part of future muscle research strategies.

  20. Effects of free leucine supplementation and resistance training on muscle strength and functional status in older adults: a randomized controlled trial

    PubMed Central

    Trabal, Joan; Forga, Maria; Leyes, Pere; Torres, Ferran; Rubio, Jordi; Prieto, Esther; Farran-Codina, Andreu

    2015-01-01

    Objective To assess the effect of free leucine supplementation combined with resistance training versus resistance training only on muscle strength and functional status in older adults. Methods This was a randomized, double-blind, placebo-controlled, parallel study with two intervention groups. Thirty older adults were randomly assigned to receive either 10 g leucine/day (leucine group [LG], n=15) or a placebo (control group [CG], n=15), plus resistance training over a 12-week period. Maximal overcoming isometric leg strength, functional status, nutritional status, body composition, health-related quality of life, depression, and dietary intake were assessed at 4 and 12 weeks. Missing data at 12 weeks were handled using mixed models for repeated measurements for data imputation. Results Twenty-four subjects completed the 4-week assessment and eleven completed the 12-week intervention. Clinically significant gains were found in isometric leg strength at both assessment time points. Analysis of the effect size also showed how participants in LG outperformed those in CG for chair stands and the timed up and go test. No significant changes were observed for the rest of the outcomes. Conclusion Our combined analysis showed moderate changes in isometric leg muscle strength and certain components of functional status. The magnitude of changes found on these outcomes should be qualified as a positive effect of the concomitant intervention. PMID:25926725

  1. Proteasome dysfunction induces muscle growth defects and protein aggregation

    PubMed Central

    Kitajima, Yasuo; Tashiro, Yoshitaka; Suzuki, Naoki; Warita, Hitoshi; Kato, Masaaki; Tateyama, Maki; Ando, Risa; Izumi, Rumiko; Yamazaki, Maya; Abe, Manabu; Sakimura, Kenji; Ito, Hidefumi; Urushitani, Makoto; Nagatomi, Ryoichi; Takahashi, Ryosuke; Aoki, Masashi

    2014-01-01

    ABSTRACT The ubiquitin–proteasome and autophagy–lysosome pathways are the two major routes of protein and organelle clearance. The role of the proteasome pathway in mammalian muscle has not been examined in vivo. In this study, we report that the muscle-specific deletion of a crucial proteasomal gene, Rpt3 (also known as Psmc4), resulted in profound muscle growth defects and a decrease in force production in mice. Specifically, developing muscles in conditional Rpt3-knockout animals showed dysregulated proteasomal activity. The autophagy pathway was upregulated, but the process of autophagosome formation was impaired. A microscopic analysis revealed the accumulation of basophilic inclusions and disorganization of the sarcomeres in young adult mice. Our results suggest that appropriate proteasomal activity is important for muscle growth and for maintaining myofiber integrity in collaboration with autophagy pathways. The deletion of a component of the proteasome complex contributed to myofiber degeneration and weakness in muscle disorders that are characterized by the accumulation of abnormal inclusions. PMID:25380823

  2. Crustacean muscle plasticity: molecular mechanisms determining mass and contractile properties.

    PubMed

    Mykles, D L

    1997-07-01

    Two crustacean models for understanding molecular mechanisms of muscle plasticity are reviewed. Metabolic changes underlying muscle protein synthesis and degradation have been examined in the Bermuda land crab, Gecarcinus lateralis. During proecdysis, the claw closer muscle undergoes a programmed atrophy, which results from a highly controlled breakdown of myofibrillar proteins by Ca(2+)-dependent and, possibly, ATP/ubiquitin-dependent proteolytic enzymes. The advantage of this model is that there is neither fiber degeneration nor contractile-type switching, which often occurs in mammalian skeletal muscles. The second model uses American lobster, Homarus americanus, to understand the genetic regulation of fiber-type switching. Fibers in the claw closer muscles undergo a developmentally-regulated transformation as the isomorphic claws of larvae and juveniles differentiate into the heteromorphic cutter and crusher claws of adults. This switching occurs at the boundary between fast- and slow-fiber regions, and thus the transformation of a specific fiber is determined by its position within the muscle. The ability to predict fiber switching can be exploited to isolate and identify putative master regulatory factors that initiate and coordinate the expression of contractile proteins.

  3. Decreased lower limb muscle recruitment contributes to the inability of older adults to recover with a single step following a forward loss of balance.

    PubMed

    Cronin, Neil J; Barrett, Rod S; Lichtwark, Glen; Mills, Peter M; Carty, Christopher P

    2013-10-01

    In response to a balance disturbance, older individuals often require multiple steps to prevent a fall. Reliance on multiple steps to recover balance is predictive of a future fall, so studies should determine the mechanisms underlying differences between older adults who can and cannot recover balance with a single step. This study compared neural activation parameters of the major leg muscles during balance recovery from a sudden forward loss of balance in older individuals capable of recovering with a single step and those who required multiple steps to regain balance. Eighty-one healthy, community dwelling adults aged 70±3 participated. Loss of balance was induced by releasing participants from a static forward lean. Participants performed four trials at three initial lean magnitudes and were subsequently classified as single or multiple steppers. Although step length was shorter in multiple compared to single steppers (F=9.64; p=0.02), no significant differences were found between groups in EMG onset time in the step limb muscles (F=0.033-0.769; p=0.478-0.967). However, peak EMG normalised to values obtained during maximal voluntary contraction was significantly higher in single steppers in 6 of the 7 stepping limb muscles (F=1.054-4.167; p=0.045-0.024). These data suggest that compared to multiple steppers, single steppers recruit a larger proportion of the available motor unit pool during balance recovery. Thus, modulation of EMG amplitude plays a larger role in balance recovery than EMG timing in this context.

  4. Effects of priming exercise on the speed of adjustment of muscle oxidative metabolism at the onset of moderate-intensity step transitions in older adults.

    PubMed

    De Roia, Gabriela; Pogliaghi, Silvia; Adami, Alessandra; Papadopoulou, Christina; Capelli, Carlo

    2012-05-15

    Aging is associated with a functional decline of the oxidative metabolism due to progressive limitations of both O(2) delivery and utilization. Priming exercise (PE) increases the speed of adjustment of oxidative metabolism during successive moderate-intensity transitions. We tested the hypothesis that such improvement is due to a better matching of O(2) delivery to utilization within the working muscles. In 21 healthy older adults (65.7 ± 5 yr), we measured contemporaneously noninvasive indexes of the overall speed of adjustment of the oxidative metabolism (i.e., pulmonary Vo(2) kinetics), of the bulk O(2) delivery (i.e., cardiac output), and of the rate of muscle deoxygenation (i.e., deoxygenated hemoglobin, HHb) during moderate-intensity step transitions, either with (ModB) or without (ModA) prior PE. The local matching of O(2) delivery to utilization was evaluated by the ΔHHb/ΔVo(2) ratio index. The overall speed of adjustment of the Vo(2) kinetics was significantly increased in ModB compared with ModA (P < 0.05). On the contrary, the kinetics of cardiac output was unaffected by PE. At the muscle level, ModB was associated with a significant reduction of the "overshoot" in the ΔHHb/ΔVo(2) ratio compared with ModA (P < 0.05), suggesting an improved O(2) delivery. Our data are compatible with the hypothesis that, in older adults, PE, prior to moderate-intensity exercise, beneficially affects the speed of adjustment of oxidative metabolism due to an acute improvement of the local matching of O(2) delivery to utilization.

  5. Effects of Neuromuscular Electrical Stimulation on the Masticatory Muscles and Physiologic Sleep Variables in Adults with Cerebral Palsy: A Novel Therapeutic Approach

    PubMed Central

    Giannasi, Lilian Chrystiane; Matsui, Miriam Yumi; Freitas, Sandra Regina Batista; Caldas, Bruna F.; Grossmann, Eduardo; Amorim, José Benedito O.; dos Santos, Israel dos Reis; Oliveira, Luis Vicente Franco; Oliveira, Claudia Santos; Gomes, Monica Fernandes

    2015-01-01

    Cerebral palsy (CP) is a term employed to define a group of non-progressive neuromotor disorders caused by damage to the immature or developing brain, with consequent limitations regarding movement and posture. CP may impair orapharygeal muscle tone, leading to a compromised chewing function and to sleep disorders (such as obstructive sleep apnea). Thirteen adults with CP underwent bilateral masseter and temporalis neuromuscular electrical stimulation (NMES) therapy. The effects on the masticatory muscles and sleep variables were evaluated using electromyography (EMG) and polysomnography (PSG), respectively, prior and after 2 months of NMES. EMG consisted of 3 tests in different positions: rest, mouth opening and maximum clenching effort (MCE). EMG values in the rest position were 100% higher than values recorded prior to therapy for all muscles analyzed (p < 0.05); mean mouth opening increased from 38.0 ± 8.0 to 44.0 ± 10.0 cm (p = 0.03). A significant difference in MCE was found only for the right masseter. PSG revealed an improved in the AHI from 7.2±7.0/h to 2.3±1.5/h (p < 0.05); total sleep time improved from 185 min to 250 min (p = 0.04) and minimun SaO2 improved from 83.6 ± 3.0 to 86.4 ± 4.0 (p = 0.04). NMES performed over a two-month period led to improvements in the electrical activity of the masticatory muscles at rest, mouth opening, isometric contraction and sleep variables, including the elimination of obstructive sleep apnea events in patients with CP. Trial Registration ReBEC RBR994XFS http://www.ensaiosclinicos.gov.br PMID:26247208

  6. Your Muscles

    MedlinePlus

    ... Room? What Happens in the Operating Room? Your Muscles KidsHealth > For Kids > Your Muscles A A A ... and skeletal (say: SKEL-uh-tul) muscle. Smooth Muscles Smooth muscles — sometimes also called involuntary muscles — are ...

  7. Adjustments of pulmonary O2 uptake and muscle deoxygenation during ramp incremental exercise and constant-load moderate-intensity exercise in young and older adults

    PubMed Central

    Gravelle, Braden M. R.; Murias, Juan M.; Spencer, Matthew D.; Paterson, Donald H.

    2012-01-01

    The matching of muscle O2 delivery to O2 utilization can be inferred from the adjustments in muscle deoxygenation (Δ[HHb]) and pulmonary O2 uptake (V̇o2p). This study examined the adjustments of V̇o2p and Δ[HHb] during ramp incremental (RI) and constant-load (CL) exercise in adult males. Ten young adults (YA; age: 25 ± 5 yr) and nine older adults (OA; age: 70 ± 3 yr) completed two RI tests and six CL step transitions to a work rate (WR) corresponding to 1) 80% of the estimated lactate threshold (same relative WR) and 2) 50 W (same absolute WR). V̇o2p was measured breath by breath, and Δ[HHb] of the vastus lateralis was measured using near-infrared spectroscopy. Δ[HHb]-WR profiles were normalized from baseline (0%) to peak Δ[HHb] (100%) and fit using a sigmoid function. The sigmoid slope (d) was greater (P < 0.05) in OA (0.027 ± 0.01%/W) compared with YA (0.017 ± 0.01%/W), and the c/d value (a value corresponding to 50% of the amplitude) was smaller (P < 0.05) for OA (133 ± 40 W) than for YA (195 ± 51 W). No age-related differences in the sigmoid parameters were reported when WR was expressed as a percentage of peak WR. V̇o2p kinetics compared with Δ[HHb] kinetics for the 50-W transition were similar between YA and OA; however, Δ[HHb] kinetics during the transition to 80% of the lactate threshold were faster than V̇o2p kinetics in both groups. The greater reliance on O2 extraction displayed in OA during RI exercise suggests a lower O2 delivery-to-O2 utilization relationship at a given absolute WR compared with YA. PMID:22961268

  8. Cochrane review: Whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults.

    PubMed

    Costello, Joseph T; Baker, Philip Ra; Minett, Geoffrey M; Bieuzen, Francois; Stewart, Ian B; Bleakley, Chris

    2016-01-14

    Delayed-onset muscle soreness, or 'DOMS', affects many people after exercise and can impair future performance. It usually peaks one to four days after exercise and several strategies are used to overcome it. The effectiveness and safety of many of these strategies applied and promoted is unknown. This article is protected by copyright. All rights reserved.

  9. Three Hierarchies in Skeletal Muscle Fibre Classification Allotype, Isotype and Phenotype

    NASA Technical Reports Server (NTRS)

    Hoh, Joseph F. Y.; Hughes, Suzanne; Hugh, Gregory; Pozgaj, Irene

    1991-01-01

    Immunocytochemical analyses using specific anti-myosin antibodies of mammalian muscle fibers during regeneration, development, and after denervation have revealed two distinct myogenic components determining fiber phenotype. The jaw-closing muscles of the cat contain superfast fibers which express a unique myosin not found in limb muscles. When superfast muscle is transplanted into a limb muscle bed, regenerating myotubes synthesize superfast myosin independent of innervation. Reinnervation by the nerve to a fast muscle leads to the expression of superfast and not fast myosin, while reinnervation by the nerve to a slow muscle leads to the expression of a slow myosin. When limb muscle is transplanted into the jaw muscle bed, only limb myosins are synthesized. Thus jaw and limb muscles belong to distinct allotypes, each with a unique range of phenotype options, the expressions of which may be modulated by the nerve. Primary and secondary myotubes in developing jaw and limb muscles are observed to belong to different categories characterized by different patterns of myosin gene expression. By taking into consideration the pattern of myosins synthesized and the changes in fiber size after denervation, 3 types of primary (fast, slow, and intermediate) fibers can be distinguished in rat fast limb muscles. All primaries synthesize slow myosin soon after their formation, but this is withdrawn in fast and intermediate primaries at different times. After neonatal denervation, slow and intermediate primaries express slow primaries hypertrophy with other fibers atrophy. In the mature rat, the number of slow fibers in the EDL is less than the number of slow primaries. Upon denervation, hypertrophic slow fibers matching the number and topographic distribution of slow primaries appear, suggesting that a subpopulation of the slow primaries acquire the fast phenotype during adult life, but reveal their original identity as slow primaries in response to denervation by hypertrophying

  10. Effect of flywheel-based resistance exercise on processes contributing to muscle atrophy during unloading in adult rats.

    PubMed

    Dupont-Versteegden, Esther E; Fluckey, James D; Knox, Micheal; Gaddy, Dana; Peterson, Charlotte A

    2006-07-01

    Flywheel-based resistance exercise (RE) attenuates muscle atrophy during hindlimb suspension. We have previously shown that protein synthesis is elevated in response to RE, but the effect on protein degradation, cell proliferation, or apoptosis was not investigated. We hypothesized that, in addition to affecting protein synthesis, RE inhibits processes that actively contribute to muscle atrophy during hindlimb suspension. Male rats were housed in regular cages (control), tail suspended for 2 wk (HS), or HS with RE every other day for 2 wk (HSRE). Although RE attenuated soleus muscle atrophy during HS, the observed fivefold elevation in apoptosis and the 53% decrease in cell proliferation observed with HS were unaffected by RE. Expression of genes encoding components of the ubiquitin-proteasome pathway of protein degradation were elevated with HS, including ubiquitin, MAFbx, Murf-1, Nedd4, and XIAP, and proteasome subunits C2 and C9. Total ubiquitinated protein was increased with HS, but proteasome activity was not different from control. RE selectively altered the expression of different components of this pathway: MAFbx, Murf-1, and ubiquitin mRNA abundance were downregulated, whereas C2 and C9 subunits remained elevated. Similarly, Nedd4 and XIAP continued to be upregulated, potentially accounting for the observed augmentation in total ubiquitinated protein with RE. Thus a different constellation of proteins is likely ubiquitinated with RE due to altered ubiquitin ligase composition. In summary, the flywheel-based resistance exercise paradigm used in this study is associated with the inhibition of some mechanisms associated with muscle atrophy, such as the increase in MAFbx and Murf-1, but not with others, such as proteasome subunit remodeling, apoptosis, and decreased proliferation, potentially accounting for the inability to completely restore muscle mass. Identifying specific exercise parameters that affect these latter processes may be useful in designing

  11. The effects of water temperature on the energetic costs of juvenile and adult California sea lions (Zalophus californianus): the importance of skeletal muscle thermogenesis for thermal balance.

    PubMed

    Liwanag, H E M; Williams, T M; Costa, D P; Kanatous, S B; Davis, R W; Boyd, I L

    2009-12-01

    As highly mobile marine predators, many pinniped species routinely encounter a wide range of water temperatures during foraging and in association with seasonal, geographical and climatic changes. To determine how such variation in environmental temperature may impact energetic costs in otariids, we determined the thermal neutral zone of adult and juvenile California sea lions (Zalophus californianus) by measuring resting metabolic rate using open-flow respirometry. Five adult female (body mass range =82.2-107.2 kg) and four juvenile (body mass=26.2-36.5 kg) sea lions were examined over experimental water temperatures ranging from 0 to 20 degrees C (adults) or 5 to 20 degrees C (juveniles). The metabolic rate of adult sea lions averaged 6.4+/-0.64 ml O(2) kg(-1) min(-1) when resting within the thermal neutral zone. The lower critical temperature of adults was 6.4+/-2.2 degrees C, approximately 4 degrees C lower than sea surface temperatures routinely encountered off coastal California. In comparison, juvenile sea lions did not demonstrate thermal neutrality within the range of water temperatures examined. Resting metabolic rate of the younger animals, 6.3+/-0.53 ml O(2) kg(-1) min(-1), increased as water temperature approached 12 degrees C, and suggested a potential thermal limitation in the wild. To determine whether muscle thermogenesis during activity could mitigate this limitation, we measured the active metabolic rate of juveniles swimming at water temperature (T(water))=5, 12 and 20 degrees C. No significant difference (F=0.377, P=0.583) in swimming metabolic rate was found among water temperatures, suggesting that thermal disadvantages due to small body size in juvenile sea lions may be circumvented by recycling endogenous heat during locomotor activity.

  12. Circadian Rhythms, the Molecular Clock, and Skeletal Muscle

    PubMed Central

    Lefta, Mellani; Wolff, Gretchen; Esser, Karyn A.

    2015-01-01

    Almost all organisms ranging from single cell bacteria to humans exhibit a variety of behavioral, physiological, and biochemical rhythms. In mammals, circadian rhythms control the timing of many physiological processes over a 24-h period, including sleep-wake cycles, body temperature, feeding, and hormone production. This body of research has led to defined characteristics of circadian rhythms based on period length, phase, and amplitude. Underlying circadian behaviors is a molecular clock mechanism found in most, if not all, cell types including skeletal muscle. The mammalian molecular clock is a complex of multiple oscillating networks that are regulated through transcriptional mechanisms, timed protein turnover, and input from small molecules. At this time, very little is known about circadian aspects of skeletal muscle function/metabolism but some progress has been made on understanding the molecular clock in skeletal muscle. The goal of this chapter is to provide the basic terminology and concepts of circadian rhythms with a more detailed review of the current state of knowledge of the molecular clock, with reference to what is known in skeletal muscle. Research has demonstrated that the molecular clock is active in skeletal muscles and that the muscle-specific transcription factor, MyoD, is a direct target of the molecular clock. Skeletal muscle of clock-compromised mice, Bmal1−/− and ClockΔ19 mice, are weak and exhibit significant disruptions in expression of many genes required for adult muscle structure and metabolism. We suggest that the interaction between the molecular clock, MyoD, and metabolic factors, such as PGC-1, provide a potential system of feedback loops that may be critical for both maintenance and adaptation of skeletal muscle. PMID:21621073

  13. Circadian aspects of mammalian parturition: a review.

    PubMed

    Olcese, James

    2012-02-05

    The identification of circadian clocks in endocrine tissues has added considerable depth and complexity to our understanding of their physiology. A growing body of research reveals circadian clock gene expression in the uterus of non-pregnant and pregnant rodents. This review will focus on the mammalian uterus and its rhythmicity, particularly as it pertains to the circadian timing of parturition. This key event in the reproductive axis shows dramatic species-specific differences in its circadian phase. It is proposed here that these differences in the phasing of mammalian parturition are likely a function of opposite uterine cell responses to humoral cues. The argument will be made that melatonin fulfills many of the criteria to serve as a circadian signal in the initiation of human parturition, including specific actions on uterine smooth muscle cells that are consistent with a role for this hormone in the circadian timing of parturition.

  14. Intrafusal muscle fibre types in frog spindles.

    PubMed

    Diwan, F H; Ito, F

    1989-04-01

    Muscle spindles from bullfrog semitendinosus, iliofibularis and sartorius muscles were examined with light and electron microscopy. Four types of intrafusal muscle fibre were identified according to their diameter, central nucleation and reticular zone arrangement: a large nuclear bag fibre, a medium nuclear bag fibre, and two types of small nuclear chain fibres with and without a reticular zone, respectively. It is suggested that they are comparable to the nuclear bag1, bag2 and chain fibres in mammalian muscle spindles.

  15. Dual innervation of end-plate sites and its consequences for neuromuscular transmission in muscles of adult Xenopus laevis.

    PubMed Central

    Angaut-Petit, D; Mallart, A

    1979-01-01

    1. Electrophysiological study of dually innervated end-plate sites was carried out in Xenopus laevis pectoral muscle fibres. End-plate potentials (e.p.p.s) and miniature end-plate potentials (m.e.p.p.s) have been recorded in Mg-blocked preparations. 2. The mean quantal content (m) of each e.p.p. at dually innervated end-plates was significantly smaller than the corresponding values obtained at singly innervated ones. At a given doubly innervated end-plate site the values of m tended to be inversely related, so that the compound value of m (obtained by adding them) was in the same range as that found in singly innervated junctions. These findings were taken to suggest the existence of an upper limit in the average amount of transmitter released at a synaptic site. 3. It was found that neither intermittent presynaptic conduction block, nor particular muscle fibre properties could account for the low values of m in dual end plates. The small size of the nerve terminals appears to be the most likely explanation. 4. The sensitivity to acetylcholine and muscle fibre electrical properties were investigated; no differences were found between fibres with sub- or suprathreshold e.p.p.s. 5. The nature of the factors responsible for this presumed small size of the nerve endings (competition between nerve endings for a limited synaptic space on the muscle membrane or reciprocal interaction between closely located terminals) as well as the possible origins of polyinnervation are discussed. PMID:222897

  16. High-dose statin use does not impair aerobic capacity or skeletal muscle function in older adults

    PubMed Central

    Stock, Anthoney A.; Harman, S. Mitchell

    2008-01-01

    3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are lipid-lowering agents widely employed for atherosclerosis prevention. HMG-CoA reductase blockade reduces skeletal muscle coenzyme Q10 (CoQ10) levels and mitochondrial respiratory chain activities and may produce mild to severe skeletal muscle myopathy. This study investigated whether high-dose statin treatment would result in measurably decreased exercise capacity in older men and women. Maximal oxygen consumption, aerobic endurance, oxygen uptake kinetics, maximal strength, muscular power, and muscular endurance were measured before and after 12 weeks of statin treatment (simvastatin, 80 mg/day) in nine men and one woman, ages 55–76 years, with LDL-cholesterol levels >3.3 mmol/l (mean = 4.2 ± 0.2 mmol/l). Myalgia symptoms were assessed every 4 weeks. As expected, statin treatment resulted in significant decreases in LDL- and total-cholesterol levels (P < 0.01) with no significant changes in HDL-cholesterol or triglyceride levels. No significant changes were observed in aerobic capacity, endurance, oxygen kinetics or any measures of muscle function. No subject reported symptoms of myalgia, cramps, or weakness during the study. In the absence of myalgia or myopathic symptoms, high-dose simvastatin treatment did not impair exercise capacity in hyperlipidemic older individuals. We conclude that decreases in intramuscular CoQ10, in most patients on high dose statin treatment may not be clinically relevant, due to inter-individual variability in the degree of CoQ10 depletion, sensitivity of muscle to decreases in CoQ10, or both. PMID:19424852

  17. Sarcoplasmic reticulum Ca2+ depletion in adult skeletal muscle fibres measured with the biosensor D1ER.

    PubMed

    Jiménez-Moreno, Ramón; Wang, Zhong-Ming; Messi, María Laura; Delbono, Osvaldo

    2010-04-01

    The endoplasmic/sarcoplasmic reticulum (ER/SR) plays a crucial role in cytoplasmic signalling in a variety of cells. It is particularly relevant to skeletal muscle fibres, where this organelle constitutes the main Ca2+ store for essential functions, such as contraction. In this work, we expressed the cameleon biosensor D1ER by in vivo electroporation in the mouse flexor digitorum brevis (FDB) muscle to directly assess SR Ca2+ depletion in response to electrical and pharmacological stimulation. The main conclusions are: (1) D1ER is expressed in the SR of FDB fibres according to both di-8-(amino naphthyl ethenyl pyridinium) staining experiments and reductions in the Förster resonance energy transfer signal consequent to SR Ca2+ release; (2) the amplitude of D1ER citrine/cyan fluorescent protein (CFP) ratio evoked by either 4-chloro-m-cresol (4-CmC) or electrical stimulation is directly proportional to the basal citrine/CFP ratio, which indicates that SR Ca2+ modulates ryanodine-receptor-isoform-1-mediated SR Ca2+ release in the intact muscle fibre; (3) SR Ca2+ release, measured as D1ER citrine/CFP signal, is voltage-dependent and follows a Boltzmann function; and (4) average SR Ca2+ depletion is 20% in response to 4-CmC and 6.4% in response to prolonged sarcolemmal depolarization. These results indicate that significantly depleting SR Ca2+ content under physiological conditions is difficult.

  18. Surgical Treatment Guidelines for Digital Deformity Associated With Intrinsic Muscle Spasticity (Intrinsic Plus Foot) in Adults With Cerebral Palsy.

    PubMed

    Boffeli, Troy J; Collier, Rachel C

    2015-01-01

    Intrinsic plus foot deformity has primarily been associated with cerebral palsy and involves spastic contracture of the intrinsic musculature with resultant toe deformities. Digital deformity is caused by a dynamic imbalance between the intrinsic muscles in the foot and extrinsic muscles in the lower leg. Spastic contracture of the toes frequently involves curling under of the lesser digits or contracture of the hallux into valgus or plantarflexion deformity. Patients often present with associated pressure ulcers, deformed toenails, shoe or brace fitting challenges, and pain with ambulation or transfers. Four different patterns of intrinsic plus foot deformity have been observed by the authors that likely relate to the different patterns of muscle involvement. Case examples are provided of the 4 patterns of intrinsic plus foot deformity observed, including global intrinsic plus lesser toe deformity, isolated intrinsic plus lesser toe deformity, intrinsic plus hallux valgus deformity, and intrinsic plus hallux flexus deformity. These case examples are presented to demonstrate each type of deformity and our approach for surgical management according to the contracture pattern. The surgical approach has typically involved tenotomy, capsulotomy, or isolated joint fusion. The main goals of surgical treatment are to relieve pain and reduce pressure points through digital realignment in an effort to decrease the risk of pressure sores and allow more effective bracing to ultimately improve the patient's mobility.

  19. The effects of modified wall squat exercises on average adults' deep abdominal muscle thickness and lumbar stability.

    PubMed

    Cho, Misuk

    2013-06-01

    [Purpose] The purpose of this study was to compare the effects of bridge exercises applying the abdominal drawing-in method and modified wall squat exercises on deep abdominal muscle thickness and lumbar stability. [Subjects] A total of 30 subjects were equally divided into an experimental group and a control group. [Methods] The experimental group completed modified wall squat exercises, and the control group performed bridge exercises. Both did so for 30 minutes three times per week over a six-week period. Both groups' transversus abdominis (Tra), internal oblique (IO), and multifidus muscle thickness were measured using ultrasonography, while their static lumbar stability and dynamic lumbar stability were measured using a pressure biofeedback unit. [Results] A comparison of the pre-intervention and post-intervention measures of the experimental group and the control group was made; the Tra and IO thicknesses were significantly different in both groups. [Conclusion] The modified wall squat exercise and bridge exercise affected the thicknesses of the Tra and the IO muscles. While the bridge exercise requirs space and a mattress to lie on, the modified wall squat exercise can be conveniently performed anytime.

  20. 3-Methylhistidine in actin and other muscle proteins

    PubMed Central

    Johnson, P.; Harris, C. I.; Perry, S. V.

    1967-01-01

    1. By the use of the extended elution system for basic amino acid analysis, 3-methylhistidine has been detected in hydrolysates of actin isolated from mammalian, fish and bird skeletal muscle. 2. Evidence is presented to indicate that 3-methylhistidine forms part of the primary structure and that in rabbit actin this residue is restricted to one peptide fraction obtained from the tryptic digest. 3. Rabbit skeletal-muscle actin has a 3-methylhistidine:histidine ratio 1:7·6, indicating a minimum molecular weight of 47600. 4. Adult rabbit myosin contains approximately 2 3-methylhistidine residues/mol. These residues are localized in the heavy meromyosin part of the molecule, and are restricted to the major component obtained after succinylation. ImagesFig. 1.Fig. 2.Fig. 3. PMID:6056634

  1. Diethyl hexyl phthalate-induced changes in insulin signaling molecules and the protective role of antioxidant vitamins in gastrocnemius muscle of adult male rat.

    PubMed

    Srinivasan, Chinnapaiyan; Khan, Adam Ismail; Balaji, Venkataraman; Selvaraj, Jayaraman; Balasubramanian, Karundevi

    2011-12-01

    Diethyl hexyl phthalate (DEHP) is an endocrine disruptor, it influences various organ systems in human beings and experimental animals. DEHP reduced the serum testosterone and increased the blood glucose, estradiol, T(3) and T(4) in rats. However, the effect of DEHP on insulin signaling and glucose oxidation in skeletal muscle is not known. Adult male albino rats were divided into four groups: Group I: Control; Groups II and III: DEHP treated (dissolved in olive oil at a dose of 10 and 100mg/kg body weight, respectively, once daily through gastric intubation for 30 days); and Group IV: DEHP (100mg/kg body weight) plus vitamins E (50mg/kg body weight) and C (100mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubation for 30 days. On completion of treatment, animals were euthanized and perfused (whole body); gastrocnemius muscle was dissected out and subjected to assessment of various parameters. DEHP treatment increased the H(2)O(2), hydroxyl radical levels and lipid peroxidation which disrupt the membrane integrity and insulin receptor. DEHP impaired the insulin signal transduction, glucose uptake and oxidation through decreased expression of plasma membrane GLUT4, which may partly be responsible for the elevation of fasting blood glucose level. The present study suggests that DEHP exposure affects glucose oxidation in skeletal muscle and is mediated through enhanced lipid peroxidation, impaired insulin signaling and GLUT4 expression in plasma membrane. Antioxidant vitamins (C and E) have a protective role against the adverse effect of DEHP.

  2. Growth response and expression of muscle growth-related candidate genes in adult zebrafish fed plant and fishmeal protein-based diets.

    PubMed

    Ulloa, Pilar E; Peña, Andrea A; Lizama, Carla D; Araneda, Cristian; Iturra, Patricia; Neira, Roberto; Medrano, Juan F

    2013-03-01

    The main objective of this study was to examine the effects of a plant protein- vs. fishmeal-based diet on growth response in a population of 24 families, as well as expression of growth-related genes in the muscle of adult zebrafish (Danio rerio). Each family was split to create two fish populations with similar genetic backgrounds, and the fish were fed either fishmeal (FM diet) or plant protein (PP diet) as the unique protein source in their diets from 35 to 98 days postfertilization (dpf). To understand the effect of the PP diet on gene expression, individuals from three families, representative of the mean weight in both populations, were selected. To understand the effect of familiar variation on gene expression, the same families were evaluated separately. At 98 dpf, growth-related genes Igf1a, Igf2a, mTOR, Pld1a, Mrf4, Myod, Myogenin, and Myostatin1b were evaluated. In males, Myogenin, Mrf4, and Igf2a showed changes attributable to the PP diet. In females, the effect of the PP diet did not modulate the expression in any of the eight genes studied. The effect of familiar variation on gene expression was observed among families. This study shows that PP diet and family variation have effects on gene expression in fish muscle.

  3. The evolutionarily conserved RNA binding protein SMOOTH is essential for maintaining normal muscle function.

    PubMed

    Draper, Isabelle; Tabaka, Meg E; Jackson, F Rob; Salomon, Robert N; Kopin, Alan S

    2009-01-01

    The Drosophila smooth gene encodes an RNA binding protein that has been well conserved through evolution. To investigate the pleiotropic functions mediated by the smooth gene, we have selected and characterized two sm mutants, which are viable as adults yet display robust phenotypes (including a significant decrease in lifespan). Utilizing these mutants, we have made the novel observation that disruption of the smooth/CG9218 locus leads to age-dependent muscle degeneration, and motor dysfunction. Histological characterization of adult sm mutants revealed marked abnormalities in the major thoracic tubular muscle: the tergal depressor of the trochanter (TDT). Corresponding defects include extensive loss/disruption of striations and nuclei. These pathological changes are recapitulated in flies that express a smooth RNA interference construct (sm RNAi) in the mesoderm. In contrast, targeting sm RNAi constructs to motor neurons does not alter muscle morphology. In addition to examining the TDT phenotype, we explored whether other muscular abnormalities were evident. Utilizing physiological assays developed in the laboratory, we have found that the thoracic muscle defect is preceded by dysmotility of the gastrointestinal tract. SMOOTH thus joins a growing list of hnRNPs that have previously been linked to muscle physiology/pathophysiology. Our findings in Drosophila set the stage for investigating the role of the corresponding mammalian homolog, hnRNP L, in muscle function.

  4. Mammalian development in space

    NASA Technical Reports Server (NTRS)

    Ronca, April E.

    2003-01-01

    Life on Earth, and thus the reproductive and ontogenetic processes of all extant species and their ancestors, evolved under the constant influence of the Earth's l g gravitational field. These considerations raise important questions about the ability of mammals to reproduce and develop in space. In this chapter, I review the current state of our knowledge of spaceflight effects on developing mammals. Recent studies are revealing the first insights into how the space environment affects critical phases of mammalian reproduction and development, viz., those events surrounding fertilization, embryogenesis, pregnancy, birth, postnatal maturation and parental care. This review emphasizes fetal and early postnatal life, the developmental epochs for which the greatest amounts of mammalian spaceflight data have been amassed. The maternal-offspring system, the coordinated aggregate of mother and young comprising mammalian development, is of primary importance during these early, formative developmental phases. The existing research supports the view that biologically meaningful interactions between mothers and offspring are changed in the weightlessness of space. These changes may, in turn, cloud interpretations of spaceflight effects on developing offspring. Whereas studies of mid-pregnant rats in space have been extraordinarily successful, studies of young rat litters launched at 9 days of postnatal age or earlier, have been encumbered with problems related to the design of in-flight caging and compromised maternal-offspring interactions. Possibilities for mammalian birth in space, an event that has not yet transpired, are considered. In the aggregate, the results indicate a strong need for new studies of mammalian reproduction and development in space. Habitat development and systematic ground-based testing are important prerequisites to future research with young postnatal rodents in space. Together, the findings support the view that the environment within which young

  5. Mammalian development in space.

    PubMed

    Ronca, April E

    2003-01-01

    Life on Earth, and thus the reproductive and ontogenetic processes of all extant species and their ancestors, evolved under the constant influence of the Earth's l g gravitational field. These considerations raise important questions about the ability of mammals to reproduce and develop in space. In this chapter, I review the current state of our knowledge of spaceflight effects on developing mammals. Recent studies are revealing the first insights into how the space environment affects critical phases of mammalian reproduction and development, viz., those events surrounding fertilization, embryogenesis, pregnancy, birth, postnatal maturation and parental care. This review emphasizes fetal and early postnatal life, the developmental epochs for which the greatest amounts of mammalian spaceflight data have been amassed. The maternal-offspring system, the coordinated aggregate of mother and young comprising mammalian development, is of primary importance during these early, formative developmental phases. The existing research supports the view that biologically meaningful interactions between mothers and offspring are changed in the weightlessness of space. These changes may, in turn, cloud interpretations of spaceflight effects on developing offspring. Whereas studies of mid-pregnant rats in space have been extraordinarily successful, studies of young rat litters launched at 9 days of postnatal age or earlier, have been encumbered with problems related to the design of in-flight caging and compromised maternal-offspring interactions. Possibilities for mammalian birth in space, an event that has not yet transpired, are considered. In the aggregate, the results indicate a strong need for new studies of mammalian reproduction and development in space. Habitat development and systematic ground-based testing are important prerequisites to future research with young postnatal rodents in space. Together, the findings support the view that the environment within which young

  6. Mammalian enabled (Mena) is a critical regulator of cardiac function.

    PubMed

    Aguilar, Frédérick; Belmonte, Stephen L; Ram, Rashmi; Noujaim, Sami F; Dunaevsky, Olga; Protack, Tricia L; Jalife, Jose; Todd Massey, H; Gertler, Frank B; Blaxall, Burns C

    2011-05-01

    Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena(-/-)) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena(-/-) mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena(-/-) hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena(-/-) mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction.

  7. Effects of Tetrodotoxin on the Mammalian Cardiovascular System

    PubMed Central

    Zimmer, Thomas

    2010-01-01

    The human genome encodes nine functional voltage-gated Na+ channels. Three of them, namely Nav1.5, Nav1.8, and Nav1.9, are resistant to nanomolar concentrations of tetrodotoxin (TTX; IC50 ≥ 1 μM). The other isoforms, which are predominantly expressed in the skeletal muscle and nervous system, are highly sensitive to TTX (IC50 ~ 10 nM). During the last two decades, it has become evident that in addition to the major cardiac isoform Nav1.5, several of those TTX sensitive isoforms are expressed in the mammalian heart. Whereas immunohistochemical and electrophysiological methods demonstrated functional expression in various heart regions, the physiological importance of those isoforms for cardiac excitation in higher mammals is still debated. This review summarizes our knowledge on the systemic cardiovascular effects of TTX in animals and humans, with a special focus on cardiac excitation and performance at lower concentrations of this marine drug. Altogether, these data strongly suggest that TTX sensitive Na+ channels, detected more recently in various heart tissues, are not involved in excitation phenomena in the healthy adult heart of higher mammals. PMID:20411124

  8. INTERMEDIATE FILAMENTS IN SMOOTH MUSCLE

    PubMed Central

    Tang, Dale D.

    2008-01-01

    The intermediate filament (IF) network is one of the three cytoskeletal systems in smooth muscle. The type III IF proteins vimentin and desmin are major constituents of the network in smooth muscle cells and tissues. Lack of vimentin or desmin impairs contractile ability of various smooth muscle preparations, implying their important role for smooth muscle force development. The IF framework has long been viewed as a fixed cytostructure that solely provides mechanical integrity for the cell. However, recent studies suggest that the IF cytoskeleton is dynamic in mammalian cells in response to various external stimulation. In this review, the structure and biological properties of IF proteins in smooth muscle are summarized. The role of IF proteins in the modulation of smooth muscle force development and redistribution/translocation of signaling partners (such as p130 Crk-associated substrate, CAS) is depicted. This review also summarizes our latest understanding on how the IF network may be regulated in smooth muscle. PMID:18256275

  9. Diethyl hexyl phthalate-induced changes in insulin signaling molecules and the protective role of antioxidant vitamins in gastrocnemius muscle of adult male rat

    SciTech Connect

    Srinivasan, Chinnapaiyan; Khan, Adam Ismail; Balaji, Venkataraman; Selvaraj, Jayaraman; Balasubramanian, Karundevi

    2011-12-15

    Diethyl hexyl phthalate (DEHP) is an endocrine disruptor, it influences various organ systems in human beings and experimental animals. DEHP reduced the serum testosterone and increased the blood glucose, estradiol, T{sub 3} and T{sub 4} in rats. However, the effect of DEHP on insulin signaling and glucose oxidation in skeletal muscle is not known. Adult male albino rats were divided into four groups: Group I: Control; Groups II and III: DEHP treated (dissolved in olive oil at a dose of 10 and 100 mg/kg body weight, respectively, once daily through gastric intubation for 30 days); and Group IV: DEHP (100 mg/kg body weight) plus vitamins E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubation for 30 days. On completion of treatment, animals were euthanized and perfused (whole body); gastrocnemius muscle was dissected out and subjected to assessment of various parameters. DEHP treatment increased the H{sub 2}O{sub 2}, hydroxyl radical levels and lipid peroxidation which disrupt the membrane integrity and insulin receptor. DEHP impaired the insulin signal transduction, glucose uptake and oxidation through decreased expression of plasma membrane GLUT4, which may partly be responsible for the elevation of fasting blood glucose level. The present study suggests that DEHP exposure affects glucose oxidation in skeletal muscle and is mediated through enhanced lipid peroxidation, impaired insulin signaling and GLUT4 expression in plasma membrane. Antioxidant vitamins (C and E) have a protective role against the adverse effect of DEHP. -- Highlights: Black-Right-Pointing-Pointer DEHP treatment significantly decreased serum insulin and testosterone levels. Black-Right-Pointing-Pointer Increased ROS and decreased glucose uptake were observed in DEHP treated animals. Black-Right-Pointing-Pointer Impaired insulin signaling in gastrocnemius muscle was observed in DEHP treatment. Black

  10. Long-term hypoxia increases calcium affinity of BK channels in ovine fetal and adult cerebral artery smooth muscle.

    PubMed

    Tao, Xiaoxiao; Lin, Mike T; Thorington, Glyne U; Wilson, Sean M; Longo, Lawrence D; Hessinger, David A

    2015-04-01

    Acclimatization to high-altitude, long-term hypoxia (LTH) reportedly alters cerebral artery contraction-relaxation responses associated with changes in K(+) channel activity. We hypothesized that to maintain oxygenation during LTH, basilar arteries (BA) in the ovine adult and near-term fetus would show increased large-conductance Ca(2+) activated potassium (BK) channel activity. We measured BK channel activity, expression, and cell surface distribution by use of patch-clamp electrophysiology, flow cytometry, and confocal microscopy, respectively, in myocytes from normoxic control and LTH adult and near-term fetus BA. Electrophysiological data showed that BK channels in LTH myocytes exhibited 1) lowered Ca(2+) set points, 2) left-shifted activation voltages, and 3) longer dwell times. BK channels in LTH myocytes also appeared to be more dephosphorylated. These differences collectively make LTH BK channels more sensitive to activation. Studies using flow cytometry showed that the LTH fetus exhibited increased BK β1 subunit surface expression. In addition, in both fetal groups confocal microscopy revealed increased BK channel clustering and colocalization to myocyte lipid rafts. We conclude that increased BK channel activity in LTH BA occurred in association with increased channel affinity for Ca(2+) and left-shifted voltage activation. Increased cerebrovascular BK channel activity may be a mechanism by which LTH adult and near-term fetal sheep can acclimatize to long-term high altitude hypoxia. Our findings suggest that increasing BK channel activity in cerebral myocytes may be a therapeutic target to ameliorate the adverse effects of high altitude in adults or of intrauterine hypoxia in the fetus.

  11. Sex differences in whole body skeletal muscle mass measured by magnetic resonance imaging and its distribution in young Japanese adults

    PubMed Central

    Abe, T; Kearns, C; Fukunaga, T

    2003-01-01

    Objectives: To determine sex differences in the distribution of regional and total skeletal muscle (SM) using contiguous whole body magnetic resonance imaging (MRI) data, and to examine the relations between fat free mass (FFM) and total and regional SM masses. Methods: A total of 20 Japanese college students (10 women and 10 men) volunteered for the study. FFM was measured by two compartment densitometry. Whole body MRI images were prepared using a 1.5 T scanner. Contiguous transverse images with 1.0 cm slice thickness were obtained from the first cervical vertebra to the ankle joints. All MRI scans were segmented into four components (SM, subcutaneous adipose tissue, bone, and residual tissues). In each slice, the SM tissue cross sectional areas (CSAs) were digitised, and the muscle tissue volume per slice was calculated by multiplying muscle CSA by slice thickness. SM volume units (litres) were converted into mass units (kg) by multiplying the volumes by the assumed constant density (1.041 mg/ml) for SM. Results: The SM distribution pattern (shape of curve) from the contiguous whole body slices was essentially similar for the two sexes, with two large peaks and three smaller peaks (arms excluded). However, the largest peak was observed at the upper portion of the thigh for women and at the level of the shoulder for men. Men had larger (p<0.01) total and regional SM mass than women. All regional SM masses correlated highly (r = 0.90–0.99, p<0.01) with total SM mass. A strong positive correlation was observed between FFM and total and regional SM masses in both sexes (women, r = 0.95; men, r = 0.90; all p<0.01). As FFM increased, there was a corresponding increase in SM/FFM ratio for all subjects (r = 0.86, p<0.01). Conclusions: Sex differences in total SM/FFM ratio and regional SM distributions are associated with the degree of absolute FFM accumulation in men and women. PMID:14514537

  12. Effects of Pilates on muscle strength, postural balance and quality of life of older adults: a randomized, controlled, clinical trial

    PubMed Central

    Campos de Oliveira, Laís; Gonçalves de Oliveira, Raphael; Pires-Oliveira, Deise Aparecida de Almeida

    2015-01-01

    [Purpose] The aim of the present study was to determine the effects of Pilates on lower leg strength, postural balance and the health-related quality of life (HRQoL) of older adults. [Subjects and Methods] Thirty-two older adults were randomly allocated either to the experimental group (EG, n = 16; mean age, 63.62 ± 1.02 years), which performed two sessions of Pilates per week for 12 weeks, or to the control group (CG, n = 16; mean age, 64.21 ± 0.80), which performed two sessions of static stretching per week for 12 weeks. The following evaluations were performed before and after the interventions: isokinetic torque of knee extensors and flexors at 300°/s, the Timed Up and Go (TUG) test, the Berg Balance Scale, and the Health Survey assessment (SF-36). [Results] In the intra-group analysis, the EG demonstrated significant improvement in all variables. In the inter-group analysis, the EG demonstrated significant improvement in most variables. [Conclusion] Pilates exercises led to significant improvement in isokinetic torque of the knee extensors and flexors, postural balance and aspects of the health-related quality of life of older adults. PMID:25931749

  13. The mouse muscle creatine kinase promoter faithfully drives reporter gene expression in transgenic Xenopus laevis.

    PubMed

    Lim, Wayland; Neff, Eric S; Furlow, J David

    2004-06-17

    Developing Xenopus laevis experience two periods of muscle differentiation, once during embryogenesis and again at metamorphosis. During metamorphosis, thyroid hormone induces both muscle growth in the limbs and muscle death in the tail. In mammals, the muscle creatine kinase (MCK) gene is activated during the differentiation from myoblasts to myocytes and has served as both a marker for muscle development and to drive transgene expression in transgenic mice. Transcriptional control elements are generally highly conserved throughout evolution, potentially allowing mouse promoter use in transgenic X. laevis. This paper compares endogenous X. laevis MCK gene expression and the mouse MCK (mMCK) promoter driving a green fluorescent protein reporter in transgenic X. laevis. The mMCK promoter demonstrated strong skeletal muscle-specific transgene expression in both the juvenile tadpole and adult frog. Therefore, our results clearly demonstrate the functional conservation of regulatory sequenc