Plasticity and Adaptation to Training and Disuse PDF

Plasticity and adaptation to training and disuse Dr. Frederic von Wegner WARNING  This material has been reproduced and commun...

Plasticity and adaptation to training and disuse Dr. Frederic von Wegner WARNING  This material has been reproduced and communicated to you by or on behalf of the University of New South Wales in accordance with section 113P of the Copyright Act 1968 (Act).  The material in this communication may be subject to copyright under the Act. Any further reproduction or communication of this material by you may be the subject of copyright protection under the Act.  Do not remove this notice Learning objectives - what is skeletal muscle fibre plasticity? - name intracellular signaling pathways involved in plasticity and how they are linked - name experimental procedures to induce fibre plasticity - describe adaptation mechanisms to different types of exercise - describe changes in the nervous system contributing to training effects Skeletal muscle fibre plasticity cellular mechanisms  External & internal factors: hypertrophy vs. atrophy behaviour: elimination of microgravity, - training vs. disuse synergists hindlimb suspension experimental: - overload, electrical stimulation vs. unloading, denervation internal/hormonal: - androgens (testosterone) beta-agonists (adrenaline) IGF-1 vs. myostatin, glucocorticoids external (drugs): - beta-agonists, androgens growth hormones vs. glucocorticoids Blaauw, 2013  External & internal factors: hypertrophy vs. atrophy behaviour: elimination of microgravity, - training vs. disuse synergists hindlimb suspension experimental: - overload, electrical stimulation vs. unloading, denervation internal/hormonal: - androgens (testosterone) beta-agonists (adrenaline) IGF-1 vs. myostatin, glucocorticoids external (drugs): - beta-agonists, androgens growth hormones vs. remember glucocorticoids doping? Blaauw, 2013  External & internal factors: fast vs. slow fibre types CLFS: chronic low-frequency electrical stimulation Blaauw, 2013  Experimental fibre type transition slow fast - electrical stim. of rat fast fibre - time-to-peak (TTP) ~ fibre type (Prac 5!) - only low-frequency stim. achieves fast (low TTP) to slow (high TTP) transition Blaauw, 2013  Experimental fibre type transition slow slow fast fast - electrical stim. of rat fast fibre - same number of pulses/day - time-to-peak (TTP) ~ fibre type (Prac 5!) => only low freq. stim (10 Hz) achieves - only low-frequency stim. achieves fast-to-slow transition fast (low TTP) to slow (high TTP) transition Blaauw, 2013  Experimental fibre type transition tetanus - force-frequency curve (Prac-5!) - fast-like behaviour: - higher fusion freq. slow - lower twitch-tetanus ratio => only low freq. stim ( the fast fibre (FDL) will turn into a slow fibre phenotype - also, the intracellular biochemistry, e.g. Ca2+ buffers, adapt to the slow type Buller, 1960  Observed fibre type transitions masticatory - myosin heavy chain transitions observed in experiments - gene transcription and protein translation seems to be constrained (not any transition is possible) extraocular - the combination of factors can increase the range of plasticity, e.g. hyperthyroidism and mech. unloading: 1 → 2B Schiaffino, 2011 Plasticity and training Adaptation to exercise Sensing ‘muscle stress’: - 4 stressors: mechanical load, neuronal activation, hormonal adjustment metabolic disturbance (Hoppeler, 2016) - a) resistance/strength training => mechanical stress dominates - b) endurance training => metabolic changes more pronounced - both: the associated nerve impulses and Ca2+ transients start molecular events that lead to future adaption to new exposures to the same kind of ‘stress’ Adaptation to exercise Sensing ‘muscle stress’: - 4 stressors: mechanical load, neuronal activation, hormonal adjustment metabolic disturbance (Hoppeler, 2016) - a) resistance/strength training => mechanical stress dominates - b) endurance training => metabolic changes more pronounced - both: the associated nerve impulses and Ca2+ transients start molecular events that lead to future adaption to new exposures to the same kind of ‘stress’ - Questions: - how can ‘running around’ lead to the formation of new mitochondria? - how can a few dozen contractions of our arm muscles (+weight) make that muscle grow!? Fibre type adaptation in athletes - % ST: proportion of slow-twitch fibres - muscles adapt their fibre type composition to specific requirements elite power lifter elite marathon 85% type II 90% type I mATPase (4,2), Whyte, The Physiol. of Traning Tesch, 1985 Endurance vs. resistance exercise Endurance Exercise: - repeated low-intensity contractions - low force, low fatigue, aerobic system - cycling, swimming,... - typical transitions: type IIX → IIA - fast IIX fibres → slower (more economical) II A fibres slow I fibres → faster type I fibres - myosin light chain changes type II: fast MLC → slow MLC type I: slow MLC → fast MLC - mitochondrial biogenesis: PGC-1α (increase in size, then number) => ‘aerobic fitness’ Qaisar, 2016 Endurance vs. resistance exercise Endurance Exercise: Resistance Exercise: - repeated low-intensity contractions - low-frequency, high-intensity contract. - low force, low fatigue, aerobic system (e.g. 80% MVC) - cycling, swimming,... - type II hypertrophy: - typical transitions: type IIX → IIA actin-myosin synthesis, more myofibrils - fast IIX fibres → slower (more in parallel (cross-sect. area ↑) economical) II A fibres - protein synthesis and degradation slow I fibres → faster type I fibres increase → hypertrophy delayed - myosin light chain changes re-structuring of the muscle type II: fast MLC → slow MLC - mechanical forces activate focal type I: slow MLC → fast MLC adhesion kinase (FAK) → activation - mitochondrial biogenesis: PGC-1α of the mTOR pathway (increase in size, then number) => ‘aerobic fitness’ Qaisar, 2016 resistance: endurance: protein gene translation expression Qaisar, 2016 Simplified model: endurance vs. strength - ‘endurance’ pathway: 1. low frequency stimulation and sustained contractions 2a. Ca2+ / calmodulin / CaM-Kinase 2b. AMPK ‘master switch’ (AMP/ATP ↑) 3. mitochondrial proliferation ↑ 4. slow fiber programs - resistance (‘strength’) pathway: 1. high-frequency stimulation 2. AMPK ‘master switch’ (AMP/ATP ↓) 2. mTOR Hoppeler, 2011 Changes due to inactivity - muscle biopsy after 37 days of bed rest - myosin ATPase staining (A) - B-D: mRNA autoradiography B: MHC-β (slow) transcript C: MHC-2A transcript D: MHC-2X transcript 11: MHC-1 protein, but MHC-2X mRNA 12: + MHC-2X, + MHC-2A mRNA 13: MHC-2X and MHC-β (slow) mRNA => transitional fibres after rest 1 → 2X Andersen, 1999 Fibre type changes due to inactivity slow fibres ↓ fast fibres (2X) ↑ Andersen, 1999 Neural plasticity and exercise Neural drive and neural enhancement - what happens during early training? - muscle fibre protein synthesis increases after the first training session but: hypertrophy needs weeks to occur - however, training increases max. strength within a few days (knee extensors, wrist flexors, elbow extensors…, Gabriel 2006) - strength after rest periods: after 35 contractions in 1 day, strength increases were present after 2 weeks rest comparison with biochemical data: metabolic changes unlikely => altered neural drive (increasing sEMG amplitudes without hypertrophy) => peripheral / central? => nervous system ‘learned’ maximal activation Gabriel 2006 Neural plasticity and training - motor unit firing rate - strength training => increases in MVC motor unit firing rate ipsi- and contralateral to training side - probably important in early adaptation (e.g. first week) after that: motor program optimization with variable changes in firing rate - firing patterns: doublets often occur at contraction onset, at high contraction speeds => rapid rise in Ca2+ possibly optimized during early training (hypothesis) - Motor Unit synchronisation? Hypothesis unproven due to methodological limitations (e.g. sEMG) Gabriel 2006 Neural plasticity and training - spinal changes - increased motor neuron excitability due to (voluntary) suppression of descending inhibition - measured as increased H-reflex (V-reflex during contraction) - learning experiments (operant conditioning): stretch reflex changes with verbal command given (Carp, 1995) Gabriel 2006 Neural plasticity and training - spinal changes - increased motor neuron excitability due to (voluntary) suppression of descending inhibition - measured as increased H-reflex (V-reflex during contraction) - learning experiments (operant conditioning): stretch reflex changes with verbal command given (Carp, 1995) - motor cortex output - motor imagery experiments (mental practice, no movement) - motor cortex activation can be measured (fMRI, TMS) - imagined max. efforts increase real MVC force (Bowers 1966) - depends on the target muscle, role: rehabilitation > sports Gabriel 2006 Neural plasticity and training - cross transfer - motor neuron facilitation by activation of the contralateral heteronymous muscle (Schantz 1989) example: (short) contraction left knee flexor => right knee ext. + contraction left knee ext. => right knee ext. - - more effective with contralateral eccentric contraction - neural effect likely, no changes in biochemical properties of ipsilat. muscle (spinal, cortical?) Baehr, Top. diagnosis in Neurology Neural plasticity and training - agonist-antagonist-interaction - simplified model: training reduces antagonist co-activation antagonist just counteracts agonist’s action - one convincing study using knee ext. strength training showed MVC force reduction in antagonist => optimizes force production - other target: joint stability / mechanical stress for joint stabilization, antagonist co-activation may be optimal e.g. increased M. triceps brachii strength and co-activation in elbow-flexor training => task-dependence, no definitive conclusions yet Baehr, Top. diagnosis in Neurology Summary 1. Adaptation to training happens across all levels: brain, spinal cord, muscle 2. muscle fiber plasticity is regulated by mechanical forces (neuro-)electrical input hormones 3. the current model for cellular pathways for endurance and resistance training: resistance: mTOR – translation / protein synth. / hypertrophy – fast fibre programs endurance: Ca2+, ATP (AMPK) – gene expression – slow fibre programs 4. neural adaptation faster than fibre re-programming motor unit: excitability changes and firing rate adaptation brain: motor program learning / training Thank you!