Soniya Lohana
Ist MPT
Department of Sports Physiotherapy
2/24/2020
1
MusclePlasticity
2/24/2020
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MusclePlasticity
CONTENTS
 Introduction
 Concept of Muscle Plasticity
 Structure of a Skeletal Muscle
 Types of Muscle Fibers
 Chronic Low Frequency stimulation
 Time course of muscle fiber transformation
 Changes Induced by chronic low frequency stimulation.
 Evidences
 References
2/24/2020
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MusclePlasticity
HISTORY
 “Plasticity of Muscle” – John Eccles, 1979
 Muscle Ontogeny – structural, functional, metabolic and
molecular heterogenicity, above all their malleability by
modulation of neural input and usage.
 Research states that motor nerves exert a phenotypic
influence on the muscles they innervate.
2/24/2020
4
MusclePlasticity
DEFINITION
 Skeletal muscle plasticity - regards to modification of
skeletal structures in responses to environmental
change.
 It also refers to dynamic ability of a muscle to adapt,
when its level of use is increased.
 In response to demands imposed on muscle, its
structure, biochemical and physiological characteristics
change (1982)
2/24/2020
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Figure 1
Transmission electron micrograph of a skeletal muscle sarcomere. The Z-disc defines the
boundary of the sarcomere. The striations are formed by the highly organized
arrangement of thick and thin filaments. Scale bar represents 500 nm.
TYPES OF MUSCLE FIBRES
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ELECTRICAL STIMULATION
 Chronic Electrical Stimulation provide one of the
cleanest views of muscle adaptation due to increased
use.
 Muscles performing different tasks in addition to having
different muscle architecture respond to different
electrical input.
 Slow twitch fibres – low frequency currents
 Fast twitch fibres – high frequency bursts
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CHRONIC LOW-FREQUENCY
STIMULATION
fast-twitch slow-twitch
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indirect electrical stimulation
Tonic, low frequency
Brown (1984)
TIME COURSE OF MUSCLE FIBRE
TRANSFORMATION
 If low frequency stimulation is applied for 8-24
hours per day
 Total transformation time period - about 8 weeks
 Changes that occur are
- change in contractile properties
- metabolic changes
- circulatory changes
- structural changes
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COMPONENTS OF MUSCLES WHICH GET
MODIFIED
 Architecture of the muscle
 Fiber type distribution
 Fiber Diameter
 Fiber length
 Tendon length
 Myosin heavy chain profile
 Mitochondrial distribution
 Capillary Density
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IN 2-3 HOURS FOLLOWING STIMULATION
The earliest observed changes occur
within a few hours after the onset of
stimulation where swelling begins to
occur in the sarcoplasmic reticulum (SR)
membrane network.
Significance of this morphological change
is not clear but routinely observed.
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IN 2-12 DAYS FOLLOWING ELECTRICAL
STIMULATION
 Size and number of mitochondria
increase
Volume % of mitochondria increases
The oxidative enzyme activity
also increases and in combination with
increased blood flow, this leads to increased
muscle metabolic activity.
 Decrease in muscle fatigability
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Increase in number of capillaries
per square mm
(ANGIOGENISIS)
Increase in total blood flow
Increase in total oxygen
consumption
Increased oxidative enzymes and
muscle metabolic activity
Decrease in muscle fatiguability
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IN 14 DAYS FOLLOWING ELECTRICAL
STIMULATION
 Z band increases in width and there is decrease in
amount and activity of calcium ATPase
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IN 28 DAYS FOLLOWING ELECTRICAL
STIMULATION
 Myosin profile altered with different myosin monomers
incorporating into a single filament
(LC1f, LC2f & LC3f LC1s LC2s)
 Heavy chain profile altered
 Fast muscle fibres become more like a slow muscle fibre
 Muscle mass and fibre area decreases
 Z band- full width
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Title Methodology Conclusion
Effects of Long-Term
Stimulation on
Skeletal Muscle
Phenotype
Expression and
Collagen/Fibrillin
Distribution
Dennis R. Trumble,
Changping Duan, and
James A. Magovern
Latissimus dorsi (LD) of
eight rabbits
were used to study
muscular adaptation to
long-term electrical
conditioning. Muscles
were
conditioned using burst
stimuli delivered over 6
or 12 weeks.
Contralateral LD were
used as
control.
Stimulation improved
endurance capacity due
to increased % CSA
occupied by
slow-twitch oxidative,
type I collagen and
fibrillin. The data
suggest that muscular
adaptation
to long-term stimulation
includes both alterations
in fiber type expression
and remodeling of
the extracellular matrix.
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Title Methodology Conclusion
Muscle Plasticity
Response to training
and detraining
- Anne Bruton
All skeletal muscles have
adaptive potential,
in response to
environmental change.
Increased and
reduced activity are two
of the common
environmental
changes that
physiotherapists see in
clinical practice
(eg muscle training and
detraining). The purpose
of this
article is to review the
literature surrounding
these two areas.
Although muscle
response to altered
patterns of activity has
been extensively
studied, there are still
many areas of
uncertainty as
individuality
of responses to
exercise changes. The
gene environment
interaction is complex,
but
it is possible that
genotype may determine
this phenotypic response
2/24/2020
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CHANGES INDUCED BY CHRONIC LOW-
FREQUENCY STIMULATION
 The earliest studies have also revealed that CLFS
in the rabbit leads to a reduction in muscle bulk and
tetanic tension
 This loss in muscle bulk is due to a reduction of
fiber diameter of the largest most fatigable muscle
fibers that are exposed to sudden excessive
activity.
 These observations were obtained from chronically
stimulated rabbit extensor digitorum longus (EDL)
and tibialis anterior (TA) muscles.
2/24/2020
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 After long-term stimulation, two main functional
changes were observed: slowing of the time-
courses of contraction and relaxation; and
increased fatigue resistance.
 Many of the functional changes of the stimulated
muscle reflect profound alterations in gene
expression leading to a transformation of the
muscle fibers phenotype.
.
2/24/2020
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Title Methodology Conclusion
Chronic
neuromuscular
electrical
stimulation improves
muscle mass
and insulin sensitivity
in a mouse
model
Adiel Lotri-Koffi1 et al
Investigation on a mouse
model of in-vivo non-
invasive chronic NMES
on muscle mass, insulin
sensitivity and arterial
blood pressure was done.
23 mice underwent
unilateral NMES or sham
training over 2.5 weeks
while anesthetized by
isoflurane.
After training, muscle
mass increased in
NMES
vs. sham. Insulin
sensitivity improved in
NMES vs. sham. The
metabolic benefit of
NMES
training could be of
great utility in patients
with chronic disease.
Moreover, the clinical-
like mouse model of
NMES is an effective
tool to investigate the
systemic effects of
local muscle
strengthening.
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TITLE METHODOLOGY CONCLUSION
Effect of Intermittent
Low-Frequency
Electrical Stimulation
on the Rat
Gastrocnemius Muscle
Arata Tsutaki,1 Riki
Ogasawara et al
Low-frequency
neuromuscular electrical
stimulation (NMES) has
been used as an
endurance exercise
model
Using Sprague-Dawley
rats, 1 bout of exercise
(with dissection done
immediately (Post0) and
3 h (Post3) after
exercise) and another 6
sessions of training were
performed. All
experimental groups
consisted of high- and
low-frequency
stimulation (HFS:
100 Hz; LFS: 10 Hz).
Present study
demonstrates that
muscle activation by
electrical stimulation
recruits type II fibers
independently of
frequency and that
electrical stimulation
without high force
generation results in
muscle hypertrophy.
These findings may be
applicable to both
athletic conditioning as
well as to clinical care for
sports injuries and
muscle atrophy
Title Purpose Conclusion
The Contribution of
Neuromuscular
Stimulation in
Elucidating Muscle
Plasticity Revisited
Dirk Pette, Gerta
Vrbová
As reflected by induced
changes in the
metabolic properties,
protein profiles of the
contractile machinery
and elements of the
Ca2+-regulatory
system, all essential
components of the
muscle fibre undergo
pronounced changes in
their properties that
ultimately lead to their
reversible
transformation from
fast-to-slow phenotype.
The understanding of
the adaptive potential of
muscle can be taken
advantage of for
repairing muscle
damage in various
muscle diseases. In
addition it can be used
to prevent muscle
wasting during inactivity
and aging.
2/24/2020
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Title Methodology Conclusion
Coregulator-mediated
control of skeletal
muscle plasticity – a
mini-review
Svenia Schnyder,
Barbara Kupr, and
Christoph Handschin
In skeletal muscle,
several coregulators
have been identified as
potent regulators of
metabolic and
myofibrillar plasticity In
this mini-review, the
regulation, function and
physiological
significance of these
coregulators in skeletal
muscle biology are
discussed.
The synergistic and
antagonizing effects of
coregulators, could also
help to identify potential
therapeutic targets in
the treatment of
metabolic and muscle
diseases.
For eg: chronic
administration of a
synthetic class IIa
HDAC inhibitor
enhanced muscle
endurance, and
ameliorated systemic
lipid and glucose
handling
2/24/2020
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MusclePlasticity
TITLE MEATHEDOLOGY CONCLUSION
Beneficial effects of
chronic low-frequency
stimulation of thigh
muscles in patients with
advanced chronic heart
failure.
Nuhr MJ1, Pette D et al
Patients with chronic
heart failure (CHF)
exhibit detrimental
changes in skeletal
muscle that contribute
to their impaired
physical performance.
This study investigates
the possibility of
counteracting these
changes by chronic low-
frequency electrical
stimulation (CLFS) of
left and right thigh
muscles.
Our results suggest that
CLFS is a suitable
treatment to counteract
detrimental changes in
skeletal muscle and to
increase exercise
capacity in patients with
severe CHF
REFERENCES
 Chromiak JA, Antonio J. Skeletal muscle plasticity. InEssentials
of sports nutrition and supplements 2008 (pp. 21-52). Humana
Press.
 Nuhr MJ, Pette D, Berger R, Quittan M, Crevenna R, Huelsman
M, Wiesinger GF, Moser P, Fialka-Moser V, Pacher R. Beneficial
effects of chronic low-frequency stimulation of thigh muscles in
patients with advanced chronic heart failure. European heart
journal. 2004 Jan 1;25(2):136-43.
 Trumble DR, Duan C, Magovern JA. Effects of long-term
stimulation on skeletal muscle phenotype expression and
collagen/fibrillin distribution. BAM-PADOVA-. 2001;11(2):91-8.
 Tsutaki A, Ogasawara R, Kobayashi K, Lee K, Kouzaki K,
Nakazato K. Effect of intermittent low-frequency electrical
stimulation on the rat gastrocnemius muscle. BioMed research
international. 2013;2013.
2/24/2020
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 Andrew J. Robinson. Clinical Electrotherapy, Chapter 8, Muscular changes
in responses to electrical stimulation.
 Trumble DR, Duan C, Magovern JA. Effects of long-term stimulation on
skeletal muscle phenotype expression and collagen/fibrillin distribution.
BAM-PADOVA-. 2001;11(2):91-8.
 Pette D, Vrbová G. The contribution of neuromuscular stimulation in
elucidating muscle plasticity revisited. European journal of translational
myology. 2017 Feb 24;27(1).
 Schnyder S, Kupr B, Handschin C. Coregulator-mediated control of
skeletal muscle plasticity–a mini-review. Biochimie. 2017 May 1;136:49-
54.
 Bruton A. Muscle plasticity: response to training and detraining.
Physiotherapy. 2002 Jul 1;88(7):398-408.
 Lotri-Koffi A, Pauly M, Lemarié E, Godin-Ribuot D, Tamisier R, Pépin JL,
Vivodtzev I. Chronic neuromuscular electrical stimulation improves muscle
mass and insulin sensitivity in a mouse model. Scientific reports. 2019
May 10;9(1):7252.
2/24/2020
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MusclePlasticity
THANKYOU
2/24/2020
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MusclePlasticity

Muscle plasticity

  • 1.
    Soniya Lohana Ist MPT Departmentof Sports Physiotherapy 2/24/2020 1 MusclePlasticity
  • 2.
  • 3.
    CONTENTS  Introduction  Conceptof Muscle Plasticity  Structure of a Skeletal Muscle  Types of Muscle Fibers  Chronic Low Frequency stimulation  Time course of muscle fiber transformation  Changes Induced by chronic low frequency stimulation.  Evidences  References 2/24/2020 3 MusclePlasticity
  • 4.
    HISTORY  “Plasticity ofMuscle” – John Eccles, 1979  Muscle Ontogeny – structural, functional, metabolic and molecular heterogenicity, above all their malleability by modulation of neural input and usage.  Research states that motor nerves exert a phenotypic influence on the muscles they innervate. 2/24/2020 4 MusclePlasticity
  • 5.
    DEFINITION  Skeletal muscleplasticity - regards to modification of skeletal structures in responses to environmental change.  It also refers to dynamic ability of a muscle to adapt, when its level of use is increased.  In response to demands imposed on muscle, its structure, biochemical and physiological characteristics change (1982) 2/24/2020 5 MusclePlasticity
  • 6.
  • 7.
    2/24/2020 7 MusclePlasticity Figure 1 Transmission electronmicrograph of a skeletal muscle sarcomere. The Z-disc defines the boundary of the sarcomere. The striations are formed by the highly organized arrangement of thick and thin filaments. Scale bar represents 500 nm.
  • 8.
    TYPES OF MUSCLEFIBRES 2/24/2020 8 MusclePlasticity
  • 9.
  • 10.
  • 11.
  • 12.
    ELECTRICAL STIMULATION  ChronicElectrical Stimulation provide one of the cleanest views of muscle adaptation due to increased use.  Muscles performing different tasks in addition to having different muscle architecture respond to different electrical input.  Slow twitch fibres – low frequency currents  Fast twitch fibres – high frequency bursts 2/24/2020 12 MusclePlasticity
  • 13.
  • 14.
    TIME COURSE OFMUSCLE FIBRE TRANSFORMATION  If low frequency stimulation is applied for 8-24 hours per day  Total transformation time period - about 8 weeks  Changes that occur are - change in contractile properties - metabolic changes - circulatory changes - structural changes 2/24/2020 14 MusclePlasticity
  • 15.
    COMPONENTS OF MUSCLESWHICH GET MODIFIED  Architecture of the muscle  Fiber type distribution  Fiber Diameter  Fiber length  Tendon length  Myosin heavy chain profile  Mitochondrial distribution  Capillary Density 2/24/2020 15 MusclePlasticity
  • 16.
    IN 2-3 HOURSFOLLOWING STIMULATION The earliest observed changes occur within a few hours after the onset of stimulation where swelling begins to occur in the sarcoplasmic reticulum (SR) membrane network. Significance of this morphological change is not clear but routinely observed. 2/24/2020 16 MusclePlasticity
  • 17.
    IN 2-12 DAYSFOLLOWING ELECTRICAL STIMULATION  Size and number of mitochondria increase Volume % of mitochondria increases The oxidative enzyme activity also increases and in combination with increased blood flow, this leads to increased muscle metabolic activity.  Decrease in muscle fatigability 2/24/2020 17 MusclePlasticity
  • 18.
    Increase in numberof capillaries per square mm (ANGIOGENISIS) Increase in total blood flow Increase in total oxygen consumption Increased oxidative enzymes and muscle metabolic activity Decrease in muscle fatiguability 2/24/2020 18 MusclePlasticity
  • 19.
    IN 14 DAYSFOLLOWING ELECTRICAL STIMULATION  Z band increases in width and there is decrease in amount and activity of calcium ATPase 2/24/2020 19 MusclePlasticity
  • 20.
    IN 28 DAYSFOLLOWING ELECTRICAL STIMULATION  Myosin profile altered with different myosin monomers incorporating into a single filament (LC1f, LC2f & LC3f LC1s LC2s)  Heavy chain profile altered  Fast muscle fibres become more like a slow muscle fibre  Muscle mass and fibre area decreases  Z band- full width 2/24/2020 20 MusclePlasticity
  • 21.
  • 22.
  • 23.
    Title Methodology Conclusion Effectsof Long-Term Stimulation on Skeletal Muscle Phenotype Expression and Collagen/Fibrillin Distribution Dennis R. Trumble, Changping Duan, and James A. Magovern Latissimus dorsi (LD) of eight rabbits were used to study muscular adaptation to long-term electrical conditioning. Muscles were conditioned using burst stimuli delivered over 6 or 12 weeks. Contralateral LD were used as control. Stimulation improved endurance capacity due to increased % CSA occupied by slow-twitch oxidative, type I collagen and fibrillin. The data suggest that muscular adaptation to long-term stimulation includes both alterations in fiber type expression and remodeling of the extracellular matrix. 2/24/2020 23 MusclePlasticity
  • 24.
  • 25.
    Title Methodology Conclusion MusclePlasticity Response to training and detraining - Anne Bruton All skeletal muscles have adaptive potential, in response to environmental change. Increased and reduced activity are two of the common environmental changes that physiotherapists see in clinical practice (eg muscle training and detraining). The purpose of this article is to review the literature surrounding these two areas. Although muscle response to altered patterns of activity has been extensively studied, there are still many areas of uncertainty as individuality of responses to exercise changes. The gene environment interaction is complex, but it is possible that genotype may determine this phenotypic response 2/24/2020 25 MusclePlasticity
  • 26.
  • 27.
    CHANGES INDUCED BYCHRONIC LOW- FREQUENCY STIMULATION  The earliest studies have also revealed that CLFS in the rabbit leads to a reduction in muscle bulk and tetanic tension  This loss in muscle bulk is due to a reduction of fiber diameter of the largest most fatigable muscle fibers that are exposed to sudden excessive activity.  These observations were obtained from chronically stimulated rabbit extensor digitorum longus (EDL) and tibialis anterior (TA) muscles. 2/24/2020 27 MusclePlasticity
  • 28.
     After long-termstimulation, two main functional changes were observed: slowing of the time- courses of contraction and relaxation; and increased fatigue resistance.  Many of the functional changes of the stimulated muscle reflect profound alterations in gene expression leading to a transformation of the muscle fibers phenotype. . 2/24/2020 28 MusclePlasticity
  • 29.
    Title Methodology Conclusion Chronic neuromuscular electrical stimulationimproves muscle mass and insulin sensitivity in a mouse model Adiel Lotri-Koffi1 et al Investigation on a mouse model of in-vivo non- invasive chronic NMES on muscle mass, insulin sensitivity and arterial blood pressure was done. 23 mice underwent unilateral NMES or sham training over 2.5 weeks while anesthetized by isoflurane. After training, muscle mass increased in NMES vs. sham. Insulin sensitivity improved in NMES vs. sham. The metabolic benefit of NMES training could be of great utility in patients with chronic disease. Moreover, the clinical- like mouse model of NMES is an effective tool to investigate the systemic effects of local muscle strengthening. 2/24/2020 29 MusclePlasticity
  • 30.
    TITLE METHODOLOGY CONCLUSION Effectof Intermittent Low-Frequency Electrical Stimulation on the Rat Gastrocnemius Muscle Arata Tsutaki,1 Riki Ogasawara et al Low-frequency neuromuscular electrical stimulation (NMES) has been used as an endurance exercise model Using Sprague-Dawley rats, 1 bout of exercise (with dissection done immediately (Post0) and 3 h (Post3) after exercise) and another 6 sessions of training were performed. All experimental groups consisted of high- and low-frequency stimulation (HFS: 100 Hz; LFS: 10 Hz). Present study demonstrates that muscle activation by electrical stimulation recruits type II fibers independently of frequency and that electrical stimulation without high force generation results in muscle hypertrophy. These findings may be applicable to both athletic conditioning as well as to clinical care for sports injuries and muscle atrophy
  • 31.
    Title Purpose Conclusion TheContribution of Neuromuscular Stimulation in Elucidating Muscle Plasticity Revisited Dirk Pette, Gerta Vrbová As reflected by induced changes in the metabolic properties, protein profiles of the contractile machinery and elements of the Ca2+-regulatory system, all essential components of the muscle fibre undergo pronounced changes in their properties that ultimately lead to their reversible transformation from fast-to-slow phenotype. The understanding of the adaptive potential of muscle can be taken advantage of for repairing muscle damage in various muscle diseases. In addition it can be used to prevent muscle wasting during inactivity and aging. 2/24/2020 31 MusclePlasticity
  • 32.
    Title Methodology Conclusion Coregulator-mediated controlof skeletal muscle plasticity – a mini-review Svenia Schnyder, Barbara Kupr, and Christoph Handschin In skeletal muscle, several coregulators have been identified as potent regulators of metabolic and myofibrillar plasticity In this mini-review, the regulation, function and physiological significance of these coregulators in skeletal muscle biology are discussed. The synergistic and antagonizing effects of coregulators, could also help to identify potential therapeutic targets in the treatment of metabolic and muscle diseases. For eg: chronic administration of a synthetic class IIa HDAC inhibitor enhanced muscle endurance, and ameliorated systemic lipid and glucose handling 2/24/2020 32 MusclePlasticity
  • 33.
    TITLE MEATHEDOLOGY CONCLUSION Beneficialeffects of chronic low-frequency stimulation of thigh muscles in patients with advanced chronic heart failure. Nuhr MJ1, Pette D et al Patients with chronic heart failure (CHF) exhibit detrimental changes in skeletal muscle that contribute to their impaired physical performance. This study investigates the possibility of counteracting these changes by chronic low- frequency electrical stimulation (CLFS) of left and right thigh muscles. Our results suggest that CLFS is a suitable treatment to counteract detrimental changes in skeletal muscle and to increase exercise capacity in patients with severe CHF
  • 34.
    REFERENCES  Chromiak JA,Antonio J. Skeletal muscle plasticity. InEssentials of sports nutrition and supplements 2008 (pp. 21-52). Humana Press.  Nuhr MJ, Pette D, Berger R, Quittan M, Crevenna R, Huelsman M, Wiesinger GF, Moser P, Fialka-Moser V, Pacher R. Beneficial effects of chronic low-frequency stimulation of thigh muscles in patients with advanced chronic heart failure. European heart journal. 2004 Jan 1;25(2):136-43.  Trumble DR, Duan C, Magovern JA. Effects of long-term stimulation on skeletal muscle phenotype expression and collagen/fibrillin distribution. BAM-PADOVA-. 2001;11(2):91-8.  Tsutaki A, Ogasawara R, Kobayashi K, Lee K, Kouzaki K, Nakazato K. Effect of intermittent low-frequency electrical stimulation on the rat gastrocnemius muscle. BioMed research international. 2013;2013. 2/24/2020 34 MusclePlasticity
  • 35.
     Andrew J.Robinson. Clinical Electrotherapy, Chapter 8, Muscular changes in responses to electrical stimulation.  Trumble DR, Duan C, Magovern JA. Effects of long-term stimulation on skeletal muscle phenotype expression and collagen/fibrillin distribution. BAM-PADOVA-. 2001;11(2):91-8.  Pette D, Vrbová G. The contribution of neuromuscular stimulation in elucidating muscle plasticity revisited. European journal of translational myology. 2017 Feb 24;27(1).  Schnyder S, Kupr B, Handschin C. Coregulator-mediated control of skeletal muscle plasticity–a mini-review. Biochimie. 2017 May 1;136:49- 54.  Bruton A. Muscle plasticity: response to training and detraining. Physiotherapy. 2002 Jul 1;88(7):398-408.  Lotri-Koffi A, Pauly M, Lemarié E, Godin-Ribuot D, Tamisier R, Pépin JL, Vivodtzev I. Chronic neuromuscular electrical stimulation improves muscle mass and insulin sensitivity in a mouse model. Scientific reports. 2019 May 10;9(1):7252. 2/24/2020 35 MusclePlasticity
  • 36.