Smoke‐induced neuromuscular junction degeneration precedes the fibre type shift and atrophy in chronic obstructive pulmonary disease

Kapchinsky, Sophia; Vuda, Madhusudanarao; Miguez, Kayla; Elkrief, Daren; Souza, Angela Rico de; Baglole, Carolyn J.; Aare, Sudhakar; MacMillan, Norah J.; Baril, Jacinthe; Rozakis, Paul; Sonjak, Vita; Pion, Charlotte H.; Aubertin‐Leheudre, Mylène; Morais, José A.; Jagoe, R. Thomas; Bourbeau, Jean; Taivassalo, Tanja; Hepple, Russell T.

doi:10.1113/jp275558

Cited by 38 publications

(60 citation statements)

References 82 publications

(163 reference statements)

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“…These changes were accompanied by reductions in RTD, both absolute and relative to peak torque, reflecting a shift towards slower contractile properties in the intact limb. This is in contrast to the results of short-term disuse studies in both healthy control subjects and pathological populations, which have reported a shift towards faster contractile properties owing to a greater expression of fast-contracting myosin heavy-chain (MHC) isoforms (Bamman et al, 1998;Kapchinsky et al, 2018;Trappe et al, 2004). The results of the present study therefore provide new evidence that changes in intrinsic contractile properties with longterm disuse are more characteristic of ageing muscle, which also displays a slowing of the contractile properties (Roos, Rice, Connelly, & Vandervoort, 1999).…”

Section: Intrinsic Contractile Propertiescontrasting

confidence: 99%

The effects of long‐term muscle disuse on neuromuscular function in unilateral transtibial amputees

Sibley

Strike

Moudy

et al. 2020

Experimental Physiology

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New Findings What is the central question of this study?The effects of long‐term muscle disuse on neuromuscular function are unclear because disuse studies are typically short term. In this study, we used a new model (unilateral transtibial amputees) to investigate the effects of long‐term disuse on quadriceps neuromuscular function. What is the main finding and its importance?Kinetic analysis (knee‐extension moments during gait) indicated habitual disuse of the amputated limb quadriceps, accompanied by lower quadriceps muscle strength (60–76%) and neural activation (32–44%), slower contractile properties and altered muscle architecture in the amputated limb, which could not be predicted from short‐term disuse studies. Abstract The purpose of this study was to determine: (i) whether individuals with unilateral transtibial amputations (ITTAs), who habitually disuse the quadriceps muscles of their amputated limb, provide an effective model for assessing the effects of long‐term muscle disuse; and (ii) the effects of such disuse on quadriceps muscle strength and neuromuscular function in this population. Nine ITTAs and nine control subjects performed isometric voluntary knee extensions of both limbs to assess maximal voluntary torque (MVT) and the rate of torque development (RTD). The interpolated twitch technique and EMG normalized to maximal M‐wave were used to assess neural activation, involuntary (twitch and octet) contractions to assess intrinsic contractile properties, and ultrasound images of the vastus lateralis to assess muscle architecture. Clinical gait analysis was used to measure knee kinetic data during walking at an habitual speed. The ITTAs displayed 54–60% lower peak knee‐extensor moments during walking in the amputated compared with intact/control limbs, but the intact and control limbs were comparable for loading during walking and muscle strength variables, suggesting that the intact limb provides a suitable internal control for comparison with the disused amputated limb. The MVT and RTD were ∼60 and ∼75% lower, respectively, in the amputated than intact/control limbs. The differences in MVT appeared to be associated with ∼40 and ∼43% lower muscle thickness and neural activation, respectively, and the differences in RTD appeared to be associated with the decline in MVT coupled with slowing of the intrinsic contractile properties. These results indicate considerable changes in strength and neuromuscular function with long‐term disuse that could not be predicted from short‐term disuse studies.

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Section: Intrinsic Contractile Propertiescontrasting

confidence: 99%

The effects of long‐term muscle disuse on neuromuscular function in unilateral transtibial amputees

Sibley

Strike

Moudy

et al. 2020

Experimental Physiology

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“…In contrast, this slow-to-fast shift in fiber type is not found in the VL muscle from subjects with mild-to-moderate COPD (Doucet et al, 2004 ), while this transition does not seem to exist in upper peripheral muscles such as the deltoid muscle (Gea et al, 2001 ). Several factors have been proposed to explain the skeletal muscle dysfunction in COPD, such as muscle deconditioning and reduced physical activity, neuromuscular degeneration, systemic oxidative stress and inflammation, exacerbated catabolism, hormonal disturbance, smoking, nutritional status, pharmacological treatments, aging, or gas exchange abnormalities (Gea et al, 2013 ; Kapchinsky et al, 2018 ). However, it remains extremely difficult to identify which factor(s) is/are responsible for the alteration of fiber typing.…”

Section: Adaptation Of Skeletal Muscle Fiber Type Under Conditions Ofmentioning

confidence: 99%

Skeletal Muscle Fiber Type in Hypoxia: Adaptation to High-Altitude Exposure and Under Conditions of Pathological Hypoxia

Chaillou

2018

Front. Physiol.

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Skeletal muscle is able to modify its size, and its metabolic/contractile properties in response to a variety of stimuli, such as mechanical stress, neuronal activity, metabolic and hormonal influences, and environmental factors. A reduced oxygen availability, called hypoxia, has been proposed to induce metabolic adaptations and loss of mass in skeletal muscle. In addition, several evidences indicate that muscle fiber-type composition could be affected by hypoxia. The main purpose of this review is to explore the adaptation of skeletal muscle fiber-type composition to exposure to high altitude (ambient hypoxia) and under conditions of pathological hypoxia, including chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) and obstructive sleep apnea syndrome (OSAS). The muscle fiber-type composition of both adult animals and humans is not markedly altered during chronic exposure to high altitude. However, the fast-to-slow fiber-type transition observed in hind limb muscles during post-natal development is impaired in growing rats exposed to severe altitude. A slow-to-fast transition in fiber type is commonly found in lower limb muscles from patients with COPD and CHF, whereas a transition toward a slower fiber-type profile is often found in the diaphragm muscle in these two pathologies. A slow-to-fast transformation in fiber type is generally observed in the upper airway muscles in rodent models of OSAS. The factors potentially responsible for the adaptation of fiber type under these hypoxic conditions are also discussed in this review. The impaired locomotor activity most likely explains the changes in fiber type composition in growing rats exposed to severe altitude. Furthermore, chronic inactivity and muscle deconditioning could result in the slow-to-fast fiber-type conversion in lower limb muscles during COPD and CHF, while the factors responsible for the adaptation of muscle fiber type during OSAS remain hypothetical. Finally, the role played by cellular hypoxia, hypoxia-inducible factor-1 alpha (HIF-1α), and other molecular regulators in the adaptation of muscle fiber-type composition is described in response to high altitude exposure and conditions of pathological hypoxia.

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“…C-terminal agrin fragment-22 (CAF22) is a smaller fragment of CAFs and its circulating levels are associated with the NMJ degeneration and muscle defect in sarcopenia [ 13 ] and other catabolic conditions due to heart failure and stroke [ 14 , 15 ]. However, the association of plasma CAF22 with muscle wasting in the respiratory diseases is not well recognized despite the evidence that smoking and other conditions of lung injury can result in the destabilization of NMJs [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating Biomarkers of Accelerated Sarcopenia in Respiratory Diseases

Qaisar

Karim

Muhammad

et al. 2020

Biology

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Skeletal muscle dysfunction is a critical finding in many respiratory diseases. However, a definitive biomarker to assess muscle decline in respiratory diseases is not known. We analyzed the association of plasma levels of glycoprotein Dickkopf-3 (Dkk-3), c-terminal agrin fragment-22 (CAF22) and microRNAs miR-21, miR-134a, miR-133 and miR-206 with hand-grip strength (HGS) and appendicular skeletal mass index (ASMI) in male, 54–73-year-old patients with chronic obstructive pulmonary diseases (COPD), asthma or pulmonary TB (n = 83–101/group). Patients with respiratory diseases showed a reduction in HGS and gait speed, while a reduction in ASMI was only found in patients with pulmonary TB. Among the sarcopenia indexes, HGS showed the strongest correlation with plasma CAF22, miR-21 and miR-206 levels while ASMI showed the strongest correlation with Dkk-3 and miR-133 in respiratory diseases. We found a modest-to-significant increase in the plasma markers of inflammation, oxidative stress and muscle damage, which had varying degrees of correlations with Dkk-3, CAF22 and selected micro RNAs (miRs) in respiratory diseases. Taken together, our data show that plasma levels of Dkk-3, CAF22 and selected miRs can be useful tools to assess accelerated sarcopenia phenotype in the elderly with respiratory diseases.

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Smoke‐induced neuromuscular junction degeneration precedes the fibre type shift and atrophy in chronic obstructive pulmonary disease

Cited by 38 publications

References 82 publications

The effects of long‐term muscle disuse on neuromuscular function in unilateral transtibial amputees

The effects of long‐term muscle disuse on neuromuscular function in unilateral transtibial amputees

Skeletal Muscle Fiber Type in Hypoxia: Adaptation to High-Altitude Exposure and Under Conditions of Pathological Hypoxia

Circulating Biomarkers of Accelerated Sarcopenia in Respiratory Diseases

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