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Axial Myopathy
Published in Maher Kurdi, Neuromuscular Pathology Made Easy, 2021
The most well-known diseases predominantly affecting axial muscles are selenoprotein deficiency due to SNP1 and lamin A/C gene mutations. Heterozygous mutations in the skeletal muscle (RYR-1) that encode Ryanodine receptor-1 have recently been recognized as a rare novel entity associated with predominant axial myopathy. It is a late-onset condition associated with bent spine syndrome, camptocormia, proximal weakness, and lordosis. Pathologically, it is characterized by myopathic features, scattered cores, desmin aggregation, and mitochondrial abnormalities (Figure 22.2).
Cellular Adaptations to High-Intensity and Sprint Interval Training
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Martin J. MacInnis, Lauren E. Skelly
While the earlier sections described the general process through which the stress of exercise is transduced into signals to promote mitochondrial biogenesis (Figure 11.3), other processes have been proposed. Firstly, Place et al. (83) demonstrated that a single session of SIT caused fragmentation of the ryanodine receptor 1 protein (RYR1) 24 hours post-exercise. The authors suggested that this fragmentation leads to elevated Ca2+ leak from the sarcoplasmic reticulum, signalling the activation of mitochondrial biogenesis. Additional experiments demonstrated that this response was reactive oxygen species (ROS)–dependent and that well-trained humans did not demonstrate RYR1 fragmentation following a bout of SIT, potentially due to a greater abundance of endogenous antioxidant proteins (83). This result was further supported by Schlittler et al. (94), who reported decreased fragmentation following 3 weeks of SIT. Another potential ROS-dependent mechanism for exercise training–induced mitochondrial biogenesis was described by Larsen et al. (63). The authors' findings suggested that ROS-induced inactivation of aconitase contributed to SIT-induced increases in mitochondrial content. Although these mechanisms are intriguing, as they potentially explain the potency of SIT for increasing the oxidative capacity of skeletal muscle, future studies should investigate whether these mechanisms are specific to SIT or have a more general role in regulating mitochondrial adaptations to exercise: Do HIIT and MICT increase mitochondrial content through these mechanisms?
Mitochondrial Oxidative Stress in Aging and Healthspan
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
The molecular physiology of aged mouse skeletal muscles demonstrate leaky calcium release channel ryanodine receptor 1 (RyR1) located on the sarcoplasmic reticulum (SR), in association with muscle atrophy, weakness, and reduced exercise tolerance. The mechanisms include oxidative modifications that destabilize the interaction between RyR1 and calstabin1, which lead to increased calcium leak.166 This calcium leak reduces SR calcium load and hence reduces calcium release in response to muscle activation, resulting in reduced force production. Increased calcium leak also increases mitochondrial calcium uptake. In young normal muscles, rapid increase in mitochondrial calcium uptake may enhance tricarboxylic acid (TCA) cycle and increase mitochondrial ATP production.167,168 However, under chronic stress increase in mitochondrial calcium can increase mitochondrial ROS production.167,169 Thus, the elevated calcium leak in aged skeletal muscle can initiate a vicious cycle of mitochondrial ROS amplification and further RyR1 calcium leak. The mCAT prevented this vicious cycle and stabilized the RyR1 and calstabin1 interaction.166,170,171 Aged mCAT skeletal muscles had improved specific force, increased calcium release amplitude, reduced calcium leak, and increased SR loading compared with age-matched wild-type skeletal muscles.
Ophthalmological Manifestations of Hereditary Myopathies
Published in Journal of Binocular Vision and Ocular Motility, 2022
Marta Saint-Gerons, Miguel Angel Rubio, Gemma Aznar, Ana Matheu
Centronuclear and myotubular myopathy are characterized by small myofibers with central nuclei and central areas without contractile filaments. The term myotubular myopathy refers only to the X-linked form of the condition (XLMTM), while the term centronuclear myopathy (CNM) is normally used to indicate the autosomal form. Most cases of CNM are inherited in autosomal dominant pattern and less frequently as an autosomal recessive condition.1 CNM is caused by mutations of several genes DNM2 (encodes for dynamin 2), BIN1 (encodes for amphiphysin 2), and RYR1 (encodes for skeletal muscle ryanodine receptor 1).9,10 The most frequent entity in this group is myotubular myopathy linked to the X chromosome, caused by MTM1 mutations in Xq28. It presents with severe hypotonia and weakness at birth or prenatally and can be fatal in childhood. Reduced eye movements and eyelid ptosis are common features.1 Autosomal hereditary centronuclear myopathies are less severe than XLMTM. Ophthalmoparesis with or without ptosis is common in patients with CNM of various genetic backgrounds (DNM2, MTM1, RYR1).1,7,11
Exertional rhabdomyolysis and causes of elevation of creatine kinase
Published in The Physician and Sportsmedicine, 2020
Henrik Constantin Bäcker, Morgan Busko, Fabian Götz Krause, Aristomenis Konstantinos Exadaktylos, Jolanta Klukowska-Roetzler, Moritz Caspar Deml
In analyzing rates of serious medical complications associated with exertional rhabdomyolysis, one patient had to be resuscitated who was otherwise healthy during a long-distance run. No comorbidities were found in the further examination. It remains unclear if the rhabdomyolysis was the cause or consequence of resuscitation as mentioned earlier as this patient likely suffered from an exertional heat stroke. In addition, the mechanic resuscitation and especially fluid resuscitation are known to develop edema of the limb and muscles, which can cause even compartment syndrome and therefore rhabdomyolysis [32]. Otherwise, the patients were relatively healthy without serious complications. However, only in the patient who had to be resuscitated, further examinations for metabolic myopathies or genetic mutations like ryanodine receptor 1 (RYR1) were performed which revealed negative. This mutation causes neuromuscular diseases ranging from congenital myopathies to malignant hyperthermia. The prevalence between genetic mutation (RYR1 and 2 CACNAIS) and malignant hyperthermia is estimated at 1 in 3000 cases; however, the true incidence remains unknown. Hereby, malignant hyperthermia causes hyperthermia, hypermetabolism and muscle breakdown which share triggers such as in exercises [33]. Especially heat and exercises trigger rhabdomyolysis without exertional myalgia and in rare occasion isolated exertional myalgia [34].
Motor performance is preserved in healthy aged adults following severe whole-body hyperthermia
Published in International Journal of Hyperthermia, 2019
Marius Brazaitis, Henrikas Paulauskas, Nerijus Eimantas, Laura Daniuseviciute, Gintautas Volungevicius, Albertas Skurvydas
It has been proposed that attenuated neural excitability associated with a weaker electrically induced torque development potentially contributes to a postural instability with advanced age [22]. Age-related loss of muscle mass and force, and slowing of contractile speed and rate of muscle relaxation, contributes to peripheral muscle effects, including slowing of sarcoplasmic reticulum (SR) ATPase activity and utilization [26], slowed Ca2+ release and uptake rate from the SR [27], delayed or slower cross-bridge formation, and detachment [28], and decreased actomyosin sensitivity to Ca2+ [29]. A molecular basis of contractile apparatus dysfunction occurring with age is increased levels of reactive oxygen species (ROS) in the aged muscle, which are associated with altered cellular Ca2+ handling. Hyperthermia in ryanodine receptor 1 (RyR1) produces a leak of Ca2+ from the SR, which promotes mitochondrial dysfunction and oxidative stress-mediated changes of the RyR1 [30], resulting in channels that can leak SR Ca2+, leading to reduced SR Ca2+ release, myofibrillar Ca2+ sensitivity, and overall loss of muscle function [31]. Leaky RyR1 contributes to age-related loss of muscle function [32]. However, it can be expected that in older individuals, mainly because of attenuated thermoregulation [2] and muscle function [28,29] more heat will be accumulated and stored in the heated locations and the body core, resulting greater metabolically induced mitochondrial ROS production [33], leading to reduced Ca2+ kinetics and overall loss of muscle function [30].