Skeletal muscle fiber, nerve, and blood vessel breakdown in space‐flown rats

Abstract

Histochemical and ultrastructural analyses were performed postflight on hind limb skeletal muscles of rats orbited for 12.5 days aboard the unmanned Cosmos 1887 biosatellite and returned to Earth 2 days before sacrifice. The antigravity adductor longus (AL), soleus, and plantaris muscles atrophied more than the non-weight-bearing extensor digitorum longus, and slow muscle fibers were more atrophic than fast fibers. Muscle fiber segmental necrosis occurred selectively in the AL and soleus muscles; primarily, macrophages and neutrophils infiltrated and phagocytosed cellular debris. Granule-rich mast cells were diminished in flight AL muscles compared with controls, indicating the mast cell secretion contributed to interstitial tissue edema. Increased ubiquitination of disrupted myofibrils implicated ubiquitin in myofilament degradation. Mitochondrial content and succinic dehydrogenase activity were normal, except for subsarcolemmal decreases. Myofibrillar ATPase activity of flight AL muscle fibers shifted toward the fast type. Absence of capillaries and extravasation of red blood cells indicated failed microcirculation. Muscle fiber regeneration from activated satellite cells was detected. About 17% of the flight AL end plates exhibited total or partial denervation. Thus, skeletal muscle weakness associated with spaceflight can result from muscle fiber atrophy and segmental necrosis, partial motor denervation, and disruption of the microcirculation.

Macrophage deficiency in osteopetrotic (op/op) mice inhibits activation of satellite cells and prevents hypertrophy in single soleus fibers

“…Exposure to microgravity or hind limb unloading of rodents causes passive shortening of soleus muscle due to ankle plantarflexion (20,39,59), which reduces the mechanical stress (20) and neural activity (19,20,39,43). Even though it is well-reported that muscles composed predominantly of slowtwitch fibers are more susceptible to unloading-related atrophy (6,41,42,(45)(46)(47)59), atrophy in soleus muscle of mice composed of fast-twitch fibers mainly was also observed in all types of mice, as was reported elsewhere (40,48,55). The unloading-related decreases in fiber length and sarcomere number may be associated with the remodeling of muscle fibers and sarcomeres, as was reported before (20,59).…”

“…myonuclei; muscle fiber size; osteopetrotic mice; satellite cells; unloading and reloading SKELETAL MUSCLES ARE COMPOSED of multinucleated muscle fibers and have an extensive capacity for morphological and functional adaptation. For example, chronic unloading of muscles by bedrest in humans (45,46,64) and hind limb suspension and actual spaceflight in animals (6, 40 -42, 47, 59) result in muscle fiber atrophy and a shift toward a faster myosin heavy chain profile, particularly in antigravity muscles composed predominantly of slow-twitch fibers, such as the soleus (6,42,(45)(46)(47) and adductor longus (41, 59). Muscle fiber atrophy and the shift toward a faster myosin heavy chain profile are reversed in response to muscle reloading (41,45,46,59).…”

“…Muscle fiber atrophy and the shift toward a faster myosin heavy chain profile are reversed in response to muscle reloading (41,45,46,59). The muscular response to reloading appears to be closely related to intramuscular stimuli that are activated by mechanical loading (20,21,41,47,59) and/or muscle activation with reloading (1,12,20,22,41).Macrophage colony-stimulating factor (M-CSF, CSF-1) is a cytokine that influences hematopoietic stem cells to differentiate into macrophages and other cell types (54). Deficiency of macrophages has been well-reported in osteopetrotic (op/op) mutant mice with inactivating mutation of M-CSF gene, which results in the absence of certain macrophage and in osteopetrosis, following a lack of osteoclasts (60, 63).…”

Protein Import into Subsarcolemmal and Intermyofibrillar Skeletal Muscle Mitochondria

“…DISCUSSION Morphological, biochemical, and functional investigations of mitochondria have clearly established the existence of organellar heterogeneity in a variety of tissues, including brain (39), liver (40 -43), heart (44 -51), and skeletal muscle (19,(52)(53)(54). Studies of skeletal muscle subject to conditions of chronic use or disuse have indicated that SS mitochondria are synthesized or degraded in more dramatic fashion than IMF mitochondria (20,(55)(56)(57). This heterogeneous response of the two mitochondrial subfractions implies that a different pattern or regulation of mitochondrial biogenesis exists in distinct regions of the muscle cell, perhaps influenced by surrounding nuclear domains (58) or the proximity to environmental factors (e.g.. PO 2 ; Ref.…”

Efeitos cardiovasculares agudos da exposição ao ambiente microgravitacional

“…Partindo do princípio de que a complacência venosa esteja realmente aumentada 1,30 , a passagem para a postura ereta levaria imediatamente ao armazenamento de sangue nos membros inferiores, o que acentuaria a redução do retorno venoso causada pela hipovolemia. Este efeito poderia ainda ser amplificado por um aumento da permeabilidade capilar, conforme sugerido pela presença de petéquias hemorrágicas em astronautas do Skylab 1 e edema e extravasamento de hemácias de membros posteriores em ratos do projeto Cosmos 71 . No entanto, a avaliação indireta da resposta vascular ao estresse gravitacional mostrou resultados conflitantes: testes de head up tilt (o inverso de HDT) aplicados em astronautas do projeto Gemini logo após o regresso produziram aumentos de 12 a 82% no volume da panturrilha 1 ; por outro lado, astronautas recém-chegados das missões Apollo e de vôos de 6-9 dias no ônibus espacial apresentaram respectivamente diminuição ou ausência de alteração do volume da panturrilha quando submetidos ao teste de LBNP em posição supina 1,66 .…”