title: Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission.
abstract: The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5-20 day) spaceflights. The mice drawer system (MDS) program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days) exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1) into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL) muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca(2+)-activated K(+) channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures.
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Dorianna
authors.initials: D
authors.lastname: Sandonà
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Desaphy
authors.forename: Giulia M
authors.initials: GM
authors.lastname: Camerino
authors.forename: Elisa
authors.initials: E
authors.lastname: Bianchini
authors.forename: Stefano
authors.initials: S
authors.lastname: Ciciliot
authors.forename: Daniela
authors.initials: D
authors.lastname: Danieli-Betto
authors.forename: Gabriella
authors.initials: G
authors.lastname: Dobrowolny
authors.forename: Sandra
authors.initials: S
authors.lastname: Furlan
authors.forename: Elena
authors.initials: E
authors.lastname: Germinario
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Goto
authors.forename: Martina
authors.initials: M
authors.lastname: Gutsmann
authors.forename: Fuminori
authors.initials: F
authors.lastname: Kawano
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakai
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohira
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ohno
authors.forename: Anne
authors.initials: A
authors.lastname: Picard
authors.forename: Michele
authors.initials: M
authors.lastname: Salanova
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schiffl
authors.forename: Dieter
authors.initials: D
authors.lastname: Blottner
authors.forename: Antonio
authors.initials: A
authors.lastname: Musarò
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ohira
authors.forename: Romeo
authors.initials: R
authors.lastname: Betto
authors.forename: Diana
authors.initials: D
authors.lastname: Conte
authors.forename: Stefano
authors.initials: S
authors.lastname: Schiaffino
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D015536:Down-Regulation; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D051381:Rats; D013026:Space Flight; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D015854:Up-Regulation; D014893:Weightlessness
chemical_list: D015850:Interleukin-6; D024681:Potassium Channels, Calcium-Activated; D007334:Insulin-Like Growth Factor I; D052248:Nitric Oxide Synthase Type I; D044767:Ubiquitin-Protein Ligases; D018995:Myosin Heavy Chains