Abstract
Microgravity as well as chronic muscle disuse are two causes of low back pain originated at least in part from paraspinal muscle deconditioning. At present no study investigated the complexity of the molecular changes in human or mouse paraspinal muscles exposed to microgravity. The aim of this study was to evaluate longissimus dorsi adaptation to microgravity at both morphological and global gene expression level. C57BL/N6 male mice were flown aboard the BION-M1 biosatellite for 30 days (BF) or housed in a replicate flight habitat on ground (BG). Myofiber cross sectional area and myosin heavy chain subtype patterns were respectively not or slightly altered in longissimus dorsi of BF mice. Global gene expression analysis identified 89 transcripts differentially regulated in longissimus dorsi of BF vs. BG mice. Microgravity-induced gene expression changes of lipocalin 2 (Lcn2), sestrin 1(Sesn1), phosphatidylinositol 3-kinase, regulatory subunit polypeptide 1 (p85 alpha) (Pik3r1), v-maf musculoaponeurotic fibrosarcoma oncogene family protein B (Mafb), protein kinase C delta (Prkcd), Muscle Atrophy F-box (MAFbx/Atrogin-1/Fbxo32), and Muscle RING Finger 1 (MuRF-1) were further validated by real time qPCR analysis. In conclusion, our study highlighted the regulation of transcripts mainly linked to insulin sensitivity and metabolism in longissimus dorsi following 30 days of microgravity exposure. The apparent absence of robust signs of back muscle atrophy in space-flown mice, despite the overexpression of Atrogin-1 and MuRF-1, opens new questions on the possible role of microgravity-sensitive genes in the regulation of peripheral insulin resistance following unloading and its consequences on paraspinal skeletal muscle physiology.
Highlights
Low back pain is a common concern for crew members in short or long term duration space flight
The present study provides for the first time the global gene expression profile of longissimus dorsi in mice exposed to microgravity, which is central in further understanding of the structural, molecular and metabolic mechanism regulating vertebrate paraspinal muscle adaptation to spaceflight
Mice were randomly divided in 3 groups: BION Flown (BF), mice to be flown aboard the BION-M1 biosatellite exposed for 30 days to microgravity, BION Ground (BG) mice housed for 30 days in the same biosatellite habitat on ground, and Flight Control (FC) mice housed in the animal facility during the duration of the spaceflight
Summary
Low back pain is a common concern for crew members in short or long term duration space flight. Back pain onset in the major part of the analyzed cases was reported during the first days of space flight (day 1–12; Wing et al, 1991). The pathophysiology of microgravity induced back pain has been previously investigated and it is likely to be discogenic and somatic. Microgravity abolishes the physiological loads of the spine with a consequent increase of body-length determined essentially by an intervertebral disk (IVD) swelling and an adaptation of the thoracic and lumbar spine curvature. The disk expansion can stimulate type IV mechanoreceptors contributing to lumbar back pain onset (Sayson and Hargens, 2008; Sayson et al, 2013)
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