Bioinformatic Study of Transcriptome Changes in the Mice Lumbar Spinal Cord After the 30-Day Spaceflight and Subsequent 7-Day Readaptation on Earth: New Insights Into Molecular Mechanisms of the Hypogravity Motor Syndrome

Abstract

The hypogravity motor syndrome (HMS) is one of the deleterious impacts of weightlessness on the human body in orbital space missions. There is a hypothesis that disorders of musculoskeletal system as part of HMS arise in consequence of changes in spinal motor neurons. The study was aimed at bioinformatic analysis of transcriptome changes in lumbar spinal cords of mice after a 30-day spaceflight aboard biosatellite Bion-M1 (space group, S) and subsequent 7-day readaptation to the Earth’s gravity (recovery group, R) when compared with control mice (C group) housed in simulated biosatellite conditions on the Earth. Gene ontology and human phenotype ontology databases were used to detect biological processes, molecular functions, cellular components, and human phenotypes associated with HMS. Our results suggest resemblance of molecular changes developing in space orbit and during the postflight recovery to terrestrial neuromuscular disorders. Remarkably, more prominent transcriptome changes were revealed in R vs. S and R vs. C comparisons that are possibly related to the 7-day recovery period in the Earth’s gravity condition. These data may assist with establishment of HMS pathogenesis and proposing effective preventive and therapeutic options.

Immunological and hematological outcomes following protracted low dose/low dose rate ionizing radiation and simulated microgravity

“…There are several consequences to living in low-Earth orbit. These include edema due to fluid and cardiovascular deconditioning 1 , myelin degeneration 2 , disorientation and motor control deficits 3 , 4 , visual deficits 5 , endocrine and hormonal alterations 6 , muscle tone wasting 7 , and bone loss due to lack of mechanical loading 8 . Upon return to Earth, there is a period of readaptation that includes acute motion sickness, unsteadiness, imbalance due to gravity-induced vestibular fluid shifts 9 , and blood pressure changes 10 – 12 .…”

Cytoskeleton Markers in the Spinal Cord and Mechanoreceptors of Thick-Toed Geckos after Prolonged Space Flights

“…After 30 days of space flight, in motor neurons of mice lumbar spinal cords, immunoexpression of the proteins responsible for synaptic transfer of a nervous impulse and proteins of heat shock proteins decreased [19]. In general, these results support the assumption that weightlessness affects the motor neurons of the spinal cord, which is a leading factor in HMS [8].…”

“…In the transcriptional profile analysis of the mice spinal cord after 30 days of space flight and readaptation, 178 genes, involved in 60 metabolic and signal pathways, with changed expression, were detected. A total of 118 genes of the increased expression and 60 of the decreased expression were revealed [8]. In the study of Islamov et al [23], cytoskeletal proteins were shown to participate in spinal cord alteration.…”

“…HMS is developed in conditions of cancellation or significant reduction of gravitational loads. It is characterised by the deep disturbances of the main proprioceptive activity-vestibular, muscular, supporting systems-including specific changes in skeletal muscles, particularly in the so-called postural muscles responsible for maintaining posture in the gravity field of the Earth [4][5][6][7][8] and alterations in functional and structural characteristics of the skeletal muscles-atony, atrophy, decreased strength contractions, and increased muscle fatigue [9]. Earlier, it has been shown that the important trigger of HMS is violation of sensory impulses from the skin [5].…”

“…Earlier, it has been shown that the important trigger of HMS is violation of sensory impulses from the skin [5]. For example, the absence of sensory stimuli from mechanoreceptors of the sole skin possibly results in the functional activity of motor neurons innervating leg muscles [8]. Neuro-and molecular-physiological study results suppose the supporting system afferentation acting as a trigger in tonic regulation system is a key factor in HMS [7,10].…”