Comparative Transcriptomics Identifies Neuronal and Metabolic Adaptations to Hypergravity and Microgravity in Caenorhabditis elegans

Abstract

Deep space exploration is firmly within reach, but health decline during extended spaceflight remains a key challenge. In this study, we performed comparative transcriptomic analysis of Caenorhabditis elegans responses to varying degrees of hypergravity and to two spaceflight experiments (ICE-FIRST and CERISE). We found that progressive hypergravitational load concomitantly increases the extent of differential gene regulation and that subtle changes in 1,000 genes are reproducibly observed during spaceflight-induced microgravity. Consequently, we deduce those genes that are concordantly regulated by altered gravity per se or that display inverted expression profiles during hypergravity versus microgravity. Through doing so, we identify several candidate targets with terrestrial roles in neuronal function and/or cellular metabolism, which are linked to regulation by daf-16/FOXO signaling. These data offer a strong foundation from which to expedite mechanistic understanding of spaceflight-induced maladaptation in higher organisms and, ultimately, promote future targeted therapeutic development.

Loss of physical contact in space alters the dopamine system in C. elegans

“…They have been found to demonstrate highly comparable molecular and physiological maladaptations to spaceflight that are parallel to those observed in people. For example, we have shown the nematode Caenorhabditis elegans grown in mG displays reduced muscle cytoskeletal proteins, mitochondrial metabolic enzymes (Higashibata et al, 2016), and DAF-2/insulin/IGF-1 signaling (Willis et al, 2020). This molecular profile translates to impaired muscular performance and body length (Higashibata et al, 2016), paralleling functional changes reported in astronauts (Fitts et al, 2010;Nicogossian et al, 2016).…”

Spaceflight affects neuronal morphology and alters transcellular degradation of neuronal debris in adult Caenorhabditis elegans

“…However, in space-flown animals, we observed a reversal in exopher-genesis rate between ALMR and ALML neurons. Although the reason underlying this reversal is unclear, a recent study of reproducible transcriptomic changes in space-flown C. elegans ( Willis et al., 2020 ) identified downregulated genes predicted to be under the control of the transcription factor NSY-7, which is involved in determination of neuronal left/right asymmetry ( Lesch et al., 2009 ). Together, these results suggest that spaceflight may influence the left/right asymmetries in the C. elegans nervous system and potentially affect side-specific neuronal functions.…”

Spaceflight Affects Neuronal Morphology and Alters Transcellular Degradation of Neuronal Debris in Adult <i>Caenorhabditis Elegans</i>

“…Although the reason underlying this reversal is unclear, a recent study of reproducible transcriptomic changes in space-flown C. elegans (Willis et al, 2020) identified downregulated genes predicted to be under the control of the transcription factor NSY-7, which is involved in determination of neuronal left/right asymmetry (Lesch et al, 2009). Together, these results suggest that spaceflight may influence the left/right asymmetries in the C. elegans nervous system and potentially affect side-specific neuronal functions.…”