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

Surabhi Sudevan,Kasumi Muto,Nahoko Higashitani,Toko Hashizume,Akira Higashibata,Rebecca A Ellwood,Colleen S Deane,Mizanur Rahman,Siva A Vanapalli,Timothy Etheridge,Nathaniel J Szewczyk,Atsushi Higashitani

doi:10.1016/j.isci.2022.103762

Abstract

SummaryProgressive neuromuscular decline in microgravity is a prominent health concern preventing interplanetary human habitation. We establish functional dopamine-mediated impairments as a consistent feature across multiple spaceflight exposures and during simulated microgravity in C. elegans. Animals grown continuously in these conditions display reduced movement and body length. Loss of mechanical contact stimuli in microgravity elicits decreased endogenous dopamine and comt-4 (catechol-O-methyl transferase) expression levels. The application of exogenous dopamine reverses the movement and body length defects caused by simulated microgravity. In addition, increased physical contact made comt-4 and dopamine levels rise. It also increased muscular cytoplasmic Ca2+ firing. In dop-3 (D2-like receptor) mutants, neither decrease in movement nor in body length were observed during simulated microgravity growth. These results strongly suggest that targeting the dopamine system through manipulation of the external environment (contact stimuli) prevents muscular changes and is a realistic and viable treatment strategy to promote safe human deep-space travel.

Highlights

Over almost 60 years, hundreds of humans have flown into space, spending up to one year living on the International Space Station (ISS)
Spaceflight and simulated mG result in decreased comt-4 expression and endogenous dopamine in C. elegans C. elegans grown under mG onboard the ISS over three separate ISS flight experiments consistently display decreased comt-4 gene expression, a catechol-O-methyltransferase DA degradation enzyme (Rodrıguez-Ramos et al, 2017), versus 1G centrifuge or ground control (Figures 1 and S1)
In the 2009 CERISE experiment to evaluate RNAi activity in space (Etheridge et al, 2011; Higashibata et al, 2016; Higashitani et al, 2009), comt-4 expression was reduced to approximately 30% in both 1st and 2nd generation N2 wild-type adults grown under microgravity compared to those grown in 1G centrifuge onboard ISS (Figure S1)

Summary

Introduction

Over almost 60 years, hundreds of humans have flown into space, spending up to one year living on the International Space Station (ISS). Loss of mechanical contact stimuli in microgravity elicits decreased endogenous dopamine and comt-4 (catechol-O-methyl transferase) expression levels.

Results

Conclusion