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PROtection MEdiated by Antioxidant NanoTEchnOlogy Against Neuronal Damage in Space (PROMETEO, Antioxidant Protection)

ABSTRACT: Oxidative stress (OS) is the mechanism at the base of many deleterious effects of spaceflight, involving exposure to microgravity (MG, also termed µg) and cosmic radiation (CR), and it is inherent to the genesis of several pathological conditions on Earth (among which Crohn’s and Parkinson’s diseases). Arising from the unbalanced production and elimination of pro-oxidant chemical species, OS implies short- and long-term alterations of targets from the molecular up to the whole organism level. The central nervous system (CNS) is the most critical target of OS, requiring special antioxidant protection with the increasing duration of spaceflights and in view of interplanetary travels. MG- and CR-induced cognitive and motor alterations, which are well known to progressively deteriorate human performance in space and can have life-threatening consequences on astronauts, can indeed be ascribed to dopamine dysregulation following OS generated during spaceflight This project proposes the use of polydopamine-based nanoparticles (NPs) to provide 1) antioxidant protection and 2) catecholaminergic support to neurons undergoing exposure to altered gravity and radiation. The focus is on neuronal cells involved in cognitive and motor functions both in space, where any behavioural impairments pose significant risks to manned expeditions, and on Earth, where dopaminergic neuron loss underlying Parkinson’s disease (PD) progression still requires effective contrast. This project in particular aims at exploring the connection between spaceflight and OS, by discriminating the effects of MG from those of CR, and at providing nanotechnology countermeasures to short- and potentially long-term alterations of the CNS due to spaceflight-induced reduction/oxidation (redox) reaction imbalance. This project also aspires at providing relevant evidence and therapeutic tools for the treatment of neurodegenerative conditions like PD on Earth.

ORGANISM(S): Homo sapiens

PROVIDER: GSE290701 | GEO | 2026/01/21

REPOSITORIES: GEO

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Project description:This study tested the hypothesis that transcription of immediate early genes is inhibited in T cells activated in microgravity (mg). Immunosuppression during spaceflight is a major barrier to safe long-term human space habitation and travel. The goals of these experiments were to prove that mg was the cause of impaired T cell activation during spaceflight as well as understand the mechanisms controlling early T cell activation. T cells from 4 human donors were stimulated with concanavalin A (ConA) and anti-CD28 onboard the International Space Station (ISS). An onboard centrifuge was used to generate a 1g simultaneous control to isolate the effects of mg from other variables of spaceflight. Microarray expression analysis after 1.5 hours of activation demonstrated that mg- and 1g-activated T cells had distinct patterns of global gene expression and identified 47 genes that were significantly differentially down-regulated in mg. Importantly, several key immediate early genes were inhibited in mg. T cells were isolated from human volunteers. T cells from each donor were kept separate and loaded into individual chambers in separate cassettes for the following treatments: mg non-activated, mg activated, and 1g activated. Therefore, samples represent biological triplicates. Experimental units were launched into space and placed into the KUBIK facility onboard the International Space Station. The 1g units were placed in the central centrifuge positions and centrifuged with an applied 1g force. The mg units were place in the static positions for continued mg exposure. After 30 minutes of pre-incubation, mg non-activated units were fixed by addition of RNALater (QIAGEN, Valencia, CA), removed from the incubator, and stored in 4M-BM-0C. The mg and 1g activated units were injected with final concentration 10mg/ml Con A and 4mg/ml anti-CD28. These cassettes were replaced into KUBIK on either the centrifuge or static positions and activated for 1.5 hours. Activation was stopped with the addition of RNALater and the units were then moved to 4M-BM-0C storage. All units were returned to Earth for analysis.

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PROtection MEdiated by Antioxidant NanoTEchnOlogy Against Neuronal Damage in Space (PROMETEO, Antioxidant Protection)

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