title: Combined Exposure to Simulated Microgravity and Acute or Chronic Radiation Reduces Neuronal Network Integrity and Survival.
abstract: During orbital or interplanetary space flights, astronauts are exposed to cosmic radiations and microgravity. However, most earth-based studies on the potential health risks of space conditions have investigated the effects of these two conditions separately. This study aimed at assessing the combined effect of radiation exposure and microgravity on neuronal morphology and survival in vitro. In particular, we investigated the effects of simulated microgravity after acute (X-rays) or during chronic (Californium-252) exposure to ionizing radiation using mouse mature neuron cultures. Acute exposure to low (0.1 Gy) doses of X-rays caused a delay in neurite outgrowth and a reduction in soma size, while only the high dose impaired neuronal survival. Of interest, the strongest effect on neuronal morphology and survival was evident in cells exposed to microgravity and in particular in cells exposed to both microgravity and radiation. Removal of neurons from simulated microgravity for a period of 24 h was not sufficient to recover neurite length, whereas the soma size showed a clear re-adaptation to normal ground conditions. Genome-wide gene expression analysis confirmed a modulation of genes involved in neurite extension, cell survival and synaptic communication, suggesting that these changes might be responsible for the observed morphological effects. In general, the observed synergistic changes in neuronal network integrity and cell survival induced by simulated space conditions might help to better evaluate the astronaut's health risks and underline the importance of investigating the central nervous system and long-term cognition during and after a space flight.
authors.affiliation: Radiobiology Unit, Laboratory of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre, SCK•CEN, Mol, Belgium.|Cell Systems and Imaging Research Group (CSI), Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.|Laboratory of Membrane Biochemistry and Applied Nutrition, Department of Pharmacology and Bio-molecular Sciences (DiSFeB), Università degli Studi di Milano, Milano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pani
authors.affiliation: Radiobiology Unit, Laboratory of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre, SCK•CEN, Mol, Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Verslegers
authors.affiliation: Radiobiology Unit, Laboratory of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre, SCK•CEN, Mol, Belgium.
authors.forename: Roel
authors.initials: R
authors.lastname: Quintens
authors.affiliation: Radiobiology Unit, Laboratory of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre, SCK•CEN, Mol, Belgium.
authors.forename: Nada
authors.initials: N
authors.lastname: Samari
authors.affiliation: Radiobiology Unit, Laboratory of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre, SCK•CEN, Mol, Belgium.
authors.forename: Louis
authors.initials: L
authors.lastname: de Saint-Georges
authors.affiliation: Cell Systems and Imaging Research Group (CSI), Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: van Oostveldt
authors.affiliation: Radiobiology Unit, Laboratory of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre, SCK•CEN, Mol, Belgium.|Cell Systems and Imaging Research Group (CSI), Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Baatout
authors.affiliation: Radiobiology Unit, Laboratory of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre, SCK•CEN, Mol, Belgium.
authors.forename: Mohammed Abderrafi
authors.initials: MA
authors.lastname: Benotmane
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D002142:Californium / Q000009:adverse effects; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D003359:Cosmic Radiation / Q000009:adverse effects; D007150:Immunohistochemistry; D051379:Mice; D016501:Neurites / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000166:cytology* / Q000528:radiation effects*; D011839:Radiation, Ionizing / Q000145:classification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014893:Weightlessness / Q000009:adverse effects*; D018474:Weightlessness Simulation; D014965:X-Rays / Q000009:adverse effects
chemical_list: D002142:Californium