In particular, we will try to summarize the experiments that, in our opinion, are more informative with regard to functional CNS changes that may derive from the exposure of mammalian brain to mission-relevant doses of HZE particles. We will then highlight established and more recent studies on the impact of ionizing radiations and/or space conditions on CNS structure and function, in humans and experimental models. In this review, we will briefly summarize the peculiar features of space radiation and the problems posed by its simulation. Nevertheless, recent reports have started to shed some light on this issue. Among them, the latter is particularly difficult to understand and predict. NASA has underscored four risks that may imply important health concerns for astronauts: acute radiation syndrome, carcinogenesis, degenerative tissue alterations, and central nervous system (CNS) loss of performance. However, our knowledge of the genetic and biological traits associated with sensitivity to space radiation is still very limited. In theory, these resources could allow for the screening of many crew candidates, to identify those possessing particularly sensitive or resistant biological backgrounds. Following recent developments in sequencing technologies, determination of individual genomes and acquisition of multi-omic information on individuals' biological samples has become a relatively low-cost routine. Individual sensitivity to acute or chronic exposure to radiation is dependent on genetic background. Without major technological leaps in shielding strategies, intrinsic or induced biological resilience to space radiation chronic exposure will probably be among the crucial factors to decide about risk acceptability. The observations from the ExoMars Trace Gas Orbiter indicate that a 6-month mission to Mars would imply a radiation dose equal to 60% of the limit which is commonly recommended for the full career of an astronaut. Therefore, it has been noted that “lack of knowledge about the biological effects of, and responses to, space radiation is the single most important factor limiting the prediction of radiation risk associated with human space exploration”. Efficient shielding of such radiation is very difficult, considering the mass constraints which spaceships need to respect. Among these factors, exposure to radiation dominated by particle shots and GCR of extremely high energy is of special concern. Genetically tractable animal models offer unique opportunities to directly investigate the genetic and molecular events that may affect the biological response to GCR and related radiation.Ĭompared to the terrestrial surface, space represents a hostile environment, characterized by the combination of microgravity, and a peculiar radiative environment, which could lead to severe health issues for astronaut crews engaged in long-term missions. A strong development of new knowledge and models, which may help to predict the risk of individual astronauts, is an absolute requirement in this field. The consequences of such damage to central nervous system health is a major concern. HZE are particularly damaging to biological tissues, because they can penetrate to much deeper layers of shielding materials than gamma rays and x-rays and produce within tissues long ionization tracks, with strongly clustered damage to information molecules. GCR consist of alpha particles, protons, and high atomic number ions, stripped of their electrons (HZE), which are relatively rare, but are also highly ionizing. In these missions, astronaut crew members will be exposed to moderate doses of the highly energetic particles that compose galactic cosmic rays (GCR). Space agencies are working to establish a permanent human presence on the moon and to reach Mars within the next few decades. 4Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche dell'Università della Campania “Luigi Vanvitelli”, Caserta, Italy.3Neuroscience Institute “Cavalieri Ottolenghi”, Orbassano, Italy.2Department of Neuroscience “Rita Levi Montalcini”, University of Torino, Turin, Italy.1Institute of Biosciences and Bioresources (IBBR), Consiglio Nazionale delle Ricerche (CNR), Naples, Italy. Giada Onorato 1,2,3,4 Elia Di Schiavi 1 * Ferdinando Di Cunto 2,3 *
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