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Introduction: Long-term confinement is known to be a stressful experience with multiple psycho-physiological effects. In the MARS500 project, a real-time simulation of a space-flight to Mars conducted in a hermetically isolated habitat, effects of long-term confinement could be investigated in a unique manner. The aim of this study was to evaluate effects of long-term-confinement on brain cytoarchitecture., Material & Methods: The participants of the MARS500 project underwent 3T-MR imaging including a dedicated DTI-sequence before the isolation, right after ending of confinement and 6 months after the experiment. Voxelwise statistical analysis of the DTI data was carried out using tract-based-spatial statistics, comparing an age-matched control group., Results: At all three sessions, significant lower fractional anisotropy (FA) than in controls was found in the anterior parts of the callosal body of the participants. Furthermore, after ending of confinement a wide-spread FA reduction could be seen in the right hemisphere culminating in the temporo-parietal-junction-zone. All these areas with decreased FA predominantly showed an elevated radial diffusivity and mean diffusivity while axial diffusivity was less correlated., Discussion: Long-term confinement does have measurable effects on the microstructure of the brain white matter. We assume effects of sensory deprivation to account for the regional FA reductions seen in the right TPJ. The differences in the Corpus callosum were interpreted as due to preliminary conditions, e.g. personality traits or training effects. FA and radial diffusivity were the predominant DTI parameters with significant changes, suggesting underlying processes of myelin plasticity., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019. Published by Elsevier Ltd.)

Gravitational stress in general and microgravity (µg) in particular are regarded as major stress factors responsible for immune system dysfunction in space. To assess the effects of alternating µg and hypergravity (hyper-g) on immune cells, the attachment of peripheral blood mononuclear cells (PBMCs) to adhesion molecules under flow conditions and the antigen-induced immune activation in whole blood were investigated in parabolic flight (PF). In contrast to hyper-g (1.8 g) and control conditions (1 g), flow and rolling speed of PBMCs were moderately accelerated during µg-periods which were accompanied by a clear reduction in rolling rate. Whole blood analyses revealed a "primed" state of monocytes after PF with potentiated antigen-induced pro-inflammatory cytokine responses. At the same time, concentrations of anti-inflammatory cytokines were increased and monocytes displayed a surface molecule pattern that indicated immunosuppression. The results suggest an immunologic counterbalance to avoid disproportionate immune responses. Understanding the interrelation of immune system impairing and enhancing effects under different gravitational conditions may support the design of countermeasures to mitigate immune deficiencies in space.

During interplanetary exploration, chronic stress caused by long term isolation and confinement in the spacecraft is one of the major concerns of physical and psychological health of space travelers. And for human on Earth, more and more people live in an isolated condition, which has become a common social problem in modern western society. Collective evidences have indicated prolonged chronic stress could bring big influence to human immune function, which may lead to a variety of health problems. However, to what extent long-term isolation can affect the immune system still remains largely unknow. A simulated 520-d Mars mission provided an extraordinary chance to study the effect of prolonged isolation. Six healthy males participated in this mission and their active neuroendocrine and immune conditions were studied with saliva and blood samples from all participants on chosen time points during the isolation period. As a typical neuroendocrine parameter, stress hormone cortisol was measured in the morning saliva samples. Immune phenotype changes were monitored through peripheral leukocyte phenotype analysis. Using an ex vivo viral infection simulation assay we assessed the immune response changes characterized by the ability to produce representative endogenous pro-inflammatory cytokines. The results of this study revealed elevated cortisol levels, increased lymphocyte amount and heightened immune responses, suggesting that prolonged isolation acting as chronic stressors are able to trigger leukocyte phenotype changes and poorly controlled immune responses., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The endocannabinoid system (ECS) plays an important role in the regulation of physiological functions,from stress and memory regulation to vegetative control and immunity. The ECS is considered a central and peripheral stress response system to emotional or physical challenges and acts through endocannabinoids (ECs), which bind to .their receptors inducing subsequent effecting mechanisms. In our studies, the ECS responses have been assessed through blood concentrations of the ECs anandamide and 2-arachidonoylglycerol. In parallel, saliva cortisol was determined and the degree of perceived stress was quantified by questionnaires. This report summarizes the reactivity of the ECS in humans subjected to brief periods of kinetic stress and weightlessness during parabolic flights and to prolonged stress exposure during life onboard the International Space Station (ISS). Both conditions resulted in a significant increase in circulating ECs. Under the acute stress during parabolic flights, individuals who showed no evidence of motion sickness were in low-stress conditions and had a significant increase of plasma ECs. In contrast,highly stressed individuals with severe motion sickness had an absent EC response and a massive increase in hypothalamic-pituitary-adrenal axis activity. Likewise, chronic but well-tolerated exposure to weightlessness and emotional and environmental stressors on the ISS for 6 months resulted in a sustained increase in EC blood concentrations,which returned to baseline values after the cosmonauts'return. These preliminary results suggest that complex environmental stressors result in an increase of circulating ECs and that enhanced EC signaling is probably required for adaptation and tolerance under stressful conditions.