It is a consensus in the international manned space field that factors such as microgravity during the space flight can cause anxiety, depression and other important brain function abnormalities in astronauts. However, the neural mechanism at the molecular level is still unclear. Due to the limitations of research conditions, studies of biological changes in the primate brain have been comparatively few. We took advantage of -6° head-down bed rest (HDBR), one of the most implemented space analogues on the ground, to investigate the effects of simulated weightlessness on non-human primate brain metabolites. The Rhesus Macaque monkeys in the experiment were divided into three groups: the control group, the 42-day simulated weightlessness group with HDBR, and the recovery group, which had 28 days of free activity in the home cage after the HDBR. Liquid chromatography-mass spectrometry (LC-MS) was used to perform metabolomics analysis on specific brain areas of the monkeys under three experimental conditions. Our results show that simulated weightlessness can cause neurotransmitter imbalances, the amino acid and energy metabolism disorders, and hormone disturbances. But these metabolomics changes are reversible after recovery. Our study suggests that long-term brain damage in space flight might be reversible at the metabolic level. This lays a technical foundation for ensuring brain health and enhancing the brain function in future space studies.

The consequences of short-term disuse are well known, but effective countermeasures remain elusive. This study investigated the effects of neuromuscular electrical stimulation (NMES) during 5 days of bed rest on retaining lower limb muscle mass and muscle function in healthy young and old participants. One leg received NMES of the quadriceps muscle (3 × 30min/day) (NMES), and the other served as a control (CON). Isometric quadriceps strength (MVC), rate of force development (RFD), lower limb lean mass, and muscle thickness were assessed pre-and post-intervention. Muscle thickness remained unaltered with NMES in young and increased in old following bed rest, while it decreased in CON legs. In old participants, mid-thigh lean mass (MTLM) was preserved with NMES while decreased in CON legs. In the young, only a tendency to change with bed rest was detected for MTLM. MVC and early-phase RFD decreased in young and old, irrespective of NMES. In contrast, late-phase RFD was retained in young participants with NMES, while it decreased in young CON legs, and in the old, irrespective of NMES. NMES during short-term bed rest preserved muscle thickness but not maximal muscle strength. While young and old adults demonstrated similar adaptive responses in preventing the loss of skeletal muscle thickness, RFD was retained in the young only.

Orthostatic hypertension, defined by an increase of systolic blood pressure (SBP) of ≥20 mmHg upon standing, harbors an increased cardiovascular risk. We pooled data from two rigorously conducted head-down tilt bedrest studies to test the hypothesis that cardiopulmonary deconditioning and hypovolemia predispose to orthostatic hypertension. With bedrest, peak VO2 decreased by 6 ± 4 mlO2/min/kg (p < 0.0001) and plasma volume by 367 ± 348 ml (p < 0.0001). Supine SBP increased from 127 ± 9 mmHg before to 133 ± 10 mmHg after bedrest (p < 0.0001). In participants with stable hemodynamics following head-up tilt, the incidence of orthostatic hypertension was 2 out of 67 participants before bedrest and 2 out of 57 after bedrest. We conclude that in most healthy persons, cardiovascular deconditioning and volume loss associated with long-term bedrest are not sufficient to cause orthostatic hypertension.

Introduction: Spaceflight is associated with severe muscular adaptations with substantial inter-individual variability. A Hill-type muscle model is a common method to replicate muscle physiology in musculoskeletal simulations, but little is known about how the underlying parameters should be adjusted to model adaptations to unloading. The aim of this study was to determine how Hill-type muscle model parameters should be adjusted to model disuse muscular adaptations. Methods: Isokinetic dynamometer data were taken from a bed rest campaign and used to perform tracking simulations at two knee extension angular velocities (30°·s-1 and 180°·s-1). The activation and contraction dynamics were solved using an optimal control approach and direct collocation method. A Monte Carlo sampling technique was used to perturb muscle model parameters within physiological boundaries to create a range of theoretical and feasible parameters to model muscle adaptations. Results: Optimal fibre length could not be shortened by more than 67% and 61% for the knee flexors and non-knee muscles, respectively. Discussion: The Hill-type muscle model successfully replicated muscular adaptations due to unloading, and recreated salient features of muscle behaviour associated with spaceflight, such as altered force-length behaviour. Future researchers should carefully adjust the optimal fibre lengths of their muscle-models when trying to model adaptations to unloading, particularly muscles that primarily operate on the ascending and descending limbs of the force-length relationship.

Floatation-REST (Reduced Environmental Stimulation Therapy) minimizes stimulation of the nervous system by immersing subjects in an environment without sound or light while they effortlessly float in thermoneutral water supersaturated with Epsom salt. Here we investigated the relationship between altered states of consciousness (ASC) and its association with the affective changes induced by Floatation-REST. Using a within-subject crossover design, 50 healthy subjects were randomized to 60 min of Floatation-REST or 60 min of Bed-REST (an active control condition that entailed lying supine on a warm waterbed in a dark and quiet room). Following Floatation-REST, subjects felt significantly more relaxed, less anxious, and less tired than after Bed-REST. Floatation-REST also induced significantly more pronounced ASC characterized by the dissolution of body boundaries and the distortion of subjective time. The loss of body boundaries mediated the loss of anxiety, revealing a novel mechanism by which Floatation-REST exerts its anxiolytic effect.

OBJECTIVE: Exercise training during the National Aeronautics and Space Administration 70-d bed rest study effectively counteracted the decline in aerobic capacity, muscle mass, strength, and endurance. We aimed to characterize the genomic response of the participants\' vastus lateralis on day 64 of bed rest with and without exercise countermeasures.
METHODS: Twenty-two healthy young males were randomized into three groups: 1) bed rest only ( n = 7), 2) bed rest + aerobic (6 d·wk -1 ) and resistance training (3 d·wk -1 ) on standard equipment ( n = 7), and 3) bed rest + aerobic and resistance training using a flywheel device ( n = 8). The vastus lateralis gene and microRNA microarrays were analyzed using GeneSpring GX 14.9.1 (Agilent Technologies, Palo Alto, CA).
RESULTS: Bed rest significantly altered the expression of 2113 annotated genes in at least one out of the three study groups (fold change (FC) > 1.2; P < 0.05). Interaction analysis revealed that exercise attenuated the bed rest effect of 511 annotated genes (FC = 1.2, P < 0.05). In the bed rest only group, a predominant downregulation of genes was observed, whereas in the two exercise groups, there was a notable attenuation or reversal of this effect, with no significant differences between the two exercise modalities. Enrichment analysis identified functional categories and gene pathways, many of them related to the mitochondria. In addition, bed rest significantly altered the expression of 35 microRNAs (FC > 1.2, P < 0.05) with no difference between the three groups. Twelve are known to regulate some of the mitochondrial-related genes that were altered following bed rest.
CONCLUSIONS: Mitochondrial gene expression was a significant component of the molecular response to long-term bed rest. Although exercise attenuated the FC in the downregulation of many genes, it did not completely counteract all the molecular consequences.

Bone calcium turnover is aggravated in pregnant women recommended to bed rest. In the present cross-sectional study, we aimed to clarify whether preterm neonates would benefit from calcium supplementation during pregnancy. Forty-two mothers (37.5 ± 6.7 years), recommended bed rest at home, and 42 preterm neonates (24-37 weeks gestational age) were enrolled. Neonates\' serum calcium was quantified at birth. Mothers\' calcium intake from foods and supplements during pregnancy was assessed. Serum 25-OH-D was measured in both mothers and neonates at birth. Results showed that mothers\' calcium intake from foods was significantly lower than the recommended daily reference value (p < 0.001), while total calcium intake including supplements was close to the calcium reference value of 1000 mg/day (p = 0.648). Neonates\' serum calcium concentration was significantly higher in mothers receiving calcium supplementation during pregnancy compared to mothers who did not (p < 0.001). A significant association between neonates\' serum calcium levels and mothers\' calcium supplementation was evident, even when adjusted to mothers\' age, pre-pregnancy BMI, gestational age, and neonates\' birth weight (beta = +0.460, p = 0.025). A statistically significant correlation between neonates\' and mothers\' serum 25-OH-D levels was found (r = 0.891, p < 0.001). In conclusion, calcium status in preterm neonates, born by bedridden women, could be enhanced after calcium supplementation during gestation.

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Bed rest and limb immobilization are models of muscle disuse associated with skeletal muscle atrophy and reduced strength. The purpose of this systematic review was to examine the impact of protein or amino acid provision before and/or during a period of muscle disuse on muscle atrophy (primary outcome), strength and muscle protein synthesis (secondary outcomes) following a disuse period. We performed a systematic review of Embase, MEDLINE, Web of Science, PubMed and Clinical Trials in December 2022. Eligible studies were randomized controlled trials that combined a dietary protein or amino acid intervention versus control during an experimental model of disuse (bed rest or unilateral limb immobilization) in healthy individuals aged ≥18 years. Nine articles from eight independent trials were identified and rated for risk of bias by two authors. A meta-analysis of muscle mass data revealed no effect (standardized mean difference: 0.2; 95% confidence interval: -0.18 to 0.57, P = 0.31) of protein/amino acid intervention in preventing disuse-induced muscle atrophy. Although the meta-analysis was not conducted on strength or muscle protein synthesis data, there was insufficient evidence in the reviewed articles to support the use of protein/amino acid provision in mitigating the disuse-induced decline in either outcome measurement. Additional high-quality studies, including the reporting of randomization procedures and blinding procedures and the provision of statistical analysis plans, might be required to determine whether protein or amino acid provision serves as an effective strategy to attenuate muscle atrophy during periods of disuse.

Weightlessness during spaceflight can harm various bodily systems, including bone density, muscle mass, strength and cognitive functions. Exercise appears to somewhat counteract these effects. A terrestrial model for this is head-down bedrest (HDBR), simulating gravity loss. This mirrors challenges faced by older adults in extended bedrest and space environments. The first Canadian study, backed by the Canadian Space Agency, Canadian Institutes of Health Research, and Canadian Frailty Network, aims to explore these issues. The study seeks to: (1) scrutinize the impact of 14-day HDBR on physiological, psychological and neurocognitive systems, and (2) assess the benefits of exercise during HDBR. Eight teams developed distinct protocols, harmonized in three videoconferences, at the McGill University Health Center. Over 26 days, 23 participants aged 55-65 underwent baseline measurements, 14 days of -6° HDBR, and 7 days of recovery. Half did prescribed exercise thrice daily combining resistance and endurance exercise for a total duration of 1 h. Assessments included demographics, cardiorespiratory fitness, bone health, body composition, quality of life, mental health, cognition, muscle health and biomarkers. This study has yielded some published outcomes, with more forthcoming. Findings will enrich our comprehension of HDBR effects, guiding future strategies for astronaut well-being and aiding bedrest-bound older adults. By outlining evidence-based interventions, this research supports both space travellers and those enduring prolonged bedrest.