Interest in space habitation has grown dramatically with planning underway for the first human transit to Mars. Despite a robust history of domestic and international spaceflight research, understanding behavioral adaptation to the space environment for extended durations is scant. Here we report the first detailed behavioral analysis of mice flown in the NASA Rodent Habitat on the International Space Station (ISS). Following 4-day transit from Earth to ISS, video images were acquired on orbit from 16- and 32-week-old female mice. Spaceflown mice engaged in a full range of species-typical behaviors. Physical activity was greater in younger flight mice as compared to identically-housed ground controls, and followed the circadian cycle. Within 9–11 days after launch, younger (but not older), mice began to exhibit distinctive circling or ‘race-tracking’ behavior that evolved into a coordinated group activity. Organized group circling behavior unique to spaceflight may represent stereotyped motor behavior, rewarding effects of physical exercise, or vestibular sensation produced via self-motion. Affording mice the opportunity to grab and run in the RH resembles physical activities that the crew participate in routinely. Our approach yields a useful analog for better understanding human responses to spaceflight, providing the opportunity to assess how physical movement influences responses to microgravity.
Pregnant rats were flown on the NASA Space Shuttle during the early developmental period of their fetuses' vestibular apparatus and onset of vestibular function. The authors report that prenatal spaceflight exposure shapes vestibular-mediated behavior and central morphology. Postflight testing revealed (a) delayed onset of body righting responses, (b) cardiac deceleration (bradycardia) to 70°h ead-up roll, (c) decreased branching of gravistatic afferent axons, but (d) no change in branching of angular acceleration receptor projections with comparable synaptogenesis of the medial vestibular nucleus in flight relative to control fetuses. Kinematic analyses of the dams' on-orbit behavior suggest that, although the fetal otolith organs are unloaded in microgravity, the fetus' semicircular canals receive high levels of stimulation during longitudinal rotations of the mother's weightless body. Behaviorally derived stimulation from maternal movements may be a significant factor in studies of vestibular sensory development. Taken together, these studies provide evidence that gravity and angular acceleration shape prenatal organization and function within the mammalian vestibular system. Keywords microgravity; development; fetus; maternal; otoliths Sensory deprivation during ontogenesis has proven to be a highly effective tool for investigating sensory development. Studies employing dark-rearing (Hubel & Wiesel, 1982), plugging the ears (Batkin, Groth, Watson, & Ansberry, 1970), obstructing the nares (Kucharsky & Hall, 1987), or eliminating tactile input normally supplied by the vibrissae (Woolsey & Wann, 1976) have yielded important insights into how stimulation plays an active, formative role during sensory ontogenesis. Sensory deprivation during early life produces enduring deficits in sensory functions. For example, clinical observations (Peters, Litovsky, Parkinson, & Lake, 2007;Rubinstein & Miller, 1999) have shown that proper acoustic input is critical for the development of hearing; delayed provision of a cochlear implant in children can prevent acquisition of proper understanding of spoken words. Similarly, understanding the roles of early stimulation has augmented clinical approaches in the treatment of visual impairments (Maurer, Lewis, Brent, & Levin, 1999). In contrast to other sensory systems, our understanding of neurovestibular ontogeny has progressed slowly, due, in part, to the historic difficulty of depriving young organisms of the Earth-constant stimulus of gravity. A growing number of techniques are proving their utility for depriving the immature mammalian vestibular system of sensory input. For example, the semicircular canals (Geisler & Gramsbergen, 1998; Correspondence concerning this article should be addressed to April E. Ronca, Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC 27157. E-mail: aronca@wfubmc.edu. Relatively little work has focused on the emergence of vestibular function. Yet within the sequentially fixed, highly conserve...
The hindlimb unloading (HU) model has been used extensively to simulate the cephalad fluid shift and musculoskeletal disuse observed in spaceflight with its application expanding to study immune, cardiovascular and central nervous system responses, among others. Most HU studies are performed with singly housed animals, although social isolation also can substantially impact behavior and physiology, and therefore may confound HU experimental results. Other HU variants that allow for paired housing have been developed although no systematic assessment has been made to understand the effects of social isolation on HU outcomes. Hence, we aimed to determine the contribution of social isolation to tissue responses to HU. To accomplish this, we developed a refinement to the traditional NASA Ames single housing HU system to accommodate social housing in pairs, retaining desirable features of the original design. We conducted a 30-day HU experiment with adult, female mice that were either singly or socially housed. HU animals in both single and social housing displayed expected musculoskeletal deficits versus housing matched, normally loaded (NL) controls. However, select immune and hypothalamic-pituitary-adrenal (HPA) axis responses were differentially impacted by the HU social environment relative to matched NL controls. HU led to a reduction in % CD4+ T cells in singly housed, but not in socially housed mice. Unexpectedly, HU increased adrenal gland mass in socially housed but not singly housed mice, while social isolation increased adrenal gland mass in NL controls. HU also led to elevated plasma corticosterone levels at day 30 in both singly and socially housed mice. Thus, musculoskeletal responses to simulated weightlessness are similar regardless of social environment with a few differences in adrenal and immune responses. Our findings show that combined stressors can mask, not only exacerbate, select responses to HU. These findings further expand the utility of the HU model for studying possible combined effects of spaceflight stressors.
Animal models are useful for exploring the health consequences of prolonged spaceflight. Capabilities were developed to perform experiments in low earth orbit with on-board sample recovery, thereby avoiding complications caused by return to Earth. For NASA's Rodent Research-1 mission, female mice (ten 32 wk C57BL/6NTac; ten 16 wk C57BL/6J) were launched on an unmanned vehicle, then resided on the International Space Station for 21/22d or 37d in microgravity. Mice were euthanized on-orbit, livers and spleens dissected, and remaining tissues frozen in situ for later analyses. Mice appeared healthy by daily video health checks and body, adrenal, and spleen weights of 37d-flight (FLT) mice did not differ from ground controls housed in flight hardware (GC), while thymus weights were 35% greater in FLT than GC. Mice exposed to 37d of spaceflight displayed elevated liver mass (33%) and select enzyme activities compared to GC, whereas 21/22d-FLT mice did not. FLT mice appeared more physically active than respective Gc while soleus muscle showed expected atrophy. RnA and enzyme activity levels in tissues recovered on-orbit were of acceptable quality. thus, this system establishes a new capability for conducting long-duration experiments in space, enables sample recovery on-orbit, and avoids triggering standard indices of chronic stress.
Using videographic analyses, we identified and quantified maternal contributions to the sensory environment of the perinatal rat (Rattus norvegicus) by analyzing, from the offspring's perspective, the dam's activities during gestation, labor, and delivery. Our observations indicate that pregnant females remain highly active during the final week of gestation, as compared with nonpregnant control animals. Exploratory movements, feeding, drinking, self-grooming, and other activities of the rat dam pitch, turn, accelerate, and expose fetuses to mechanical pressures. During parturition uterine contractions and maternal licking and handling provide vigorous tactile and vestibular stimuli to pups. Newly born pups are exposed to intense thermal stimulation, cooling rapidly to the temperature of the postnatal environment. Our results suggest that fetal and newborn rats are exposed during development to a broad range of maternally produced stimuli.
In this report, sex/gender research relevant to reproduction on Earth, in conjunction with the extant human and animal observations in space, was used to identify knowledge gaps and prioritize recommendations for future sex- and gender-specific surveillance and monitoring of male and female astronauts. With overall increased durations of contemporary space missions, a deeper understanding of sex/gender effects on reproduction-related responses and adaptations to the space environment is warranted to minimize risks and insure healthy aging of the men and women who travel into space.
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