Physiological consequences of space flight, including abnormal bone metabolism, space radiation injury, and circadian clock dysregulation: Implications of melatonin use and regulation as a countermeasure

Hirayama, Jun; Hattori, Atsuhiko; Takahashi, Akihisa; Furusawa, Yukihiro; Tabuchi, Yoshiaki; Shibata, Masahiro; Nagamatsu, Aiko; Yano, Sachiko; Maruyama, Yusuke; Matsubara, Hideaki; Sekiguchi, Toshio; Suzuki, Nobuo

doi:10.1111/jpi.12834

Cited by 16 publications

(19 citation statements)

References 235 publications

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“…8 ). It is known that fish scales possess vascular tissue, including blood vessels 31 , 32 . In addition, Calcitonin has been shown to cross the blood–brain barrier in rats 33 .…”

Section: Discussionmentioning

confidence: 99%

Kynurenine promotes Calcitonin secretion and reduces cortisol in the Japanese flounder Paralichthys olivaceus

Ikari

Furusawa

Tabuchi

et al. 2023

Sci Rep

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Deep ocean water (DOW) exerts positive effects on the growth of marine organisms, suggesting the presence of unknown component(s) that facilitate their aquaculture. We observed that DOW suppressed plasma cortisol (i.e., a stress marker) concentration in Japanese flounder (Paralichthys olivaceus) reared under high-density condition. RNA-sequencing analysis of flounder brains showed that when compared to surface seawater (SSW)-reared fish, DOW-reared fish had lower expression of hypothalamic (i.e., corticotropin-releasing hormone) and pituitary (i.e., proopiomelanocortin, including adrenocorticotropic hormone) hormone-encoding genes. Moreover, DOW-mediated regulation of gene expression was linked to decreased blood cortisol concentration in DOW-reared fish. Our results indicate that DOW activated osteoblasts in fish scales and facilitated the production of Calcitonin, a hypocalcemic hormone that acts as an analgesic. We then provide evidence that the Calcitonin produced is involved in the regulatory network of genes controlling cortisol secretion. In addition, the indole component kynurenine was identified as the component responsible for osteoblast activation in DOW. Furthermore, kynurenine increased plasma Calcitonin concentrations in flounders reared under high-density condition, while it decreased plasma cortisol concentration. Taken together, we propose that kynurenine in DOW exerts a cortisol-reducing effect in flounders by facilitating Calcitonin production by osteoblasts in the scales.

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“…8 ). It is known that fish scales possess vascular tissue, including blood vessels 31 , 32 . In addition, Calcitonin has been shown to cross the blood–brain barrier in rats 33 .…”

Section: Discussionmentioning

confidence: 99%

Kynurenine promotes Calcitonin secretion and reduces cortisol in the Japanese flounder Paralichthys olivaceus

Ikari

Furusawa

Tabuchi

et al. 2023

Sci Rep

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“…In this review, we first introduce the regulation of circadian (Cassone, 1998;Schomerus and Korf, 2005;Bilu and Kronfeld-Schor, 2013) or seasonal (Reiter et al, 1980;Bartness et al, 1993;Malpaux et al, 1999;Foá and Bertolucci, 2003;viviD and Bentley, 2018) rhythms by melatonin. In addition, we describe the remarkable functions of melatonin in bones (Suzuki and Hattori, 2002;Hirayama et al, 2023) and in glucose metabolism (Karamitri and Jockers, 2019;Watanabe et al, 2023). Moreover, melatonin is a ubiquitously distributed molecule and is found in bacteria (Manchester et al, 1995), unicellular organisms (Pöggeler et al, 1991), fungi (Hattori et al, 1995), and plants (Hattori et al, 1995;Kolar and Machackova, 2005), where it has been proven to be a potent free radical scavenger and broad-spectrum antioxidant (Tan et al, 2002;Reiter et al, 2014;Slominski et al, 2018).…”

Section: [Review]mentioning

confidence: 91%

“…Mammalian melatonin receptors (Mel1a and Mel1b) have been detected in the suprachiasmatic nuclei (SCN) of the hypothalamus, the pars tuberalis (PT) of the pituitary gland (Fig. 1), and addi-tional brain areas, such as the paraventricular nucleus, periventricular nucleus, supraoptic nucleus, and hippocampus, as well as in peripheral organs, such as retina, bone, pancreas, liver, kidneys, adrenal gland, intestine, stomach, heart, lungs, skin, testis, and ovary (Hardeland et al, 2011;Li et al, 2013;Kumar et al, 2015;Hirayama et al, 2023). The Mel1a subtype is present within the SCN of the hypothalamus, the PT of the pituitary gland, and retinas, while the Mel1b subtype is mainly expressed in the retinas (Sugden et al, 2004).…”

Section: Melatonin Receptorsmentioning

confidence: 99%

Receptor-Mediated and Receptor-Independent Actions of Melatonin in Vertebrates

Hattori,

Suzuki

2024

Zoological Science

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“…The response of humans to LEO is complex, with many systems being affected [ 97 , 98 , 99 , 100 ] and with a variety of parameters changing in LEO. Some physiological changes are influenced by combinations of factors ( Table 1 ).…”

Section: Responses Of Humans To Space Flight and Living In Leomentioning

confidence: 99%

“…All of the above factors indicate that countermeasures may need to be personalized for each astronaut [ 100 , 107 ], and, furthermore, perhaps not all individuals are genetically and epigenetically suited for space flight. Therefore, selection to minimize the negative impact of space flight in the future may be required, a selection process that would impact the countermeasures and disease risks of individuals.…”

Section: Responses Of Humans To Space Flight and Living In Leomentioning

confidence: 99%

Homo sapiens—A Species Not Designed for Space Flight: Health Risks in Low Earth Orbit and Beyond, Including Potential Risks When Traveling beyond the Geomagnetic Field of Earth

Hart

2023

Life

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Homo sapiens and their predecessors evolved in the context of the boundary conditions of Earth, including a 1 g gravity and a geomagnetic field (GMF). These variables, plus others, led to complex organisms that evolved under a defined set of conditions and define how humans will respond to space flight, a circumstance that could not have been anticipated by evolution. Over the past ~60 years, space flight and living in low Earth orbit (LEO) have revealed that astronauts are impacted to varying degrees by such new environments. In addition, it has been noted that astronauts are quite heterogeneous in their response patterns, indicating that such variation is either silent if one remained on Earth, or the heterogeneity unknowingly contributes to disease development during aging or in response to insults. With the planned mission to deep space, humans will now be exposed to further risks from radiation when traveling beyond the influence of the GMF, as well as other potential risks that are associated with the actual loss of the GMF on the astronauts, their microbiomes, and growing food sources. Experimental studies with model systems have revealed that hypogravity conditions can influence a variety biological and physiological systems, and thus the loss of the GMF may have unanticipated consequences to astronauts’ systems, such as those that are electrical in nature (i.e., the cardiovascular system and central neural systems). As astronauts have been shown to be heterogeneous in their responses to LEO, they may require personalized countermeasures, while others may not be good candidates for deep-space missions if effective countermeasures cannot be developed for long-duration missions. This review will discuss several of the physiological and neural systems that are affected and how the emerging variables may influence astronaut health and functioning.

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Physiological consequences of space flight, including abnormal bone metabolism, space radiation injury, and circadian clock dysregulation: Implications of melatonin use and regulation as a countermeasure

Cited by 16 publications

References 235 publications

Kynurenine promotes Calcitonin secretion and reduces cortisol in the Japanese flounder Paralichthys olivaceus

Kynurenine promotes Calcitonin secretion and reduces cortisol in the Japanese flounder Paralichthys olivaceus

Receptor-Mediated and Receptor-Independent Actions of Melatonin in Vertebrates

Homo sapiens—A Species Not Designed for Space Flight: Health Risks in Low Earth Orbit and Beyond, Including Potential Risks When Traveling beyond the Geomagnetic Field of Earth

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