Risk Neurogenes for Long-Term Spaceflight: Dopamine and Serotonin Brain System

Попова, Н. К.; Куликов, А. В.; Кондаурова, Е. М.; Цыбко, А. С.; Kulikova, Elizabeth A.; Краснов, И. Б.; Shenkman, Louis; Bazhenova, Ekaterina; Sinyakova, N. A.; Науменко, В. С.

doi:10.1007/s12035-014-8821-7

Cited by 41 publications

(28 citation statements)

References 44 publications

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“…These results suggest that DS can inhibit the abnormal changes in many neurotransmitters and therefore prevent SLSE-impaired learning and memory. Previous studies revealed that hippocampal NE levels, cortical 5-HT levels, and DA system activity were decreased in space or simulated microgravity (Blanc et al, 1998; Liu et al, 2010; Popova et al, 2015). We identified novel changes in neurotransmitters in simulated spaceflight that need to be further validated.…”

Section: Discussionmentioning

confidence: 99%

Dammarane Sapogenins Ameliorates Neurocognitive Functional Impairment Induced by Simulated Long-Duration Spaceflight

Dong

Liu

et al. 2017

Front. Pharmacol.

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Increasing evidence indicates the occurrence of cognitive impairment in astronauts under spaceflight compound conditions, but the underlying mechanisms and countermeasures need to be explored. In this study, we found that learning and memory abilities were significantly reduced in rats under a simulated long-duration spaceflight environment (SLSE), which includes microgravity, isolation confinement, noises, and altered circadian rhythms. Dammarane sapogenins (DS), alkaline hydrolyzed products of ginsenosides, can enhance cognition function by regulating brain neurotransmitter levels and inhibiting SLSE-induced neuronal injury. Bioinformatics combined with experimental verification identified that the PI3K-Akt-mTOR pathway was inhibited and the MAPK pathway was activated during SLSE-induced cognition dysfunction, whereas DS substantially ameliorated the changes in brain. These findings defined the characteristics of SLSE-induced cognitive decline and the mechanisms by which DS improves it. The results provide an effective candidate for improving cognitive function in spaceflight missions.

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Section: Discussionmentioning

confidence: 99%

Dammarane Sapogenins Ameliorates Neurocognitive Functional Impairment Induced by Simulated Long-Duration Spaceflight

Dong

Liu

et al. 2017

Front. Pharmacol.

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“…It was reported that one-month spaceflight did not change BDNF gene expression in the brain regions including the frontal cortex, visual cortex, caudate putamen, hippocampus, hypothalamus and midbrain raphe nuclei [16]. The effects on 5-HT1AR, 5-HT2AR and 5-HT3R were also examined in the same spaceflight, and it was reported that the spaceflight decreased 5-HT2AR gene expression in the hypothalamus without any significant effects on the expression of 5-HT1AR, 5-HT2AR and 5-HT3R in other brain regions [17]. These effects were different from those of the present study.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of brain-derived neurotrophic factor (BDNF) was not affected in the same condition [16]. Among monoaminergic systems, the expression of serotonin 2A receptor (5-HT2AR) and dopamine D1 receptor was reduced in the hypothalamus [17]. However, there are still limited studies on spaceflight and ground-based experiments that investigated gene expression of functional molecules in the brain under altered gravity.…”

Section: Introductionmentioning

confidence: 99%

Effects of gravity changes on gene expression of BDNF and serotonin receptors in the mouse brain

Ishikawa

Ogura

et al. 2017

PLoS ONE

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Spaceflight entails various stressful environmental factors including microgravity. The effects of gravity changes have been studied extensively on skeletal, muscular, cardiovascular, immune and vestibular systems, but those on the nervous system are not well studied. The alteration of gravity in ground-based animal experiments is one of the approaches taken to address this issue. Here we investigated the effects of centrifugation-induced gravity changes on gene expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors (5-HTRs) in the mouse brain. Exposure to 2g hypergravity for 14 days showed differential modulation of gene expression depending on regions of the brain. BDNF expression was decreased in the ventral hippocampus and hypothalamus, whereas increased in the cerebellum. 5-HT1BR expression was decreased in the cerebellum, whereas increased in the ventral hippocampus and caudate putamen. In contrast, hypergravity did not affect gene expression of 5-HT1AR, 5-HT2AR, 5-HT2CR, 5-HT4R and 5-HT7R. In addition to hypergravity, decelerating gravity change from 2g hypergravity to 1g normal gravity affected gene expression of BDNF, 5-HT1AR, 5-HT1BR, and 5-HT2AR in various regions of the brain. We also examined involvement of the vestibular organ in the effects of hypergravity. Surgical lesions of the inner ear’s vestibular organ removed the effects induced by hypergravity on gene expression, which suggests that the effects of hypergravity are mediated through the vestibular organ. In summary, we showed that gravity changes induced differential modulation of gene expression of BDNF and 5-HTRs (5-HT1AR, 5-HT1BR and 5-HT2AR) in some brain regions. The modulation of gene expression may constitute molecular bases that underlie behavioral alteration induced by gravity changes.

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“…Based on findings from earlier animal studies related to spaceflight, it is hypothesized to find changes in humans as well. 30,100 Earth-based studies have shown that changes in neurotransmitters have major implications for attention, 101 (long-term) memory, 102 arousal 103 and motor activity. 104 Determining neurotransmitter and hormonal imbalance in space travelers is therefore important to get fundamental insight into how the central neural system adapt to microgravity and in addition, to get insight into the relation between these alterations and behavioral processes.…”

Section: Implications For Countermeasures and Neuroimaging In Spaceflmentioning

confidence: 99%

Spaceflight-induced neuroplasticity in humans as measured by MRI: what do we know so far?

et al. 2017

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Space travel poses an enormous challenge on the human body; microgravity, ionizing radiation, absence of circadian rhythm, confinement and isolation are just some of the features associated with it. Obviously, all of the latter can have an impact on human physiology and even induce detrimental changes. Some organ systems have been studied thoroughly under space conditions, however, not much is known on the functional and morphological effects of spaceflight on the human central nervous system. Previous studies have already shown that central nervous system changes occur during and after spaceflight in the form of neurovestibular problems, alterations in cognitive function and sensory perception, cephalic fluid shifts and psychological disturbances. However, little is known about the underlying neural substrates. In this review, we discuss the current limited knowledge on neuroplastic changes in the human central nervous system associated with spaceflight (actual or simulated) as measured by magnetic resonance imaging-based techniques. Furthermore, we discuss these findings as well as their future perspectives, since this can encourage future research into this delicate and intriguing aspect of spaceflight. Currently, the literature suffers from heterogeneous experimental set-ups and therefore, the lack of comparability of findings among studies. However, the cerebellum, cortical sensorimotor and somatosensory areas and vestibular-related pathways seem to be involved across different studies, suggesting that these brain regions are most affected by (simulated) spaceflight. Extending this knowledge is crucial, especially with the eye on long-duration interplanetary missions (e.g. Mars) and space tourism.

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Risk Neurogenes for Long-Term Spaceflight: Dopamine and Serotonin Brain System

Cited by 41 publications

References 44 publications

Dammarane Sapogenins Ameliorates Neurocognitive Functional Impairment Induced by Simulated Long-Duration Spaceflight

Dammarane Sapogenins Ameliorates Neurocognitive Functional Impairment Induced by Simulated Long-Duration Spaceflight

Effects of gravity changes on gene expression of BDNF and serotonin receptors in the mouse brain

Spaceflight-induced neuroplasticity in humans as measured by MRI: what do we know so far?

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