Abstract
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.
Highlights
Brain functions are modulated by various environmental factors including stress
In the present study, in order to elucidate the molecular bases for the effects of gravity changes on behavior, we investigated the effects of centrifugation-induced hypergravity on gene expression of brain-derived neurotrophic factor (BDNF) and 5-HTRs in various regions of the mouse brain
We investigated the effects of hypergravity (2g for 14 days) on the mRNA expression of BDNF and 5-HTRs with special reference to 5-HT1AR, 5-HT1BR and 5-HT2AR, because these receptors are involved in various physiological and pathological functions in the brain
Summary
Brain functions are modulated by various environmental factors including stress. The environmental factors entailed in spaceflight reportedly affect human physiological and psychological functions [1,2,3,4]. Understanding the effects of these environmental factors is important for biological research on adaptation to environmental changes and for maintaining the health conditions of crewmembers during spaceflight Among these factors, the effects of gravity changes on skeletal, muscular, cardiovascular, immune and vestibular systems have so far been extensively studied using humans and experimental animals. The effects of gravity changes on the nervous system are not fully understood, given the brain’s diverse structure and function Animal experiments under both spaceflight and ground-based conditions have revealed that hypergravity as well as microgravity modulate rodent brain function and behavior, including cognition and emotion [5,6,7,8,9,10]. Based on the previous studies reporting that BDNF and the 5-HT system are involved in various brain functions including anxiety, depression, aggression, learning and memory, and that dysregulations of these molecules are closely related to neuropsychiatric diseases [19,20,21,22,23], we hypothesized that these molecules are vulnerable to gravity changes and most likely mediate the effects of gravity changes on various types of behavior
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