Vestibular-mediated increase in central serotonin plays an important role in hypergravity-induced hypophagia in rats

Abe, Chikara; Tanaka, Kunihiko; Iwata, Chuzo; Morita, Hironobu

doi:10.1152/japplphysiol.00515.2010

Cited by 32 publications

(43 citation statements)

References 32 publications

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“…We showed previously that hypergravity elevates 5-HT concentration in the cerebrospinal fluid, which is completely abolished by the vestibular lesion [34]. In addition, intensive interactions between 5-HT and BDNF in the brain were reported [35].…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown that hypergravity increases 5-HT concentration in rodent cerebrospinal fluid [34]. 5-HTRs are widely distributed in the brain, and animal experiments using gene-knockout techniques and pharmacological experiments using receptor agonists/antagonists have reported that multiple 5-HTRs such as 5-HT1AR, 5-HT1BR and 5-HT2AR are involved differentially in emotion and cognition [20,40–43].…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

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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“…A 3 g environment was induced by centrifugation, and the cages (30 cm × 18 cm × 14 cm) were set in a custom‐made gondola‐type rotating box with a 1.5 m arm (Shimadzu, Kyoto, Japan) for 4 weeks as described previously (Abe et al. ). To obtain 3 g environment, 41 rpm was applied.…”

Section: Methodsmentioning

confidence: 99%

The vestibular system is critical for the changes in muscle and bone induced by hypergravity in mice

et al. 2016

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Gravity changes concurrently affect muscle and bone as well as induce alterations in vestibular signals. However, the role of vestibular signals in the changes in muscle and bone induced by gravity changes remains unknown. We therefore investigated the effects of vestibular lesions (VL) on the changes in muscle and bone induced by 3 g hypergravity for 4 weeks in C57BL/6J mice. Quantitative computed tomography analysis revealed that hypergravity increased muscle mass surrounding the tibia and trabecular bone mineral content, adjusting for body weight in mice. Hypergravity did not affect cortical bone and fat masses surrounding the tibia. Vestibular lesions blunted the increases in muscle and bone masses induced by hypergravity. Histological analysis showed that hypergravity elevated the cross‐sectional area of myofiber in the soleus muscle. The mRNA levels of myogenic genes such as MyoD, Myf6, and myogenin in the soleus muscle were elevated in mice exposed to hypergravity. Vestibular lesions attenuated myofiber size and the mRNA levels of myogenic differentiation markers enhanced by hypergravity in the soleus muscle. Propranolol, a β‐blocker, antagonized the changes in muscle induced by hypergravity. In conclusion, this study is the first to demonstrate that gravity changes affect muscle and bone through vestibular signals and subsequent sympathetic outflow in mice.

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“…“Vestibular-mediated increase in central serotonin plays an important role in hyper gravity-induced hypophagia in rats” (Abe et al, 2010). …”

Section: Pump Advantages Anonymous (2011ab) Over Other Selected Methmentioning

confidence: 99%

Drug Delivery: Enabling Technology for Drug Discovery and Development. iPRECIO® Micro Infusion Pump: Programmable, Refillable, and Implantable

Tan¹,

Watts²,

Davis³

2011

Front. Pharmacol.

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Successful drug delivery using implantable pumps may be found in over 12,500 published articles. Their versatility in delivering continuous infusion, intermittent or complex infusion protocols acutely or chronically has made them ubiquitous in drug discovery and basic research. The recent availability of iPRECIO®, a programmable, refillable, and implantable infusion pump has made it possible to carry out quantitative pharmacology (PKPD) in single animals. When combined with specialized catheters, specific administration sites have been selected. When combined with radiotelemetry, the physiologic gold standard, more sensitive and powerful means of detecting drug induced therapeutic, and/or adverse effects has been possible. Numerous application examples are cited from iPRECIO® use in Japan, United States, and Europe with iPRECIO® as an enabling drug delivery device where the refillable and programmability functionality were key benefits. The ability to start/stop drug delivery and to have control periods prior dosing made it possible to have equivalent effects at a much lower dose than previously studied. Five different iPRECIO® applications are described in detail with references to the original work where the implantable, refillable, and programmable benefits are demonstrated with their different end-points.

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Vestibular-mediated increase in central serotonin plays an important role in hypergravity-induced hypophagia in rats

Cited by 32 publications

References 32 publications

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

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

The vestibular system is critical for the changes in muscle and bone induced by hypergravity in mice

Drug Delivery: Enabling Technology for Drug Discovery and Development. iPRECIO® Micro Infusion Pump: Programmable, Refillable, and Implantable

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