Mast cell involvement in glucose tolerance impairment caused by chronic mild stress with sleep disturbance

Sachiko Chikahisa,Seiji Nishino,Saki Harada,Hiroyoshi Séi,Noriyuki Shimizu,Airi Otsuka,Tetsuya Shiuchi

doi:10.1038/s41598-017-14162-w

Sachiko Chikahisa, Seiji Nishino + Show 5 more

Open Access

https://doi.org/10.1038/s41598-017-14162-w

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Abstract

We have developed a chronic mild stress (MS) mouse model by simply rearing mice on a wire net for 3 weeks and investigated the effects of MS on glucose homeostasis and sleep. MS mice showed impaired glucose tolerance and disturbed sleep. One-week treatment with a histamine H1 receptor antagonist (H1RA) ameliorated the glucose intolerance and improved sleep quality in MS mice. MS mice showed an increased number of mast cells in both adipose tissue and the brain. Inhibition of mast cell function ameliorated the impairment in both glucose tolerance and sleep. Together, these findings indicate that mast cells may represent an important pathophysiological mediator in sleep and energy homeostasis.

Highlights

We recently found that mast cells in the brain play a significant role in the regulation of sleep and fundamental neurobehaviour such as food-seeking behaviour[1]
The expression of corticotropin-releasing hormone (CRH) mRNA and protein in the hypothalamus and the adrenal gland weight of mild stress (MS) mice were increased, the plasma concentration of corticosterone was at a similar level to that of CNT (Fig. 2b,c)
This study shows that MS by rearing on a wire net impairs glucose and sleep homeostasis, which is accompanied by an increased population of mast cells in the white adipose tissue (WAT) and brain

Summary

Introduction

We recently found that mast cells in the brain play a significant role in the regulation of sleep and fundamental neurobehaviour such as food-seeking behaviour[1]. Mast cells are immune cells derived from bone marrow progenitors[2,3,4] These cells infiltrate most tissues, mature in local tissues depending on microenvironmental factors and produce and secrete numerous mediators including histamine[2,3]. We developed a chronic mild stress (MS) model that is useful in the evaluation of chronic hypnotic effects by placing mice on a wire net Using this model, we studied the effects of chronic environmental stress on energy metabolism and sleep homeostasis. Our results indicate that MS induced notable changes in glucose and sleep homeostasis with an increased number of mast cells in the brain and adipose tissue

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Conclusion