β-lapachone exerts hypnotic effects via adenosine A1 receptor in mice
- 주제(키워드) β-lapachone , hypnotic , insomnia , sleep , adenosine A1 receptor
- 발행기관 아주대학교 일반대학원
- 지도교수 정이숙
- 발행년도 2024
- 학위수여년월 2024. 8
- 학위명 석사
- 학과 및 전공 일반대학원 약학과
- 실제URI http://www.dcollection.net/handler/ajou/000000034173
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Sleep is one of the most essential physiological phenomena for maintaining health. Sleep disturbances, such as insomnia, are often accompanied by psychiatric or physical conditions such as impaired attention, anxiety, and stress. Medication used to treat insomnia have concerns about potential side effects with long-term use, so interest in the use of alternative medicine is increasing. In this study, we investigated the hypnotic effects of β-lapachone (β-Lap), a natural naphthoquinone compound, using pentobarbital-induced sleep test, immunohistochemistry, real-time PCR, and western blot in mice. Our results indicated that β-Lap exerts a significant hypnotic effect by showing a decrease in sleep onset latency and an increase in total sleep time in pentobarbital-induced sleep model. The results of c-Fos immunostaining showed that β-Lap decreased neuronal activity in the basal forebrain and lateral hypothalamus, which are wakefulness-promoting brain regions, while increasing in the ventrolateral preoptic nucleus, a sleep-promoting region; all these effects were significantly abolished by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A1 receptor (A1R) antagonist. Western blot analysis showed that β-Lap increased extracellular signal-regulated kinase phosphorylation and nuclear factor-kappa B translocation from the cytoplasm to the nucleus; these effects were inhibited by DPCPX. Additionally, β-Lap increased the mRNA levels of A1R. Taken together, these results suggest that β-Lap exerts hypnotic effects, potentially through A1R.
more목차
Ⅰ. INTRODUCTION 1
A. Sleep 1
B. Sleep-wake regulation 2
C. Insomnia 3
D. β-lapachone 4
E. Aims of study 4
Ⅱ. MATERIALS AND METHODS 5
A. Animals 5
B. Materials 5
C. Pentobarbital-induced sleep model 6
D. c-Fos Immunohistochemistry 7
E. c-Fos Immunofluorescence 8
F. Western blot analysis 9
G. Quantitative Real-Time PCR 10
H. Statistical analysis 10
Ⅲ. RESULTS 11
A. β-Lap potentiates pentobarbital-induced sleep in mice 11
B. A1R antagonists reverse the hypnotic effect of β-Lap 13
C. β-Lap modulates the neuronal activity of sleep-wake regulatory regions in mouse brain 16
D. The hypnotic effect of β-Lap is related to the ERK1/2 signaling molecule 20
E. The increase in mRNA levels of A1R by β-Lap is related to NF-κB translocation 22
IV. DISCUSSION 25
V. CONCLUSION 29
REFERENCES 30
