Involvement of adenosine A1 receptor in the sleep-promoting effect of AR-001
- 주제(키워드) Adenosine , Adenosine A1 receptor , Sleep , small molecule compound , Insomnia
- 주제(DDC) 651.1
- 발행기관 아주대학교
- 지도교수 정이숙
- 발행년도 2023
- 학위수여년월 2023. 8
- 학위명 석사
- 학과 및 전공 일반대학원 바이오헬스규제과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000033116
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Insomnia is one of the most common sleep disorders, affecting 10-15% of the population. Classical remedies used to treat insomnia have various side effects. Therefore, new targets for the treatment of insomnia are attracting attention. This study investigated the beneficial effects and mechanisms of AR-001 on sleep. In a pentobarbital-induced sleep study, AR-001 improve sleep by decreased sleep onset latency and increased total sleep time, and the sleep-promoting effect of AR-001 was inhibited only by adenosine A1 receptor (A1R) antagonist administration, while unaffected by any other neurotransmitters agonists/antagonists. As a result of immunohistochemistry, AR-001 has been shown to increase the neural activity in the sleep-promoting region, ventrolateral preoptic nucleus (VLPO) and decrease the neural activity in the wake-promoting region, basal forebrain (BF) and lateral hypothalamus (LH), and these effects of AR-001 were significantly inhibited by A1R antagonist. In addition, AR-001 administration increased A1R mRNA levels in the mouse hypothalamus. In conclusion, the results of this study suggest that AR-001 can induce sleep-promoting effects through the A1R and may have therapeutic potential for insomnia.
more목차
Ⅰ. INTRODUCTION 1
A. Sleep 1
B. Sleep regulation 2
C. Insomnia 3
D. Aims of study 3
Ⅱ. MATERIALS AND METHODS 4
A. Materials 4
B. Animals 4
C. Pentobarbital-induced sleep test 5
D. c-Fos expression in Immunohistochemistry (IHC) 5
E. c-Fos expression in Immunofluorescence (IF) 6
F. Quantitative Real-Time PCR (qRT-PCR) 7
G. Western Blot Analysis 7
H. Statistical analysis 8
Ⅲ. RESULTS 9
A. The Sleep-promoting effect of AR-001 on pentobarbital-induced sleeping behaviors. 9
B. AR-001 mediates its sleep-promoting effect through the adenosine A1 receptor. 11
C. AR-001 modulate the neuronal activity of sleep-wake regulation region in the mice brain. 14
D. Effects of AR-001 on NF-κB p65 protein and adenosine A1 receptors mRNA levels. 21
E. Inhibition of the effect of AR-001 by NF-κB inhibitors. 23
IV. DISCUSSION 25
V. CONCLUSION 28
REFERENCES 29
