수면 분절 유발 쥐의 해마조직에서 Inflammasome의 활성화 연구 = A study on inflammasome activation in rat hippocampus subjected to sleep fragmentation

다국어 초록 (Multilingual Abstract)

ABSTRACT

A study on inflammasome activation in rat hippocampus subjected to sleep fragmentation.

Hoon-Jung Jwa
Director: Chol Shin, MD, PhD
Korea University
Seoul, South Korea

Continuation of sleep is important for body health and cognitive function. Several experimental studies have been conducted to clarify the exact mechanisms underlying the effect of sleep fragmentation (SF) on cognitive functions, but it remains still unknown. It has been reported that up-regulation of Nod-like receptor 3 (NLRP3) inflammasome is associated with several kinds of chronic diseases such as diabetes and insulin resistance. In this study, I investigated whether SF affects the NLRP3 activation in rat hippocampus using a walking wheel system.
7-weeks old eight male Wistar rats were used for SF model validation. Four and eight day sleep fragmentation was accomplished by a forced walking wheel system with a wheel on/off cycle of 30-s on/90-s off to mimic the arousal that is common in patients with severe sleep apnea. Time interval of exercise control (EC) was set at 10 min on/30 min off. Then, forty-eight male Wistar rats were randomly divided into the 4-day SF group, 4-day EC group, 8-day SF group, and 8-day EC group. Western blot analysis revealed that SF induced up-regulation of NLRP3 inflammasome complex. In accordance with the expression level of the complex, malondialdehyde levels were more increased in the SF group than in the EC group. There were no significant changes in ATP levels between 4 and 8 day SF groups and corresponding EC groups, indicating that SF-induced activation of NLRP3 is independent of ATP levels. I found that SF induced activation of NLRP3 inflammasome in rat hippocampus. A further study is required to clarify the role of NLRP3 inflammasome in SF-associated cognitive impairments.

Keywords
Sleep fragmentation; Nod-like receptor 3; Inflammasome; Western blot; Malondialdehyde

목차 (Table of Contents)

• CONTENTS
• ABSTRACT ························i
• LIST OF FIGURES ························ ii
• LIST OF TABLES ························ iii
• I. INTRODUCTION ························ 1
• II. MATERIAL AND METHODS ························ 8
• 1. Animals ························8
• 2. Sleep surgery ························9
• 3. Conditions for sleep recording ························ 9
• 4. Acclimatization to device ························ 10
• 5. Sleep fragmentation and exercise control fragmentation protocol ························ 10
• 6. Sample collection························11
• 7. Western blot analysis ························ 11
• 8. ATP measurements ························12
• 9. Lipid peroxidation measurements ························13
• 10. Data and statistical analysis ························ 13
• III. RESULTS ························ 14
• 1. Model validation ························14
• 2. Western blot analysis························16
• 3. Results for ATP measurements ························ 19
• 4. Results for lipid peroxidation ························ 20
• IV. DISCUSSION ························ 22
• V. REFERENCES ························ 26