Effect of orexin neuronal system to sepsis-associated encephalopathy and sleep disorder

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18285
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Hirosaki University
• Principal Investigator: Takekawa Daiki 弘前大学, 医学部附属病院, 助教 (80834803)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: オレキシン / 敗血症 / ラット / LPS

Outline of Final Research Achievements

We have previously reported that orexin nervous system has an anti-inflammatory effect in the central nervous system. In the present study, we investigated the relationship between sleep disorders in the rat model of mild systemic inflammation and sepsis caused by intraperitoneal administration of lipopolysaccharide, and orexin nervous system using transgenic rats with the characteristic that the orexin nervous system is shed with growth. Sleep disorders were stronger in the septic rat model than in the mild systemic inflammation rat model, but the REM sleep time in the septic model was shorter in the transgenic rat than in the wild-type rat. Although the survival rate of sepsis in transgenic rats is lower than that of wild-type rats, it was possible to show that sleep disorders may be involved in the mechanism.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果からオレキシン神経系がラット敗血症モデルや軽度全身炎症モデルの睡眠障害に影響を与えていることが示唆された。特に敗血症モデルではREM睡眠時間がオレキシン神経が脱落した遺伝子組み替えラットで有意に減少する睡眠障害が出現した。今後は外因性のオレキシン投与による睡眠障害の予防効果等の検討を追加し、オレキシン神経系をターゲットとした敗血症に伴う睡眠障害や敗血症関連脳症の治療法の確立を目指す。