Circadian rhythm resynchronization improved isoflurane-induced cognitive dysfunction in aged mice

被引：46

作者：

Song, Jia ^{[1
]}

Chu, Shuaishuai ^{[1
]}

Cui, Yin ^{[1
]}

Qian, Yue ^{[1
]}

Li, Xiuxiu ^{[1
]}

Xu, Fangxia ^{[1
]}

Shao, Xueming ^{[1
]}

Ma, Zhengliang ^{[1
]}

Xia, Tianjiao ^{[1
,2
]}

Gu, Xiaoping ^{[1
]}

机构：

[1] Nanjing Univ, Affiliated Drum Tower Hosp, Med Dept, Dept Anesthesiol, 321 Zhong Shan Rd, Nanjing 210008, Jiangsu, Peoples R China

[2] Nanjing Univ, Jiangsu Key Lab Mol Med, Nanjing 210093, Jiangsu, Peoples R China

来源：

EXPERIMENTAL NEUROLOGY | 2018年 / 306卷

基金：

中国国家自然科学基金;

关键词：

isoflurane; cognition dysfunction; circadian rhythm; melatonin; RANDOMIZED-CONTROLLED-TRIAL; ALZHEIMERS-DISEASE; SUPRACHIASMATIC NUCLEUS; SLEEP QUALITY; MELATONIN; IMPAIRMENT; CLOCK; RATS; ANESTHESIA; SURGERY;

D O I：

10.1016/j.expneurol.2018.04.009

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Postoperative cognitive dysfunction (POCD) is a common clinical phenomenon characterized by cognitive deficits in patients after anesthesia and surgery. Advanced age is a significant independent risk factor for POCD. We previously reported that in young mice, sleep-wake rhythm is involved in the isoflurane-induced memory impairment. In present study, we sought to determine whether advanced age increased the risk of POCD through aggravated and prolonged post-anesthetic circadian disruption in the elderly. We constructed POCD model by submitting the mice to 5-h 1.3% isoflurane anesthesia from Zeitgeber Time (ZT) 14 to ZT19. Under novel object recognition assay (NOR) and Morris water maze (MWM) test, We found 5-h isoflurane anesthesia impaired the cognition of young mice for early 3 days after anesthesia but damaged the aged for at least 1 week. With Mini Mitter continuously monitoring, a 3.22 +/- 0.75 h gross motor activity acrophase delay was manifested in young mice on D1, while in the aged mice, the gross motor activity phase shift lasted for 3 days, consistent with the body temperature rhythm trends of change. Melatonin has been considered as an effective remedy for circadian rhythm shift. In aged mice, melatonin was pretreated intragastrically at the dose of 10 mg/kg daily for 7 consecutive days before anesthesia. We found that melatonin prevented isoflurane-induced cognitive impairments by restoring the locomotor activity and temperature circadian rhythm via clock gene resynchronization. Overall, these results indicated that Long-term isoflurane anesthesia induced more aggravated and prolonged memory deficits and circadian rhythms disruption in aged mice. Melatonin could prevent isoflurane-induced cognitive impairments by circadian rhythm resynchronization.

引用

页码：45 / 54

页数：10

共 42 条

[1] Melatonin ameliorates amyloid beta-induced memory deficits, tau hyperphosphorylation and neurodegeneration via PI3/Akt/GSk3 pathway in the mouse hippocampus [J].