Characterization of sevoflurane effects on Per2 expression using ex vivo bioluminescence imaging of the suprachiasmatic nucleus in transgenic rats

Matsuo, Izumi; Iijima, Norio; Takumi, Ken; Higo, Shimpei; Aikawa, Satoko; Anzai, Megumi; Ishii, Hirotaka; Sakamoto, Atsuhiro; Ozawa, Hitoshi

doi:10.1016/j.neures.2015.11.010

Cited by 16 publications

(12 citation statements)

References 23 publications

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“…In the current study, we show that midazolam or inflammation, each reported to induce delirium in humans (44, 45), lead to a significant dysregulation of PER2 in the SCN and the hippocampus of mice. These findings are consistent with other reports of PER2 dysregulation in the mouse brain following single exposure to anesthetics (46) or LPS (47). Moreover, patients with severe inflammation exhibit lower PER2 and altered melatonin plasma levels (48).…”

Section: Discussionsupporting

confidence: 93%

The Period 2 Enhancer Nobiletin as Novel Therapy in Murine Models of Circadian Disruption Resembling Delirium*

Gile

Scott²,

Eckle³

2018

Critical Care Medicine

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Section: Discussionsupporting

confidence: 93%

The Period 2 Enhancer Nobiletin as Novel Therapy in Murine Models of Circadian Disruption Resembling Delirium*

Gile

Scott²,

Eckle³

2018

Critical Care Medicine

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“…Post-operative patients usually experience various sleep disturbances, including sleep-wake cycle disturbances [22]. There have been an increasing number of studies that have demonstrated that anaesthetics can disrupt the daily rhythm [23][24][25]. We also proved in this experiment that long-term isoflurane anaesthesia caused mice with ad libitum feeding an approximately 3 h acrophase delay and 40% amplitude decrease, and 76% diurnality score increase on D1 and returned back to baseline on D2.…”

Section: Discussionsupporting

confidence: 50%

Time-restricted feeding alters isoflurane-induced memory deficits

Song

Chu

Fang

et al. 2020

Translational Neuroscience

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Food consumption during the rest phase promotes circadian desynchrony, which is corrected with harmful physiological and mental disorders. Previously, we found that circadian desynchrony was involved in isoflurane-induced cognitive impairment. Here, we scheduled food access to modulate daily rhythm to examine its impact on isoflurane-induced cognitive impairments. Mice were randomly transferred to restricted feeding (RF) time groups: Control group (Zeitgeber time (ZT) 0–ZT24, ad libitum feeding), Day-Feeding group (ZT0–ZT12, misaligned feeding), and Night-Feeding group (ZT12–ZT24, aligned feeding). Then, some of them were subjected to 5 h of 1.3% isoflurane anaesthesia from ZT14 to ZT19 and were divided into the Control + Anes group, the Day-Feeding + Anes group, and the Night-Feeding + Anes group. Mini-Mitter was used to monitor the daily rhythm. Fear conditioning system was conducted to assess cognition of mice. We observed that the Night-Feeding group adapted to RF gradually, whereas the Day-Feeding group exhibited a disturbed daily rhythm. The Night-Feeding + Anes group exhibited a partially enhanced daily rhythm, whereas the Day-Feeding + Anes group exhibited sustained phase advances and diurnality score increase 7 days after isoflurane anaesthesia. Notably, in tests of hippocampus-dependent contextual memory, the Night-Feeding + Anes group demonstrated decreased deficits; the Day-Feeding + Anes group showed prolonged post-anaesthetic deficits 14 days after isoflurane anaesthesia. However, amygdala-dependent cued-fear conditioning post-anaesthesia was not altered by the RF schedule. In conclusion, we demonstrated that misaligned feeding disturbed the daily rhythm and led to persistent post-anaesthetic cognitive dysfunction. Aligned feeding enhanced the daily rhythm partially and improved post-anaesthetic cognitive dysfunction.

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“…Based on observations that anesthesia can alter the expression of circadian rhythm proteins [9, 10, 25] we exposed mice to anesthetics used frequently in the clinical setting. Experimental design and timeline of in vivo studies are given in Fig.…”

Section: Resultsmentioning

confidence: 99%

The Circadian PER2 Enhancer Nobiletin Reverses the Deleterious Effects of Midazolam in Myocardial Ischemia and Reperfusion Injury

Oyama

Bartman

Gile

et al. 2018

CPD

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Background: Recently, we identified the circadian rhythm protein Period 2 (PER2) in robust cardioprotection from myocardial ischemia (MI). Based on findings that perioperative MI is the most common major cardiovascular complication and that anesthetics can alter the expression of PER2, we hypothesized that an anesthesia mediated downregulation of PER2 could be detrimental if myocardial ischemia and reperfusion (IR) would occur. Methods and Results: We exposed mice to pentobarbital, fentanyl, ketamine, propofol, midazolam or isoflurane and determined cardiac Per2 mRNA levels. Unexpectedly, only midazolam treatment resulted in an immediate and significant downregulation of Per2 transcript levels. Subsequent studies in mice pretreated with midazolam using an in-situ mouse model for myocardial (IR)-injury revealed a significant and dramatic increase in infarct sizes or Troponin-I serum levels in the midazolam treated group when compared to controls. Using the recently identified flavonoid, nobiletin, as a PER2 enhancer completely abolished the deleterious effects of midazolam during myocardial IR-injury. Moreover, nobiletin treatment alone significantly reduced infarct sizes or Troponin I levels in wildtype but not in Per2−/− mice. Pharmacological studies on nobiletin like flavonoids revealed that only nobiletin and tangeritin, both found to enhance PER2, were cardioprotective in our murine model for myocardial IR-injury. Conclusion: We identified midazolam mediated downregulation of cardiac PER2 as an underlying mechanism for a deleterious effect of midazolam pretreatment in myocardial IR-injury. These findings highlight PER2 as a cardioprotective mechanism and suggest the PER2 enhancers nobiletin or tangeritin as preventative therapy for myocardial IR-injury in the perioperative setting where midazolam pretreatment occurs frequently.

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Characterization of sevoflurane effects on Per2 expression using ex vivo bioluminescence imaging of the suprachiasmatic nucleus in transgenic rats

Cited by 16 publications

References 23 publications

The Period 2 Enhancer Nobiletin as Novel Therapy in Murine Models of Circadian Disruption Resembling Delirium*

The Period 2 Enhancer Nobiletin as Novel Therapy in Murine Models of Circadian Disruption Resembling Delirium*

Time-restricted feeding alters isoflurane-induced memory deficits

The Circadian PER2 Enhancer Nobiletin Reverses the Deleterious Effects of Midazolam in Myocardial Ischemia and Reperfusion Injury

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