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

Jia Song1, Shuaishuai Chu1, Yin Cui1

  • 1Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department of Nanjing University, 321 Zhong Shan Road, Nanjing, Jiangsu 210008, PR China.

Experimental Neurology
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Advanced age exacerbates postoperative cognitive dysfunction (POCD) by prolonging anesthesia-induced circadian disruption. Melatonin treatment can prevent this impairment by restoring circadian rhythms in aged mice.

Keywords:
circadian rhythmcognition dysfunctionisofluranemelatonin

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Area of Science:

  • Neuroscience
  • Gerontology
  • Anesthesiology

Background:

  • Postoperative cognitive dysfunction (POCD) is a prevalent clinical issue, particularly in elderly patients undergoing anesthesia and surgery.
  • Advanced age is a significant risk factor for POCD, with disrupted circadian rhythms implicated in memory impairment after anesthesia.

Purpose of the Study:

  • To investigate if advanced age increases POCD risk through prolonged post-anesthetic circadian disruption.
  • To evaluate the potential of melatonin in preventing anesthesia-induced cognitive deficits and circadian disruption in aged mice.

Main Methods:

  • Aged and young mice were subjected to 5-hour isoflurane anesthesia to model POCD.
  • Cognitive function was assessed using novel object recognition and Morris water maze tests.
  • Circadian rhythms of gross motor activity and body temperature were monitored, with melatonin pretreatment in aged mice.

Main Results:

  • Aged mice exhibited prolonged cognitive deficits (over 1 week) compared to young mice (3 days) after anesthesia.
  • Anesthesia caused a 3-day phase shift in motor activity and temperature rhythms in aged mice, lasting longer than in young mice.
  • Melatonin pretreatment prevented cognitive impairment in aged mice by restoring circadian rhythms and resynchronizing clock genes.

Conclusions:

  • Long-term anesthesia induces more severe and prolonged memory deficits and circadian disruption in aged mice.
  • Melatonin effectively prevents isoflurane-induced cognitive impairments in aged mice by resynchronizing circadian rhythms.