Isoflurane anesthesia in aged mice and effects of A1 adenosine receptors on cognitive impairment

Summary Aims Isoflurane may not only accelerate the process of Alzheimer's disease (AD), but increase the risk of incidence of postoperative cognitive dysfunction (POCD). However, the underlying mechanisms remain unknown. This study was designed to investigate whether isoflurane contributed to...

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Published in:CNS neuroscience & therapeutics 2018-03, Vol.24 (3), p.212-221
Main Authors: Zuo, Chun‐Long, Wang, Chun‐Man, Liu, Jin, Shen, Ting, Zhou, Jiang‐Ping, Hao, Xin‐Rui, Pan, Yi‐Zhao, Liu, Hua‐Cheng, Lian, Qing‐Quan, Lin, Han
Format: Article
Language:English
Subjects:
Adenosine
adenosine A1
Aging - drug effects
Aging - metabolism
Aging - psychology
Alzheimer's disease
Amyloid beta-Peptides - metabolism
Anesthesia
Anesthetics, Inhalation - toxicity
Animals
Cognitive ability
cognitive dysfunction
Cognitive Dysfunction - etiology
Cognitive Dysfunction - metabolism
Glutamic acid receptors (ionotropic)
hippocampus
Isoflurane
Isoflurane - toxicity
Male
Maze Learning - drug effects
Maze Learning - physiology
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Knockout
N-Methyl-D-aspartic acid receptors
Neurodegenerative diseases
Original
Phosphorylation
Random Allocation
receptor
Receptor, Adenosine A1 - genetics
Receptor, Adenosine A1 - metabolism
Receptors, N-Methyl-D-Aspartate - metabolism
Rodents
Spatial memory
Tau protein
tau Proteins - metabolism
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Summary:Summary Aims Isoflurane may not only accelerate the process of Alzheimer's disease (AD), but increase the risk of incidence of postoperative cognitive dysfunction (POCD). However, the underlying mechanisms remain unknown. This study was designed to investigate whether isoflurane contributed to the POCD occurrence through A1 adenosine receptor (A1AR) in aged mice. Methods We assessed cognitive function of mice with Morris water maze (MWM) and then measured expression level of two AD biomarkers (P‐tau and Aβ) and a subtype of the NMDA receptor (NR2B) in aged wild‐type (WT) and homozygous A1 adenosine receptor (A1AR) knockout (KO) mice at baseline and after they were exposed to isoflurane (1.4% for 2 hours). Results For cognitive test, WT mice with isoflurane exposure performed worse than the WT mice without isoflurane exposure. However, A1AR KO mice with isoflurane exposure performed better than WT mice with isoflurane exposure. WT mice exposed to isoflurane had increased levels of Aβ and phosphorylated tau (P‐tau). Levels of Aβ and P‐tau were decreased in A1AR KO mice, whereas no differences were noted between KO mice with and without isoflurane exposure. NR2B expression was inversely related to that of P‐tau, with no differences found between KO mice with and without isoflurane exposure. Conclusions We found an association between isoflurane exposure, impairment of spatial memory, decreasing level of NR2B, and increasing levels of A‐beta and P‐tau, presumably via the activation of the A1A receptor.
ISSN:1755-5930
1755-5949
DOI:10.1111/cns.12794