Chun-Long Zuo1,2, Chun-Man Wang1,2, Jin Liu1,2, Ting Shen1,2, Jiang-Ping Zhou1,2, Xin-Rui Hao1,2, Yi-Zhao Pan1,2, Hua-Cheng Liu1,2, Qing-Quan Lian1,2, Han Lin1,2. 1. Department of Anesthesiology, Critical Care and Pain Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China. 2. Zhejiang Province Key Lab of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Abstract
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.
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.
Authors: Brian A Warmus; Dheepa R Sekar; Eve McCutchen; Gerard D Schellenberg; Rosalinda C Roberts; Lori L McMahon; Erik D Roberson Journal: J Neurosci Date: 2014-12-03 Impact factor: 6.167