Effect of chronic intermittent hypoxia on AMPK pathway in young rats
10.3969/j.issn.1000-4718.2016.07.008
- VernacularTitle:慢性间歇性低氧对幼鼠脑区 AMPK通路的影响
- Author:
Dongshi LIANG
;
Liya CHEN
;
Fangfang HONG
;
Jing LIN
;
Zhengwang WEN
;
Xiucui LI
;
Xiaohong CAI
- Publication Type:Journal Article
- Keywords:
Chronic intermittent hypoxia;
Adenosine A2a receptor;
AMP-activated protein kinase;
Mamma-lian target of rapamycin;
Hippocampus;
Prefrontal cortex
- From:
Chinese Journal of Pathophysiology
2016;32(7):1200-1207
- CountryChina
- Language:Chinese
-
Abstract:
[ ABSTRACT] AIM: To investigate the effect of chronic intermittent hypoxia on AMP-activated protein kinase ( AMPK) pathway in the brain of young rats.METHODS:Part one:SD mice (3~4 weeks old) were randomly divided into 4 groups (n=8): simulated air control group for 2 weeks (2AC), chronic intermittent hypoxia group for 2 weeks (2IH), simulated air control group for 4 weeks (4AC) and chronic intermittent hypoxia group for 4 weeks (4IH).Part two:SD mice (3~4 weeks old) were randomly divided into 2 groups (n=8): chronic intermittent hypoxia group for 4 weeks (4IH) and chronic intermittent hypoxia group treated with AMPK inhibitor for 4 weeks (4IHI).After modeling, the eight-arm maze test was performed.TUNEL method was used to detect the neuronal apoptosis in the hippocampal and pre-frontal cortical tissues.The mRNA expression of adenosine A2a receptor was examined by RT-qPCR, and the protein levels of phosphorylated AMPK (p-AMPK) and mammalian target of rapamycin (p-mTOR) were determined by Western blot.
RESULTS:Compared with control group, the numbers of reference memory error ( RME) , working memory error ( WME) and total error (TE) in 2IH group and 4IH group significantly increased (P<0.01).Compared with 2IH group, the num-bers of errors in 4IH group also increased significantly (P<0.01).Compared with 4IH group, the values in 4IHI group significantly decreased.Compared with control group, the neuronal apoptosis of hippocampus and prefrontal cortex in 2IH group and 4IH group increased, and that in 4IH group was more evident (P<0.05).In 4IHI group, the neuronal apopto-sis decreased.The mRNA expression of adenosine A2a receptor in the hippocampal and cortical tissues in 2IH group and 4IH group was higher than that in control group.The protein level of p-AMPK was higher, and p-mTOR was lower in 2IH group and 4IH group, and those in 4IH group were more evident (P<0.05).Compared with 4IH group, the protein level of p-AMPK was lower, and p-mTOR was higher in 4IHI group.CONCLUSION: Chronic intermittent hypoxia induces neuronal apoptosis, resulting in impairment of learning and memory in a time-dependent manner by upregulating adenosine A2a receptor, activating AMPK activity, and inhibiting mTOR phosphorylation in rats.
