The expression of PI3K/AKT pathway and the correlation with cognitive impairment after HIBD in rats

YAO Dan; ZHANG Wei; HE Xue; WANG Jinhu; JIANG Kewen; ZHAO Zhengyan

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The expression of PI3K/AKT pathway and the correlation with cognitive impairment after HIBD in rats

YAO Dan #,ZHANG Wei #,HE Xue #,WANG Jinhu #,JIANG Kewen #,ZHAO Zhengyan *

Department of Pediatric Healthy Care, The Children's Hospital, Zhejiang University School of Medicine

*Correspondence author

#Submitted by

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Funding: Specialized Research Fund For the Doctoral Programe of Higher Education（No.No.200803350106）, National Natural Science Foundation（No.No.30970963 /C09090205）

Opened online:28 February 2012

Accepted by: none

Citation: YAO Dan,ZHANG Wei,HE Xue.The expression of PI3K/AKT pathway and the correlation with cognitive impairment after HIBD in rats[OL]. [28 February 2012] http://en.paper.edu.cn/en_releasepaper/content/4467914

Since the phosphoinositid 3-kinase/Akt (PI3K/Akt) signaling pathway and PTEN gene have been known to be closely related to hypoxia-ischemia brain injury, we hypothesized that they are involved in neonatal hypoxic ischemic brain damage (HIBD) and as well as cognitive impairment. To test this hypothesis, 7 day old newborn rats were subjected to HIBD by ligating the common carotid artery followed by hypoxia. Rat brains were collected to detect the expression of PI3K/Akt and PTEN using Western blot analysis. The expression of p-Akt and p-PTEN were found to be significantly upregulated after hypoxia-ischemia (HI) compared with the sham operation group. However the expression of p-Akt peaked at 4h, earlier than p-PTEN which is at 12h. p-Akt protein was significantly inhibited after blocking the PI3K/Akt signaling pathway using a specific inhibitor called wortmannin. Through the Morris Water Maze (MWM) test, showed that the rats' learning and memory cognitive abilities were impaired after HI, and the cognitive impairment were more severe after blocking the PI3K/Akt signaling pathway. Our findings suggest that the PI3K/Akt signaling pathway and PTEN gene play important roles to cognitive impairment in HIBD.

Keywords:Neonatal rat；Hypoxia-ischemic; PI3K/Akt; PTEN; Inhibitor; Morris water maze

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