Activation of Akt/FoxO signaling pathway contributes to induction of neuroprotection against transient global cerebral ischemia by hypoxic pre-conditioning in adult rats
Article first published online: 18 MAY 2010
© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry
Journal of Neurochemistry
Volume 114, Issue 3, pages 897–908, August 2010
How to Cite
Zhan, L., Wang, T., Li, W., Xu, Z. C., Sun, W. and Xu, E. (2010), Activation of Akt/FoxO signaling pathway contributes to induction of neuroprotection against transient global cerebral ischemia by hypoxic pre-conditioning in adult rats. Journal of Neurochemistry, 114: 897–908. doi: 10.1111/j.1471-4159.2010.06816.x
- Issue published online: 6 JUL 2010
- Article first published online: 18 MAY 2010
- Received January 24, 2010; revised manuscript received May 10, 2010; accepted May 11, 2010.
- forkhead transcription factors;
- hypoxic pre-conditioning;
- ischemic tolerance;
- protein kinase B
J. Neurochem. (2010) 114, 897–908.
It is well established that pre-conditioning protects neuronal injury against ischemia. However, the molecular mechanisms underlying ischemic tolerance are not completely understood. The purpose of the present study was to investigate the role of Akt/forkhead transcription factor, class O (FoxO) pathway in hypoxic pre-conditioning (HPC) using a newly developed HPC to transient global cerebral ischemia (tGCI) model in adult rats. HPC for 30–120 min significantly reduced cell death in the CA1 subregion after 10 min of tGCI. HPC was effective only when applied 1–4 days before ischemia. The maximum protection was observed with 30 min of hypoxia and 1 day interval between hypoxia and ischemia. The phosphorylated Akt and FoxOs measured by western blot and immunohistochemistry were significantly increased after hypoxia-ischemia except for a transient decrease in the HPC group. Lateral ventricular infusion of LY294002 before HPC blocked the increase in phosphorylated Akt and FoxOs and increased neuronal damage in HPC animals. These results suggest that pre-exposure to hypoxia induces protection against tGCI in adult rats. Activation of Akt results in the inactivation of FoxOs which may mediate ischemic tolerance after HPC.