Journal
JOURNAL OF THE NEUROLOGICAL SCIENCES
Volume 269, Issue 1-2, Pages 105-112Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jns.2007.12.034
Keywords
Akt; triciribine; estrogen; stroke
Categories
Funding
- NINDS NIH HHS [R01 NS050505-03, R01 NS055215, R01 NS050505-02, R01 NS055215-03, R01 NS050505, R01 NS055215-01A1] Funding Source: Medline
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Activation of Akt has been implicated as a major contributor to neuronal survival after an ischemic insult. Numerous neuroprotective agents have been shown to augment Akt activity, suggesting that this protein represents a major mechanism of cellular salvage after injury. Estrogen is known to augment Akt, but the possibility that Akt plays a differential role in the male and female brain has yet to be evaluated. In this study, we employed both pharmacological and genetic approaches to investigate the role of Akt in stroke. Utilizing a focal stroke model we show that deletion of the Akt1 isoform does not affect stroke outcome in either male or female mice. Akt1 deficient mice had equivalent levels of phosphorylated Akt (p-Akt) when compared to their WT controls following stroke suggesting that alternative isoforms can compensate for Akt1 loss. Secondly, estrogen's neuroprotective effect is maintained in Akt1(-/-) mice and estrogen exposure did not enhance p-Akt levels in WT female mice. Thirdly, we show that inhibiting Akt using the direct pan-Akt inhibitor triciribine has no effect on stroke outcome despite dramatic reductions in p-Akt. Our study demonstrates the limitations of genetic mouse models and suggests that the importance of Akt to ischemic outcome remains unclear. (C) 2007 Elsevier B.V. All rights reserved.
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