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KMID : 1204320130290020063
Laboratory Animal Research
2013 Volume.29 No. 2 p.63 ~ p.69
Ferulic acid regulates the AKT/GSK-3¥â/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model
Gim Sang-Ah

Sung Jin-Hee
Shah Fawad Ali
Kim Myeong-Ok
Koh Phil-Ok
Abstract
Ferulic acid, a component of the plants Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort, exerts a neuroprotective effect by regulating various signaling pathways. This study showed that ferulic acid treatment prevents the injury-induced increase of collapsin response mediator protein 2 (CRMP-2) in focal cerebral ischemia. Glycogen synthase kinase-3¥â (GSK-3¥â) regulates CRMP-2 function through phosphorylation of CRMP-2. Moreover, the pro-apoptotic activity of GSK-3¥â is inactivated by phosphorylation by Akt. This study investigated whether ferulic acid modulates the expression of CRMP-2 and its upstream targets, Akt and GSK-3¥â, in focal cerebral ischemia. Male rats were treated immediately with ferulic acid (100 mg/kg, i.v.) or vehicle after middle cerebral artery occlusion (MCAO), and then cerebral cortices were collected 24 hr after MCAO. MCAO resulted in decreased levels of phospho-Akt and phospho-GSK-3¥â, while ferulic acid treatment prevented the decrease in the levels of these proteins. Moreover, phospho-CRMP-2 and CRMP-2 levels increased during MCAO, whereas ferulic acid attenuated these injury-induced increases. These results demonstrate that ferulic acid regulates the Akt/GSK-3¥â/CRMP-2 signaling pathway in focal cerebral ischemic injury, thereby protecting against brain injury.
KEYWORD
Ferulic acid, neuroprotection, Akt, GSK-3¥â, CRMP-2
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