Ginsenoside Rd attenuates tau protein phosphorylation via the PI3K/AKT/GSK-3β pathway after transient forebrain ischemia.

Abstract

Phosphorylated tau was found to be regulated after cerebral ischemia and linked to high risk for the development of post-stroke dementia. Our previous study showed that ginsenoside Rd (Rd), one of the main active ingredients in Panax ginseng, decreased tau phosphorylation in Alzheimer model. As an extending study, here we investigated whether Rd could reduce tau phosphorylation and sequential cognition impairment after ischemic stroke. Sprague-Dawley rats were subjected to focal cerebral ischemia. The tau phosphorylation of rat brains were analyzed following ischemia by Western blot and animal cognitive functions were examined by Morris water maze and Novel object recognition task. Ischemic insults increased the levels of phosphorylated tau protein at Ser199/202 and PHF-1 sites and caused animal memory deficits. Rd treatment attenuated ischemia-induced enhancement of tau phosphorylation and ameliorated behavior impairment. Furthermore, we revealed that Rd inhibited the activity of Glycogen synthase kinase-3β (GSK-3β), the most important kinase involving tau phosphorylation, but enhanced the activity of protein kinase B (PKB/AKT), a key kinase suppressing GSK-3β activity. Moreover, we found that LY294002, an antagonist for phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, abolished the inhibitory effect of Rd on GSK-3β activity and tau phosphorylation. Taken together, our findings provide the first evidence that Rd may reduce cerebral ischemia-induced tau phosphorylation via the PI3K/AKT/GSK-3β pathway.

• Authors: Xiao Zhang, Ming Shi, Ruidong Ye, Wei Wang, Xuedong Liu, Guangyun Zhang, Junliang Han, Yunxia Zhang, Bing Wang, Jun Zhao, Juan Hui, Lize Xiong, Gang Zhao
• Journal: Neurochemical research (Neurochem Res) Vol. 39 Issue 7 Pg. 1363-73 (Jul 2014) ISSN: 1573-6903 [Electronic] United States
• PMID: 24792734 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ginsenosides
• tau Proteins
• Phosphatidylinositol 3-Kinases
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, rat
• Oncogene Protein v-akt
• Glycogen Synthase Kinase 3
• ginsenoside Rd

Topics

• Animals
• Ginsenosides (pharmacology, therapeutic use)
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Ischemic Attack, Transient (drug therapy, metabolism)
• Male
• Oncogene Protein v-akt (metabolism)
• Panax
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation (drug effects, physiology)
• Prosencephalon (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• tau Proteins (antagonists & inhibitors, metabolism)