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Ginsenoside Rd Attenuates Tau Protein Phosphorylation Via the PI3K/AKT/GSK-3β Pathway After Transient Forebrain Ischemia

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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.

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Acknowledgments

The authors are grateful to Ms. Dongyun Feng for technical assistance. This study was supported by the National Natural Science Foundation of China (Nos. 81171236, 81371365, 31170801, and 31300900) and Program for Changjiang Scholars and Innovative Research Team in University (No. IRT1053).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, Xijing Hospital, Forth Military Medical University, Xi’an, People’s Republic of China

    Xiao Zhang, Ming Shi, Xuedong Liu, Guangyun Zhang, Junliang Han, Yunxia Zhang, Bing Wang, Jun Zhao, Juan Hui & Gang Zhao

  2. Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, People’s Republic of China

    Ruidong Ye

  3. Department of Microbiology, Institute of Clinical Medicine, Oslo University Hospital, Oslo, Norway

    Wei Wang

  4. Department of Anesthesiology, Xijing Hospital, Forth Military Medical University, Xi’an, People’s Republic of China

    Lize Xiong

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  1. Xiao Zhang
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Correspondence to Ming Shi or Gang Zhao.

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Zhang, X., Shi, M., Ye, R. et al. Ginsenoside Rd Attenuates Tau Protein Phosphorylation Via the PI3K/AKT/GSK-3β Pathway After Transient Forebrain Ischemia. Neurochem Res 39, 1363–1373 (2014). https://doi.org/10.1007/s11064-014-1321-3

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