Issue Archive

Ginsenoside Rb1 attenuates okadaic acid--induced Tau protein hyperphosphorylation in rat hippocampal neurons

Li Yongkun, Chen Xiaochun, Zhu Yuangui, Peng Xiaosong, Zeng Yuqi, Shen Jie, Huang Tianwen

The Affiliated Union Hospital of Fujian Medical University, Fujian Institute of Geriatrics.Fuzhou 350001,Fujian

Abstract

The present study was aimed to investigate the effects of ginsenoside Rb1 on okadaic acid (OA)-induced Tau hyperphosphorylation in Sparague Dawley rat hippocampal neurons and to explore its possible mechanism. Animals were randomly divided into four groups. Group 1 received dimethysulphoxide (DMSO) injection (Vehicle group), Group 2 only received OA injection (OA group), Group 3 was pretreated with Rb1 and then received OA injection (Rb1 pretreatment group), and the Group 4 was an intact control group. The animals in Group 3 were injected intraperitoneally with various doses of Rb1 at 5, 10, or 20 mg/kg (once a day for 14 days). On the thirteen day of pretreatment, animals in Rb1 pretreatment group as well as animals in OA group received a bolus injection of 0.483 #mu#g of OA (1.5 #mu#l of solution in DMSO) at right dorsal aspect of hippocampus to induce Tau hyperphosphrylation. The brains were harvested one day after the last treatment. In all groups, the morphology of neurofibrils, phosphorylation of Tau protein, and the activity of phosphatase 2A (PP2A) were investigated. In OA group, the Bielschowski's assay revealed darkened and uneven neurofibrils staining in the hippocampus. The immunohistochemistry results showed a significant increase in Thr~(231) phosphorylation of Tau protein in OA group relative to the control group (P<0.01). OA injection also markedly decreased PP2A activity (P<0.01). Western blot confirmed Thr~(231) phosphorylation of Tau protein and it also detected phosphorylation of Ser~(396) of Tau protein. The animals with Rb1 pretreatment displayed even staining of neurofibrils and normal pattern of fiber organization. Rb1 pretreatment also attenuated Thr~(231) and Ser~(396) hyperphosphorylations of Tau protein, and restored PP2A activity compared to the OA group (P<0.01). These results indicate that OA-induced hyperphosphorylation of Tau protein in rat hippocampal neurons can be attenuated by the pretreatment of ginsenoside Rb1. These data also implicate that Rb1 has potential neuroprotective effects on Tau-related neuropathology.

Key words: Ginsenoside Rb1;Alzheimer disease;Okadaic acid;Tau proteins;Phosphorylation;Protein Phosphatase-2A

Received: 　　Accepted:

Corresponding author: 　　E-mail:

Citing This Article：

Li Yongkun, Chen Xiaochun, Zhu Yuangui, Peng Xiaosong, Zeng Yuqi, Shen Jie, Huang Tianwen. Ginsenoside Rb1 attenuates okadaic acid--induced Tau protein hyperphosphorylation in rat hippocampal neurons. Acta Physiol Sin 2005; 57 (2): (in Chinese with English abstract).