Ginkgo biloba Extract EGb761 Attenuates Hyperhomocysteinemia-induced AD Like Tau Hyperphosphorylation and Cognitive Impairment in Rats

Title:Ginkgo biloba Extract EGb761 Attenuates Hyperhomocysteinemia-induced AD Like Tau Hyperphosphorylation and Cognitive Impairment in Rats

Volume: 15 Issue: 1

Author(s): Kuan Zeng, Mengzhu Li, Jichang Hu, Yacoubou Abdoul Razak Mahaman, Jian Bao, Fang Huang, Yiyuan Xia, Xinghua Liu, Qun Wang, Jian-Zhi Wang, Yang Yang, Rong Liu and Xiaochuan Wang*

Affiliation:

• Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030,China

Keywords: Ginkgo biloba extract EGb761, Alzheimer's disease (AD), hyperhomocysteinemia (HHcy), tau hyperphosphorylation, cognitive impairment, oxidative damage.

Abstract: Background: Ginkgo biloba extract EGb761 has shown the neuroprotective effects on Alzheimer's disease (AD) through the protection against the Aβ-induced neurotoxicity. However, it is not completedly clear whether EGb761 attenuates tau hyperphosphorylation, another of the most prominent mechanisms underlying the pathology of AD.

Methods: we employed hyperhomocysteinemia (HHcy) to mimic AD like pathological alterations and memory deficits in rats as model, and injected EGb761 with or after HHcy injection as prevention and treatment, injected saline as control. We measured the status of oxidative damage and spatial and learning memory in rats. Then we detected the level of memory-related proteins, tau phosphorylation and the level and activity of tau kinase (GSK-3β) and phosphatase (PP2A) by Western blotting and Immunohistochemistry.

Results: We found that EGb761 could significantly antagonize HHcy-induced oxidative damage, recover PP2Ac and GSK3β activities deregulated by HHcy. Furthermore, tau was hyperphosphorylated at Thr231, Ser262, Ser396, and Ser404, most common PP2Ac and GSK3β targeted sites in the hippocampus and prefrontal cortex of HHcy rats, whereas EGb761 recovered the tau phosphorylation at those sites. Behavioral tests revealed that EGb761 rescued HHcy-induced spatial reference memory deficit and upregulated the expression of synapse-associated protein PSD95 and synapsin-1.

Conclusion: EGb761 might be a promising drug to treat AD through its anti-oxidative activity and decreasing tau hyperphosphorylation besides the protection against the Aβ-induced neurotoxicity.

Cite this article as:

Zeng Kuan , Li Mengzhu, Hu Jichang , Mahaman Abdoul Razak Yacoubou , Bao Jian , Huang Fang , Xia Yiyuan, Liu Xinghua , Wang Qun, Wang Jian-Zhi , Yang Yang, Liu Rong and Wang Xiaochuan *, Ginkgo biloba Extract EGb761 Attenuates Hyperhomocysteinemia-induced AD Like Tau Hyperphosphorylation and Cognitive Impairment in Rats, Current Alzheimer Research 2018; 15 (1) . https://dx.doi.org/10.2174/1567205014666170829102135