Neural Regeneration Research ›› 2013, Vol. 8 ›› Issue (34): 3173-3182.doi: 10.3969/j.issn.1673-5374.2013.34.001

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Phosphorylation of tau protein over time in rats subjected to transient brain ischemia

Bo Song1, 2, Qiang Ao1, 3, Zhen Wang3, Weiqiang Liu3, Ying Niu2, Qin Shen4, Huancong Zuo1, Xiufang Zhang2, Yandao Gong2   

  1. 1 Institute of Neurology Disorders, Yuquan Hospital, Tsinghua University, Beijing 100049, China
    2 State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China
    3 Center for Advanced Materials and Biotechnology, Research Institute of Tsinghua University in Shenzhen, Shenzhen High-Tech Industrial Estate, Shenzhen 518057, China
    4Medical School, Tsinghua University, Beijing 100084, China
  • Received:2013-08-30 Revised:2013-11-20 Online:2013-12-05 Published:2013-12-05
  • Contact: Qiang Ao, M.D., Associate professor, Institute of Neurology Disorders, Yuquan Hospital, Tsinghua University, Beijing 100049, China, aoqiang@tsinghua.edu.cn. Yandao Gong, Master, Professor, State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China, gongyd@tsinghua. edu.cn.
  • About author:Bo Song, M.D., Assistant researcher.
  • Supported by:

    This work was supported by the National High Technology Research and Development Program of China (863 Program), No. 2012AA020905; the Biological Industry Development Funds of Shenzhen, No. JC201005260093A; the National Natural Science Foundation of China/Research Grants Council Joint Research Scheme, No. 81161160570; the National Natural Science Foundation of China, No. 81171143; and the Tsinghua-Yue-Yuen Medical Sciences Fund.

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Abstract:

Transient brain ischemia has been shown to induce hyperphosphorylation of the microtu-bule-associated protein tau. To further determine the mechanisms underlying these processes, we investigated the interaction between tau, glycogen synthase kinase (GSK)-3β and protein phos-phatase 2A. The results confirmed that tau protein was dephosphorylated during brain ischemia; in addition, the activity of GSK-3β was increased and the activity of protein phosphatase 2A was de-creased. After reperfusion, tau protein was hyperphosphorylated, the activity of GSK-3β was de-creased and the activity of protein phosphatase 2A remained low. Importantly, the interaction of tau with GSK-3β and protein phosphatase 2A was altered during ischemia and reperfusion. Lithium chloride could affect tau phosphorylation by regulating the interaction of tau with GSK-3β and pro-tein phosphatase 2A, and improve learning and memory ability of rats after transient brain ischemia. The present study demonstrated that it was the interaction of tau with GSK-3β and protein phos-phatase 2A, rather than their individual activities, that dominates the phosphorylation of tau in tran-sient brain ischemia. Hyperphosphorylated tau protein may play an important role in the evolution of brain injury in ischemic stroke. The neuroprotective effects of lithium chloride partly depend on the inhibition of tau phosphorylation during transient brain ischemia.

Key words: neural regeneration, brain injury, brain ischemia, reperfusion, microtubule-associated protein tau, phosphorylation, glycogen synthase kinase 3β, protein phosphatase 2A, lithium chloride, grants-supported paper, neuroregeneration