Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Escitalopram attenuates β-amyloid-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3β pathway

Yan-Juan Wang, Qing-Guo Ren, Wei-Gang Gong, Di Wu, Xiang Tang, Xiao-Li Li, Fang-Fang Wu, Feng Bai, Lin Xu and Zhi-Jun Zhang _

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Oncotarget. 2016; 7:13328-13339. https://doi.org/10.18632/oncotarget.7798

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Abstract

Yan-Juan Wang1,*, Qing-Guo Ren1,*, Wei-Gang Gong1, Di Wu1, Xiang Tang1, Xiao-Li Li1, Fang-Fang Wu1, Feng Bai1, Lin Xu2 and Zhi-Jun Zhang1,3

1 Department of Neurology, ZhongDa Hospital, Neuropsychiatric Institute, Medical School of Southeast University, Nanjing, China

2 Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming, China

3 Center of Schizophrenia, Beijing Institute for Brain Disorders, Beijing, China

* These authors have contributed equally to this work

Correspondence to:

Zhi-Jun Zhang, email:

Qing-Guo Ren, email:

Keywords: Alzheimer’s disease, tau protein, escitalopram, Akt/GSK-3β pathway, 5-HT1A receptor, Gerotarget

Received: January 04, 2016 Accepted: February 18, 2016 Published: February 29, 2016

Abstract

Tau hyperphosphorylation is an important pathological feature of Alzheimer’s disease (AD). To investigate whether escitalopram could inhibit amyloid-β (Aβ)-induced tau hyperphosphorylation and the underlying mechanisms, we treated the rat primary hippocampal neurons with Aβ1-42 and examined the effect of escitalopram on tau hyperphosphorylation. Results showed that escitalopram decreased Aβ1–42-induced tau hyperphosphorylation. In addition, escitalopram activated the Akt/GSK-3β pathway, and the PI3K inhibitor LY294002 blocked the attenuation of tau hyperphosphorylation induced by escitalopram. Moreover, the 5-HT1A receptor agonist 8-OH-DPAT also activated the Akt/GSK-3β pathway and decreased Aβ1-42-induced tau hyperphosphorylation. Furthermore, the 5-HT1A receptor antagonist WAY-100635 blocked the activation of Akt/GSK-3β pathway and the attenuation of tau hyperphosphorylation induced by escitalopram. Finally, escitalopram improved Aβ1–42 induced impairment of neurite outgrowth and spine density, and reversed Aβ1–42 induced reduction of synaptic proteins. Our results demonstrated that escitalopram attenuated Aβ1–42-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3β pathway.


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