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Escitalopram Ameliorates Forskolin-Induced Tau Hyperphosphorylation in HEK239/tau441 Cells

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Abstract

To investigate the effect of escitalopram (a widely used and highly efficacious antidepressant from the SSRI class) on tau hyperphosphorylation, HEK293/tau441 cells were pretreated with 4 μM of forskolin for 2 h. Then we treated the cells with different doses of escitalopram (0, 5, 10, 20, 40, 80 μM) for 22 h. We measured the phosphorylation level of tau by Western blotting. It was shown that escitalopram could protect tau from hyperphosphorylation induced by pharmacological activation of protein kinase A (PKA) at a dose of 20, 40, and 80 μM in vitro. Interestingly, the same dose of escitalopram could also increase the level of serine-9-phosphorylated GSK-3β (inactive form) and the phosphorylation level of Akt at Ser473 (active form) with no significant change in the level of total GSK-3β and Akt. Unexpectedly, 5-hydroxytryptamine 1A receptor (5-HT1A) agonist 8-OH-DPAT did not decrease forskolin-induced tau hyperphosphorylation. Our results suggest that escitalopram can ameliorate forskolin-induced tau hyperphosphorylation, which is not through the typical 5-HT1A pathway, and Akt/GSK-3β signaling pathway is involved. These findings may support an effective role of antidepressants in the prevention of dementia associated with depression in patients.

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Acknowledgments

This work was supported in part by grants from the National Natural Science Foundation of China (30900447 and 91232707), grants from the National Basic Research Program of China (2013CB835103), Strategic Priority Research Program of Chinese Academy of Science (XDB02020002), “the Fundamental Research Funds for the Central Universities”, and “the ordinary university graduate research and innovation program in Jiangsu Province” (KYLX_0200).

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    Authors and Affiliations

    1. Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China

      Qing-Guo Ren, Yan-Juan Wang, Wei-Gang Gong & Zhi-Jun Zhang

    2. Department of Neurology, Wu Xi Branch of Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Wuxi, China

      Qing-Guo Ren & Qi-Da Zhou

    3. Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China

      Lin Xu

    4. Graduate School of Chinese Academy of Sciences, Beijing, China

      Lin Xu

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    Correspondence to Qing-Guo Ren or Zhi-Jun Zhang.

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    Qing-Guo Ren and Yan-Juan Wang contributed equally to this work.

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    Ren, QG., Wang, YJ., Gong, WG. et al. Escitalopram Ameliorates Forskolin-Induced Tau Hyperphosphorylation in HEK239/tau441 Cells. J Mol Neurosci 56, 500–508 (2015). https://doi.org/10.1007/s12031-015-0519-4

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