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论文题目: Escitalopram Ameliorates Forskolin-Induced Tau Hyperphosphorylation in HEK239/tau441 Cells
作者: Qing-Guo Ren*; Yan-Juan Wang; Wei-Gang Gong; Qi-Da Zhou; Lin Xu; Zhi-Jun Zhang*
联系作者: rqg1976@tom.com; zhijunzhang@seu.edu.cn
发表年度: 2015
DOI:
摘要: 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 mu M of forskolin for 2 h. Then we treated the cells with different doses of escitalopram (0, 5, 10, 20, 40, 80 mu M) 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 mu M in vitro. Interestingly, the same dose of escitalopram could also increase the level of serine-9-phosphorylated GSK-3 beta (inactive form) and the phosphorylation level of Akt at Ser473 (active form) with no significant change in the level of total GSK-3 beta 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-3 beta signaling pathway is involved. These findings may support an effective role of antidepressants in the prevention of dementia associated with depression in patients.
刊物名称: Journal of Molecular Neuroscience
论文出处:
影响因子: 2.343 (2014)