Escitalopram attenuates β-amyloid-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT(1A) receptor mediated Akt/GSK-3β pathway

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 Aβ(1-42) and examined the effect of escitalopram on tau hyperphosphorylation. Results showed that escitalopram decreased Aβ(1–42)-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-HT(1A) receptor agonist 8-OH-DPAT also activated the Akt/GSK-3β pathway and decreased Aβ(1-42)-induced tau hyperphosphorylation. Furthermore, the 5-HT(1A) receptor antagonist WAY-100635 blocked the activation of Akt/GSK-3β pathway and the attenuation of tau hyperphosphorylation induced by escitalopram. Finally, escitalopram improved Aβ(1–42) induced impairment of neurite outgrowth and spine density, and reversed Aβ(1–42) induced reduction of synaptic proteins. Our results demonstrated that escitalopram attenuated Aβ(1–42)-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT(1A) receptor mediated Akt/GSK-3β pathway.