Icariin sustains the proliferation and differentiation of Aβ25-35-treated hippocampal neural stem cells via the BDNF-TrkB-ERK/Akt signaling pathway

Abstract

ABSTRACT Objectives Icariin (ICA) can be potentially used to treat Alzheimer’s disease (AD), but the mechanism was not clear. The current study explored the effects of ICA on hippocampal neural stem cells, aiming to provide a comprehensive basis for its clinical application. Methods Hippocampal neural stem cells were isolated from newborn rats and their differentiation ability was evaluated by performing immunofluorescence staining. Next, Aβ cell model was constructed by treating the cells with Aβ25-35, and then the model was further treated by ICA or shBDNF or the two in combination. The viability and differentiation of the cells were, respectively, analyzed by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT) and flow cytometry. The expression of BDNF-TrkB-ERK/Akt signaling pathway was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot (WB). Results The hippocampal neural stem cells can differentiate into neurons and astrocytes. ICA effectively promoted the viability and differentiation of Aβ cell models. The expression levels of BDNF and TrkB in Aβ cell models were obviously decreased, which were noticeably increased by ICA. Moreover, BDNF knockdown further inhibited the viability and differentiation of Aβ model cells, which could be reversed by ICA. BDNF knockdown not only suppressed the expressions of BDNF and TrkB in Aβ cell models but also effectively prevented the phosphorylation of ERK/Akt; however, these phenomena were significantly alleviated by ICA treatment. Discussion ICA promoted the proliferation and differentiation of Aβ25-35-treated hippocampal neural stem cells through BDNF-TrkB-ERK/Akt signaling pathway. The current findings might contribute to the treatment of AD.