Knockdown of BACE1‑AS by siRNA improves memory and learning behaviors in Alzheimer's disease animal model

Zhang,Wenting; Zhao,Hao; Wu,Qian; Xu,Wenan; Xia,Minwu

doi:10.3892/etm.2018.6359

Knockdown of BACE1‑AS by siRNA improves memory and learning behaviors in Alzheimer's disease animal model

Authors:
- Wenting Zhang
- Hao Zhao
- Qian Wu
- Wenan Xu
- Minwu Xia
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Affiliations: Department of Neurology, Hefei Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230000, P.R. China
Published online on: June 27, 2018 https://doi.org/10.3892/etm.2018.6359
Pages: 2080-2086

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Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disease that causes progressive damage to neurons. Emerging evidence has demonstrated that long non‑coding RNAs (lncRNAs) serve an important role in many neurological diseases, such as AD. β‑secretase 1 (BACE1)‑antisense transcript (BACE1‑AS) was identified as a conserved non‑coding antisense BACE1. Previous reports stated that BACE1‑AS positively regulated BACE1 mRNA and subsequently BACE1 protein expression in vitro and in vivo. However, whether BACE1‑AS is able to regulate memory and learning behaviors remains to be elucidated. In the present study, the role of lncRNA BACE1‑AS on memory and learning was investigated. It was demonstrated that lncRNA BACE1‑AS expression was highly expressed in blood samples from AD patients, and also upregulated in peripheral blood samples and hippocampi from an AD animal model. Knockdown of BACE1‑AS by short interfering RNA increased the primary hippocampal neurons proliferation in vitro. Knockdown of BACE1‑AS mediated by lentivirus in vivo improved the memory and learning behaviors of SAMP8 mice, inhibited BACE1 and amyloid precursor protein production, and phosphorylation of tau protein in hippocampi. Therefore, the present findings suggested that BACE1‑AS may be a potential target for management of memory loss related diseases, such as AD.

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