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

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 <i>in vitro</i> and <i>in vivo</i>. 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 <i>in vitro</i>. Knockdown of BACE1-AS mediated by lentivirus <i>in vivo</i> 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.