Neuroprotective effects of bajijiasu against cognitive impairment induced by amyloid-β in APP/PS1 mice.

Haobin Cai,Tiantian Cai,Jiayang He,Rong Zhang,Zhouke Guo,Jiansong Fang,Jun Wu,Huafeng Pan,Qi Wang,Yijie Wang,Qinkai Zhan,Li Guan,Yao Xiao,Li Lin

doi:10.18632/oncotarget.21515

Abstract

Alzheimer's disease (AD) is a progressive neurological degenerative disease. The main clinical manifestations of AD include progressive cognitive impairment and alteration of personality. Senile plaques, neuroinflammation, and destruction of synapse structure stability are the main pathological features of AD. Bajijiasu(BJJS) is extracted from Morinda Officinalis, a Chinese herb. In this study, we explored the effect of BJJS on AD from many aspects in APPswe/PSEN1ΔE9 (APP/PS1) double transgenic mice. The Morris water maze and novel object recognition tests results showed that BJJS could significantly improve the learning and memory abilities in APP/PS1 mice. BJJS treatment increased the level of insulin degradation enzyme (IDE) and neprilysin (NEP) and decreased the level of β-site app cleaving enzyme 1(BACE1) in the brain of APP/PS1 mice. BJJS-treated APP/PS1 mice appeared to have reductions of Aβ deposition and senile plaques, and showed higher levels of neurotrophic factors in the brain. We also found that BJJS had an inhibitory function on neuroinflammation in APP/PS1 mice. In addition, the synapse structure relevant proteins were elevated in the brain of BJJS-treated APP/PS1 mice. The present results indicated that BJJS could attenuate cognitive impairment via ameliorating the AD-related pathological alterations in APP/PS1 mice. These findings suggest that BJJS may be a potential therapeutic strategy in Alzheimer's disease.

Highlights

As we know, Alzheimer’s disease (AD) is the most common dementia among the aged population
The result revealed that the crossing times of the platform location and the time spent in the target quadrant or in the opposite quadrant significantly differed among the 4 experimental groups (Figure 1B, 1C, 1D)
We demonstrated that BJJS treatment improved the learning and memory abilities and attenuated the progress of Alzheimer's disease (AD)-associated neuropathological markers in amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mice

Summary

Introduction

Alzheimer’s disease (AD) is the most common dementia among the aged population. Memory impairment and progressive cognitive dysfunction are the most representative symptoms of AD [1]. The pathological hallmarks of AD by the presence of extracellular senile plaques composed of accumulation and aggregation of amyloid-β (Aβ) peptide, intraneuronal neurofibrillary tangles (NFTs), and chronic neuroinflammation [2]. Numerous studies have focused on the neurotoxicity of Aβ since they were identified in senile plaques from AD patients decades ago [3, 4]. Aβ peptides are derived from the sequential proteolysis of the amyloid precursor protein (APP), a single-pass transmembrane glycoprotein with a large extracellular domain. The amyloidogenic processing of APP is mainly catalyzed by β-site app cleaving enzyme 1 (BACE1), the canonical β-secretase

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