Expression of Amyloid-Associated miRNAs in Both the Forebrain Cortex and Hippocampus of Middle-Aged Rat

被引：33

作者：

Che, Hui ^{[1
]}

Sun, Li-Hua ^{[1
]}

Guo, Fei ^{[1
]}

Niu, Hui-Fang ^{[1
]}

Su, Xiao-Lin ^{[1
]}

Bao, Ya-Nan ^{[1
]}

Fu, Zidong Donna ^{[1
]}

Liu, Huai-Lei ^{[2
]}

Hou, Xu ^{[2
]}

Yang, Bao-Feng ^{[1
]}

Ai, Jing ^{[1
]}

机构：

[1] Harbin Med Univ, Dept Pharmacol, State Prov Key Labs Biomed Pharmaceut China, Harbin 150081, Heilongjiang Pr, Peoples R China

[2] Harbin Med Univ, Affiliated Hosp 1, Dept Neurosurg, Harbin 150081, Heilongjiang Pr, Peoples R China

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2014年 / 33卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Aging; microRNAs; APP; BACE1; Learning; Memory; MESSENGER-RNA DEGRADATION; PRECURSOR PROTEIN APP; ALZHEIMERS-DISEASE; BETA-SECRETASE; COGNITIVE DECLINE; A-BETA; BRAIN; MICRORNA; MEMORY; BACE1;

D O I：

10.1159/000356646

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background: Aging is associated with the gradual cognitive decline and shows the typical senile plaque formation in the brain, which results from the aggregation of beta amyloid (A beta) peptide following the abnormal proteolytic processing of amyloid precursor protein (APP) by beta-secretase (BACE1) and gamma-secretase. Accumulating evidence indicates that several microRNAs (miRNAs) are involved in the Alzheimer's disease (AD) by regulating the expression of APP and BACE1 proteins. However, the cognitive ability and the expression profile of the APP- and BACE1-associated miRNAs in the middle-aged population are largely unknown. Methods: The learning and memory ability in rats were determined by Morris Water Maze test. The protein levels of APP and BACE1 were detected by western blotting. The quantitative polymerase chain reaction was used to identify the miRNAs levels in forebrain cortex and the hippocampus. Results: Middle-aged rats have declined learning ability without changes in the memory ability, and increased APP and BACE1 protein expression in the forebrain cortex. Computational analysis using Targetscan and Pictar databases reveals that totally 4 predicted miRNAs have conserved binding site with APP, namely miR-106b, -17-5p, -153, -101. All of them showed decreased expression in both the forebrain cortex and hippocampus. Among the 10 predicted miRNAs targeting BACE1, different expression profiles were identified in the forebrain cortex (decreased: miR-9, -19a, -135a, -15b, -16, -195, -29c, -214; increased: miR-124; no change: miR-141) and the hippocampus (decreased: miR-9, -15b, -16, -195, -29c, -124; increased: miR-19a, -135a, -214, -141) in the middle-aged rats compared with the young rats. Conclusion: Our results provided the first evidence that middle-aged rats have begun displaying cognitive disability with abnormal expression of APP- and BACE1-related miRNAs in the hippocampus and forebrain cortex. Copyright (C) 2014 S. Karger AG, Basel

引用

页码：11 / 22

页数：12

共 60 条

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