title: Expression of amyloid-associated miRNAs in both the forebrain cortex and hippocampus of middle-aged rat.
abstract: 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 (Aβ) peptide following the abnormal proteolytic processing of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin, Heilongjiang Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Che
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Sun
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Niu
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Su
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Bao
authors.forename: Zidong Donna
authors.initials: ZD
authors.lastname: Fu
authors.forename: Huai-Lei
authors.initials: HL
authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Hou
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Ai
mesh_terms: D000375:Aging / Q000235:genetics*; D000682:Amyloid / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D003071:Cognition; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D035683:MicroRNAs; D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat