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Molecular Neurobiology

, Volume 55, Issue 6, pp 5232–5242 | Cite as

MicroRNA Profiling in Aging Brain of PSEN1/PSEN2 Double Knockout Mice

  • Suji Ham
  • Tae Kyoo Kim
  • Sangjoon Lee
  • Ya-Ping Tang
  • Heh-In Im
Article

Abstract

MicroRNAs are small non-coding RNAs that function as regulators of gene expression. The altered expression of microRNAs influences the pathogenesis of Alzheimer’s disease. Many researchers have focused on studies based on the relatively distinctive etiology of familial Alzheimer’s disease due to the absence of risk factors in the pathogenesis of sporadic Alzheimer’s disease. Although there is a limitation in Alzheimer’s disease studies, both Alzheimer’s disease types have a common risk factor—aging. No study to date has examined the aging factor in Alzheimer’s disease animal models with microRNAs. To investigate the effect of aging on the changes in microRNA expressions in the Alzheimer’s disease animal model, we selected 37 hippocampal microRNAs whose expression in 12- and 18-month aged mice changed significantly using microRNA microarray. On the basis of bioinformatics databases, 30 hippocampal microRNAs and their putative targets of PSEN1/PSEN2 double knockout mice were included in 28 pathways such as the wnt signaling pathway and ubiquitin-mediated proteolysis pathway. Cortical microRNAs and its putative targets involved in pathological aging were included in only four pathways such as the heparin sulfate biosynthesis. The altered expressions of these hippocampal microRNAs were associated to the imbalance between neurotoxic and neuroprotective functions and seemed to affect neurodegeneration in PSEN1/PSEN2 double knockout mice more severely than in wild-type mice. This microRNA profiling suggests that microRNAs play potential roles in the normal aging process, as well as in the Alzheimer’s disease process.

Keywords

MicroRNA PSEN dKO mouse Alzheimer’s disease Aging Microarray Neurodegeneration 

Abbreviations

AD

Alzheimer’s diseases

APP

Amyloid precursor protein

DAVID

Database for annotation, visualization, and integrated discovery

SAD

Sporadic Alzheimer’s disease

FAD

Familial Alzheimer’s disease

KEGG

Kyoto Encyclopedia of Genes and Genomes

mRNA

Messenger RNA

MiRNA

microRNA

TGF

Transforming growth factor

PSEN dKO

PSEN1/PSEN2 conditional double knockout

WT

Wild type

XIAP

X-linked inhibitor of apoptosis

BID

BH3 interacting domain death agonist

PS

Presenilins

Notes

Acknowledgements

This research was funded by the National Research Council of Science & Technology (NST) grant by the Korean government (MSIP) (No. CRC-15-04-KIST).

Authors’ Contributions

H-II and Y-PT designed the study. H-II carried out the RNA isolation and microarray, and reviewed and commented on the manuscript. SH analyzed, interpreted data, and drafted the manuscript. SL interpreted data and helped in drafting the manuscript. Y-PT helped to design and review the study. TK discussed and edited the manuscript for submission. All authors read and approved the final manuscript.

Compliance with Ethical Standards

All procedures regarding the use and handling of mice were conducted as approved by the Institutional Animal Care and Use Committee (IACUC) of the Korea Institute of Science and Technology.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Convergence Research Center for Diagnosis, Treatment and Care System of DementiaKorea Institute of Science and Technology (KIST)SeoulRepublic of Korea
  2. 2.Division of Bio-Medical Science &Technology, KIST SchoolKorea University of Science and TechnologySeoulRepublic of Korea
  3. 3.Department of BiologyBoston UniversityBostonUSA
  4. 4.Center for Neuroscience, Brain Science InstituteKorea Institute of Science and Technology (KIST)SeoulRepublic of Korea
  5. 5.Neuroscience Center of ExcellenceLouisiana State University Health New Orleans Sciences CenterNew OrleansUSA

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