MicroRNA Profiling in Aging Brain of PSEN1/PSEN2 Double Knockout Mice
- 722 Downloads
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.
KeywordsMicroRNA PSEN dKO mouse Alzheimer’s disease Aging Microarray Neurodegeneration
Amyloid precursor protein
Database for annotation, visualization, and integrated discovery
Sporadic Alzheimer’s disease
Familial Alzheimer’s disease
Kyoto Encyclopedia of Genes and Genomes
Transforming growth factor
- PSEN dKO
PSEN1/PSEN2 conditional double knockout
X-linked inhibitor of apoptosis
BH3 interacting domain death agonist
This research was funded by the National Research Council of Science & Technology (NST) grant by the Korean government (MSIP) (No. CRC-15-04-KIST).
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.
- 2.Yan K, Jianban W, Liudi Y (2014) MicroRNA expression analysis of adult-onset drosophila Alzheimer’s disease model. Curr Alzheimer Res 11(9):882–891Google Scholar
- 3.Delay C, Hébert SS (2011) MicroRNAs and Alzheimer’s disease mouse models: current insights and future research avenues. International Journal of Alzheimer Disease 2011:6Google Scholar
- 6.Gabrielle, S. What is early onset familial alzheimer disease (eFAD)? ; Available from: http://www.alzforum.org/early-onset-familial-ad/overview/what-early-onset-familial-alzheimer-disease-efad
- 32.von Bernhardi R et al (2015) Role of TGFbeta signaling in the pathogenesis of Alzheimer’s disease. Front Cell Neurosci 9:426Google Scholar
- 40.RF, Z, (2015) Of mice and men and Alzheimer disease: aging versus time. JSM Alzheimer’s Dis Relat Dement 2(2):1017Google Scholar
- 41.Age converter. Available from: http://www.age-converter.com/mouse-age-calculator. Accessed 13 July 2016
- 42.Life span as a biomarker. Available from: https://www.jax.org/research-and-faculty/research-labs/the-harrison-lab/gerontology/life-span-as-a-biomarker. Accessed 13 July 2016