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miR-204 downregulates EphB2 in aging mouse hippocampal neurons

Title
miR-204 downregulates EphB2 in aging mouse hippocampal neurons
Authors
Mohammed, Chand Parvez DankaRhee, HwanseokPhee, Bong-KwanKim, KunhyungKim, Hee-JinLee, HyehyeonPark, Jung HoonJung, Hee JungKim, Jeong YeonKim, Hyoung-ChinPark, Sang KiNam, Hong GilKim, Keetae
DGIST Authors
Nam, Hong Gil
Issue Date
2016-04
Citation
Aging Cell, 15(2), 380-388
Type
Article
Article Type
Article
Keywords
AgedAgingAnimal CellAnimal TissueBrain Nerve CellCell AgingCell SurfaceControlled StudyDown-RegulationEphB2Ephrin A1Ephrin B2Ephrin Receptor B2Gene ExpressionGenetic TransfectionGroups by AgeHippocampal TissueHippocampusMaleMicroRNAMicroRNA-204MiRNA204MouseN Methyl Dextro Aspartic Acid Receptor 1NMDA ReceptorNon-HumanPhenotypePriority JournalProtein ExpressionProtein P16RhoA Guanine Nucleotide Binding ProteinTranscriptomeUnclassified DrugUpregulation
ISSN
1474-9718
Abstract
Hippocampal synaptic function and plasticity deteriorate with age, often resulting in learning and memory deficits. As MicroRNAs (miRNAs) are important regulators of neuronal protein expression, we examined whether miRNAs may contribute to this age-associated decline in hippocampal function. We first compared the small RNA transcriptome of hippocampal tissues from young and old mice. Among 269 hippocampal miRNAs, 80 were differentially expressed (≥ ;twofold) among the age groups. We focused on 36 miRNAs upregulated in the old mice compared with those in the young mice. The potential targets of these 36 miRNAs included 11 critical Eph/Ephrin synaptic signaling components. The expression levels of several genes in the Eph/Ephrin pathway, including EphB2, were significantly downregulated in the aged hippocampus. EphB2 is a known regulator of synaptic plasticity in hippocampal neurons, in part by regulating the surface expression of the NMDA receptor NR1 subunit. We found that EphB2 is a direct target of miR-204 among miRNAs that were upregulated with age. The transfection of primary hippocampal neurons with a miR-204 mimic suppressed both EphB2 mRNA and protein expression and reduced the surface expression of NR1. Transfection of miR-204 also decreased the total expression of NR1. miR-204 induces senescence-like phenotype in fully matured neurons as evidenced by an increase in p16-positive cells. We suggest that aging is accompanied by the upregulation of miR-204 in the hippocampus, which downregulates EphB2 and results in reduced surface and total NR1 expression. This mechanism may contribute to age-associated decline in hippocampal synaptic plasticity and the related cognitive functions. © 2016 The Anatomical Society and John Wiley & Sons Ltd.
URI
http://hdl.handle.net/20.500.11750/5109
DOI
10.1111/acel.12444
Publisher
Wiley Blackwell
Related Researcher
  • Author Nam, Hong Gil CBRG(Complex Biology Research Group)
  • Research Interests Plant Aging and Life History; Systems Biology; Complexbiology; Comparative Aging Research
Files:
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Collection:
Department of New BiologyCBRG(Complex Biology Research Group)1. Journal Articles


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