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miR‐204 downregulates EphB2 in aging mouse hippocampal neurons

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 firs...

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Autores principales: Danka Mohammed, Chand Parvez, Rhee, Hwanseok, Phee, Bong‐Kwan, Kim, Kunhyung, Kim, Hee‐Jin, Lee, Hyehyeon, Park, Jung Hoon, Jung, Jung Hee, Kim, Jeong Yeon, Kim, Hyoung‐Chin, Park, Sang Ki, Nam, Hong Gil, Kim, Keetae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783348/
https://www.ncbi.nlm.nih.gov/pubmed/26799631
http://dx.doi.org/10.1111/acel.12444
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author Danka Mohammed, Chand Parvez
Rhee, Hwanseok
Phee, Bong‐Kwan
Kim, Kunhyung
Kim, Hee‐Jin
Lee, Hyehyeon
Park, Jung Hoon
Jung, Jung Hee
Kim, Jeong Yeon
Kim, Hyoung‐Chin
Park, Sang Ki
Nam, Hong Gil
Kim, Keetae
author_facet Danka Mohammed, Chand Parvez
Rhee, Hwanseok
Phee, Bong‐Kwan
Kim, Kunhyung
Kim, Hee‐Jin
Lee, Hyehyeon
Park, Jung Hoon
Jung, Jung Hee
Kim, Jeong Yeon
Kim, Hyoung‐Chin
Park, Sang Ki
Nam, Hong Gil
Kim, Keetae
author_sort Danka Mohammed, Chand Parvez
collection PubMed
description 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.
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spelling pubmed-47833482016-04-13 miR‐204 downregulates EphB2 in aging mouse hippocampal neurons Danka Mohammed, Chand Parvez Rhee, Hwanseok Phee, Bong‐Kwan Kim, Kunhyung Kim, Hee‐Jin Lee, Hyehyeon Park, Jung Hoon Jung, Jung Hee Kim, Jeong Yeon Kim, Hyoung‐Chin Park, Sang Ki Nam, Hong Gil Kim, Keetae Aging Cell Original Articles 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. John Wiley and Sons Inc. 2016-01-22 2016-04 /pmc/articles/PMC4783348/ /pubmed/26799631 http://dx.doi.org/10.1111/acel.12444 Text en © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Danka Mohammed, Chand Parvez
Rhee, Hwanseok
Phee, Bong‐Kwan
Kim, Kunhyung
Kim, Hee‐Jin
Lee, Hyehyeon
Park, Jung Hoon
Jung, Jung Hee
Kim, Jeong Yeon
Kim, Hyoung‐Chin
Park, Sang Ki
Nam, Hong Gil
Kim, Keetae
miR‐204 downregulates EphB2 in aging mouse hippocampal neurons
title miR‐204 downregulates EphB2 in aging mouse hippocampal neurons
title_full miR‐204 downregulates EphB2 in aging mouse hippocampal neurons
title_fullStr miR‐204 downregulates EphB2 in aging mouse hippocampal neurons
title_full_unstemmed miR‐204 downregulates EphB2 in aging mouse hippocampal neurons
title_short miR‐204 downregulates EphB2 in aging mouse hippocampal neurons
title_sort mir‐204 downregulates ephb2 in aging mouse hippocampal neurons
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783348/
https://www.ncbi.nlm.nih.gov/pubmed/26799631
http://dx.doi.org/10.1111/acel.12444
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