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Distinct cognitive effects and underlying transcriptome changes upon inhibition of individual miRNAs in hippocampal neurons.

Malmevik, Josephine LU ; Petri, Rebecca LU ; Knauff, Pina LU ; Brattaas, Per Ludvik LU ; Åkerblom, Malin LU and Jakobsson, Johan LU (2016) In Scientific Reports 6.
Abstract
MicroRNAs (miRNA) are small, non-coding RNAs mediating post-transcriptional regulation of gene expression. miRNAs have recently been implicated in hippocampus-dependent functions such as learning and memory, although the roles of individual miRNAs in these processes remain largely unknown. Here, we achieved stable inhibition using AAV-delivered miRNA sponges of individual, highly expressed and brain-enriched miRNAs; miR-124, miR-9 and miR-34, in hippocampal neurons. Molecular and cognitive studies revealed a role for miR-124 in learning and memory. Inhibition of miR-124 resulted in an enhanced spatial learning and working memory capacity, potentially through altered levels of genes linked to synaptic plasticity and neuronal transmission.... (More)
MicroRNAs (miRNA) are small, non-coding RNAs mediating post-transcriptional regulation of gene expression. miRNAs have recently been implicated in hippocampus-dependent functions such as learning and memory, although the roles of individual miRNAs in these processes remain largely unknown. Here, we achieved stable inhibition using AAV-delivered miRNA sponges of individual, highly expressed and brain-enriched miRNAs; miR-124, miR-9 and miR-34, in hippocampal neurons. Molecular and cognitive studies revealed a role for miR-124 in learning and memory. Inhibition of miR-124 resulted in an enhanced spatial learning and working memory capacity, potentially through altered levels of genes linked to synaptic plasticity and neuronal transmission. In contrast, inhibition of miR-9 or miR-34 led to a decreased capacity of spatial learning and of reference memory, respectively. On a molecular level, miR-9 inhibition resulted in altered expression of genes related to cell adhesion, endocytosis and cell death, while miR-34 inhibition caused transcriptome changes linked to neuroactive ligand-receptor transduction and cell communication. In summary, this study establishes distinct roles for individual miRNAs in hippocampal function. (Less)
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published
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in
Scientific Reports
volume
6
publisher
Nature Publishing Group
external identifiers
  • pmid:26813637
  • wos:000368669800001
  • scopus:84955517818
ISSN
2045-2322
DOI
10.1038/srep19879
language
English
LU publication?
yes
id
aca7100f-004b-44cd-a264-71e18a206f93 (old id 8573571)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26813637?dopt=Abstract
date added to LUP
2016-02-05 23:57:29
date last changed
2017-09-24 04:04:42
@article{aca7100f-004b-44cd-a264-71e18a206f93,
  abstract     = {MicroRNAs (miRNA) are small, non-coding RNAs mediating post-transcriptional regulation of gene expression. miRNAs have recently been implicated in hippocampus-dependent functions such as learning and memory, although the roles of individual miRNAs in these processes remain largely unknown. Here, we achieved stable inhibition using AAV-delivered miRNA sponges of individual, highly expressed and brain-enriched miRNAs; miR-124, miR-9 and miR-34, in hippocampal neurons. Molecular and cognitive studies revealed a role for miR-124 in learning and memory. Inhibition of miR-124 resulted in an enhanced spatial learning and working memory capacity, potentially through altered levels of genes linked to synaptic plasticity and neuronal transmission. In contrast, inhibition of miR-9 or miR-34 led to a decreased capacity of spatial learning and of reference memory, respectively. On a molecular level, miR-9 inhibition resulted in altered expression of genes related to cell adhesion, endocytosis and cell death, while miR-34 inhibition caused transcriptome changes linked to neuroactive ligand-receptor transduction and cell communication. In summary, this study establishes distinct roles for individual miRNAs in hippocampal function.},
  articleno    = {19879},
  author       = {Malmevik, Josephine and Petri, Rebecca and Knauff, Pina and Brattaas, Per Ludvik and Åkerblom, Malin and Jakobsson, Johan},
  issn         = {2045-2322},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Distinct cognitive effects and underlying transcriptome changes upon inhibition of individual miRNAs in hippocampal neurons.},
  url          = {http://dx.doi.org/10.1038/srep19879},
  volume       = {6},
  year         = {2016},
}