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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 orcid (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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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
6
article number
19879
publisher
Nature Publishing Group
external identifiers
  • pmid:26813637
  • wos:000368669800001
  • scopus:84955517818
  • pmid:26813637
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
2016-04-01 14:08:15
date last changed
2022-05-07 21:09:19
@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.}},
  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}},
  doi          = {{10.1038/srep19879}},
  volume       = {{6}},
  year         = {{2016}},
}