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Konopka, W.* ; Kiryk, A.* ; Novak, M.* ; Herwerth, M.* ; Parkitna, J.R.* ; Wawrzyniak, M.* ; Kowarsch, A. ; Michaluk, P.* ; Dzwonek, J.* ; Arnsperger, T.* ; Wilczynski, G.* ; Merkenschlager, M.* ; Theis, F.J. ; Köhr, G.* ; Kaczmarek, L.* ; Schütz, G.*

MicroRNA loss enhances learning and memory in mice.

J. Neurosci. 30, 14835-14842 (2010)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Dicer-dependent noncoding RNAs, including microRNAs (miRNAs), play an important role in a modulation of translation of mRNA transcripts necessary for differentiation in many cell types. In vivo experiments using cell type-specific Dicer1 gene inactivation in neurons showed its essential role for neuronal development and survival. However, little is known about the consequences of a loss of miRNAs in adult, fully differentiated neurons. To address this question, we used an inducible variant of the Cre recombinase (tamoxifen-inducible CreERT2) under control of Camk2a gene regulatory elements. After induction of Dicer1 gene deletion in adult mouse forebrain, we observed a progressive loss of a whole set of brain-specific miRNAs. Animals were tested in a battery of both aversively and appetitively motivated cognitive tasks, such as Morris water maze, IntelliCage system, or trace fear conditioning. Compatible with rather long half-life of miRNAs in hippocampal neurons, we observed an enhancement of memory strength of mutant mice 12 weeks after the Dicer1 gene mutation, before the onset of neurodegenerative process. In acute brain slices, immediately after high-frequency stimulation of the Schaffer collaterals, the efficacy at CA3-to-CA1 synapses was higher in mutant than in control mice, whereas long-term potentiation was comparable between genotypes. This phenotype was reflected at the subcellular and molecular level by the elongated filopodia-like shaped dendritic spines and an increased translation of synaptic plasticity-related proteins, such as BDNF and MMP-9 in mutant animals. The presented work shows miRNAs as key players in the learning and memory process of mammals.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Long-term potentiation; dendritic spine morphogenesis; synaptic plasticity; protein-synthesis; Messenger-RNÀ; Matrix-metalloproteinase-9; Neurons; Dicer; Absence; Neurodegeneration
Language english
Publication Year 2010
HGF-reported in Year 2010
ISSN (print) / ISBN 0270-6474
e-ISSN 1529-2401
Journal Journal of Neuroscience
Quellenangaben Volume: 30, Issue: 44, Pages: 14835-14842 Article Number: , Supplement: ,
Publisher Society for Neuroscience
Reviewing status Peer reviewed
Institute(s) Institute of Bioinformatics and Systems Biology (IBIS)
POF-Topic(s) 30505 - New Technologies for Biomedical Discoveries
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503700-001
PubMed ID 21048142
DOI 10.1523/JNEUROSCI.3030-10.2010
Scopus ID 78049520499
Erfassungsdatum 2010-12-31
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