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          Institute: MPI für medizinische Forschung     Collection: Abteilung Molekulare Neurobiologie     Display Documents

ID: 545962.0, MPI für medizinische Forschung / Abteilung Molekulare Neurobiologie
MicroRNA loss enhances learning and memory in mice
Translation of Title:MicroRNA loss enhances learning and memory in mice
Authors:Konopka, Witold; Kiryk, Anna; Novak, Martin; Herwerth, Marina; Parkitna, Jan Rodriguez; Wawrzyniak, Marcin; Kowarsch, Andreas; Michaluk, Piotr; Dzwonek, Joanna; Arnsperger, Tabea; Wilczynski, Grzegorz; Merkenschlager, Matthias; Theis, Fabian J.; Köhr, Georg; Kaczmarek, Leszek; Schütz, Günther
Date of Publication (YYYY-MM-DD):2010-11-03
Title of Journal:Journal of Neuroscience
Journal Abbrev.:J. Neurosci.
Issue / Number:44
Start Page:14835
End Page:14842
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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 (tamoxifeninducible
CreERT2) under control of Camk2a gene regulatory elements. After induction of Dicer1 gene deletion in adult mouse forebrain,
weobserved 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 asBDNFandMMP−9in mutant animals.
The presented work shows miRNAs as key players in the learning and memory process of mammals.
Last Change of the Resource (YYYY-MM-DD):--
External Publication Status:published
Document Type:Article
Communicated by:Wulf Kaiser
Affiliations:MPI für medizinische Forschung/Abteilung Molekulare Neurobiologie
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