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Accession IconSRP058347

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

Organism Icon Mus musculus
Sample Icon 12 Downloadable Samples
Technology Badge IconIllumina HiSeq 2000

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Description
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. Overall design: Three RNA samples containing bilateral entire hippocampi from three different mice, per group. Group 1 were injected with vector containing GFP and a miR34sp/miR9sp and the other group were subjected to a vector expressing GFP only.
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12
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