Malmevik Josephine, Petri Rebecca, Knauff Pina, Brattås Per Ludvik, Åkerblom Malin, Jakobsson Johan
Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, Sölvegatan 17, 221 84 Lund, Sweden.
Sci Rep. 2016 Jan 27;6:19879. doi: 10.1038/srep19879.
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.
微小RNA（miRNA）是介导基因表达转录后调控的小的非编码RNA。miRNA最近被认为与海马体依赖的功能有关，如学习和记忆，尽管单个miRNA在这些过程中的作用仍 largely未知。在这里，我们使用腺相关病毒（AAV）传递的单个、高表达且脑富集的miRNA海绵体，即miR-124、miR-9和miR-34，在海马神经元中实现了稳定抑制。分子和认知研究揭示了miR-124在学习和记忆中的作用。抑制miR-124导致空间学习和工作记忆能力增强，这可能是通过改变与突触可塑性和神经元传递相关的基因水平实现的。相比之下，抑制miR-9或miR-34分别导致空间学习能力和参考记忆能力下降。在分子水平上，抑制miR-9导致与细胞黏附、内吞作用和细胞死亡相关的基因表达改变，而抑制miR-34导致与神经活性配体-受体转导和细胞通讯相关的转录组变化。总之，这项研究确立了单个miRNA在海马体功能中的不同作用。
