Satb2 determines miRNA expression and long-term memory in the adult central nervous system
| Autor: | Andreas Abentung, Nigel Whittle, Georg Dechant, Andre Fischer, Nicolas Singewald, Dietmar Rieder, Gaurav Jain, Chethan Reddy, Martin Korte, Galina Apostolova, Isabella Cera, Farahnaz Sananbenesi, Clemens Jaitner, Andrea Delekate |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Mouse biosynthesis [MicroRNAs] physiology [Hippocampus] Nonsynaptic plasticity Hippocampus Gene Knockout Techniques Mice 0302 clinical medicine metabolism [Transcription Factors] Biology (General) Neuronal memory allocation Mice Knockout SATB2 protein mouse Long-term memory General Neuroscience genetics [Matrix Attachment Region Binding Proteins] Long-term potentiation General Medicine Anatomy genetics [Transcription Factors] Genes and Chromosomes Medicine Memory consolidation LTP Research Article Memory Long-Term QH301-705.5 Science Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences long-term memory Metaplasticity Animals miRNA synaptic plasticity General Immunology and Microbiology Matrix Attachment Region Binding Proteins Satb2 adult central nervous system MicroRNAs 030104 developmental biology Gene Expression Regulation metabolism [Matrix Attachment Region Binding Proteins] Synaptic plasticity Forebrain chromatin Neuroscience ddc:600 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | eLife 5, e17361 (2016). doi:10.7554/eLife.17361 eLife, Vol 5 (2016) eLife |
| Popis: | SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory. DOI: http://dx.doi.org/10.7554/eLife.17361.001 |
| Databáze: | OpenAIRE |
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