microRNAs miR-124, let-7d and miR-181a regulate cocaine-induced plasticity
- Chandrasekar, Vijay Division of Biochemistry, Department of Medicine, University of Fribourg, Switzerland
- Dreyer, Jean-Luc Division of Biochemistry, Department of Medicine, University of Fribourg, Switzerland
-
22.08.2009
Published in:
- Molecular and Cellular Neuroscience. - 2009, vol. 42, no. 4, p. 350-362
English
MicroRNAs play key regulatory roles in cellular processes including neurogenesis, synapse development and plasticity in the brain. Psychostimulants induces strong neuroadaptive changes through a surfeit of gene regulatory mechanisms leading to addiction. MicroRNA profiling for identifying miRNAs regulating cocaine-induced, plasticity-related genes revealed significant regulation of a set of miRNAs upon cocaine administration, especially let-7d, miR-181a and the brain-specific miR-124. These miRNAs target many genes involved in cocaine addiction. Precursor and mature miRNA quantification by qRT-PCR showed that miR-124 and let-7d are significantly downregulated, whereas miR-181a is induced in the mesolimbic dopaminergic system under chronic cocaine administration. Results were confirmed by in situ hybridization, Northern blots, FISH analysis and RNase protection assay. Using lentiviral-mediated miRNA expression, we show a significant downregulation of BDNF and D3R both at mRNA and protein levels by miR-124 and let-7d, respectively. Our data suggest that miR-124, let-7d and miR-181a may be involved in a complex feedback loop with cocaine-responsive plasticity genes, highlighting the possibility that some miRNAs are key regulators of the reward circuit and may be implicated in addiction.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Médecine
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
-
- RERO DOC 17043
- DOI 10.1016/j.mcn.2009.08.009
- Persistent URL
- https://folia.unifr.ch/unifr/documents/301417
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