MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction/abstract below Press release from Scripps institute http://www.scripps.edu/news/press/012609.html
Jannet Kocerhaa, Mohammad Ali Faghihia, Miguel A. Lopez-Toledanoa, Jia Huanga,b, Amy J. Ramseyc, Marc G. Caronc, Nicole Salesd, David Willoughbye, Joacim Elmen, Henrik F. Hansen, Henrik Orum, Sakari Kauppinen, Paul J. Kennyh, and Claes Wahlestedt,1 Departments of Molecular and Integrative Neurosciences, Infectology, and Molecular Therapeutics, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458; Departments of Cell Biology and Neurobiology, Duke University Medical Center, Durham, NC 27710; Ocean Ridge Biosciences, 10475 Riverside Drive, Suite 1, Palm Beach Gardens, FL 33410; Santaris Pharma, Horsholm, DK-2970, Denmark; Department of Cellular andMolecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, and Miami Institute for Human Genomics, University of Miami, South Campus, Building C, 12500 SW 152nd Street, Miami, FL 33177
Edited by Floyd E. Bloom, The Scripps Research Institute, La Jolla, CA, and approved December 12, 2008 (received for review June 17, 2008)
N-methyl-D-aspartate (NMDA) glutamate receptors are regulators of fast neurotransmission and synaptic plasticity in the brain. Disruption of NMDA-mediated glutamate signaling has been linked to behavioral deficits displayed in psychiatric disorders such as schizophrenia. Recently, noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators of neuronal functions. Here we show that pharmacological (dizocilpine) or genetic (NR1 hypomorphism) disruption of NMDA receptor signaling reduces levels of a brain-specific miRNA, miR-219, in the prefrontal cortex (PFC) of mice. Consistent with a role for miR-219 in NMDA receptor signaling, we identify calcium/calmodulin dependent protein kinase II subunit (CaMKII), a component of the NMDA receptor signaling cascade, as a target of miR-219. In vivo inhibition of miR-219 by specific antimiR in the murine brain significantly modulated behavioral responses associated with disrupted NMDA receptor transmission. Furthermore, pretreatment with the antipsychotic drugs haloperidol and clozapine preventeddizocilpine-induced effects on miR-219. Taken together, these data support an integral role for miR-219 in the expression of behavioral aberrations associated with NMDA receptor hypofunction. cerebral cortex glutamatergic signaling regulatory RNAEnter Content Here
www.pnas.orgcgidoi10.1073pnas.0805854106