title: Acute stress alters amygdala microRNA miR-135a and miR-124 expression: inferences for corticosteroid dependent stress response.
abstract: The amygdala is a brain structure considered a key node for the regulation of neuroendocrine stress response. Stress-induced response in amygdala is accomplished through neurotransmitter activation and an alteration of gene expression. MicroRNAs (miRNAs) are important regulators of gene expression in the nervous system and are very well suited effectors of stress response for their ability to reversibly silence specific mRNAs. In order to study how acute stress affects miRNAs expression in amygdala we analyzed the miRNA profile after two hours of mouse restraint, by microarray analysis and reverse transcription real time PCR. We found that miR-135a and miR-124 were negatively regulated. Among in silico predicted targets we identified the mineralocorticoid receptor (MR) as a target of both miR-135a and miR-124. Luciferase experiments and endogenous protein expression analysis upon miRNA upregulation and inhibition allowed us to demonstrate that mir-135a and mir-124 are able to negatively affect the expression of the MR. The increased levels of the amygdala MR protein after two hours of restraint, that we analyzed by western blot, negatively correlate with miR-135a and miR-124 expression. These findings point to a role of miR-135a and miR-124 in acute stress as regulators of the MR, an important effector of early stress response.
authors.affiliation: Institute of Cellular Biology and Neurobiology, Consiglio Nazionale delle Ricerche, A. Buzzati-Traverso Campus, Monterotondo, Rome, Italy ; Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Mannironi
authors.forename: Jeremy
authors.initials: J
authors.lastname: Camon
authors.forename: Francesca
authors.initials: F
authors.lastname: De Vito
authors.forename: Antonio
authors.initials: A
authors.lastname: Biundo
authors.forename: Maria Egle
authors.initials: ME
authors.lastname: De Stefano
authors.forename: Irene
authors.initials: I
authors.lastname: Persiconi
authors.forename: Irene
authors.initials: I
authors.lastname: Bozzoni
authors.forename: Paola
authors.initials: P
authors.lastname: Fragapane
authors.forename: Andrea
authors.initials: A
authors.lastname: Mele
authors.forename: Carlo
authors.initials: C
authors.lastname: Presutti
mesh_terms: D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000305:Adrenal Cortex Hormones; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; C549289:Mirn135 microRNA, mouse; D018161:Receptors, Mineralocorticoid
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