title: MicroRNA-155 deletion reduces anxiety- and depressive-like behaviors in mice.
abstract: Depressive disorders have complex and multi-faceted underlying mechanisms, rendering these disorders difficult to treat consistently and effectively. One under-explored therapeutic strategy for alleviating mood disorders is the targeting of microRNAs (miRs). miRs are small non-coding RNAs that cause sequestration/degradation of specific mRNAs, thereby preventing protein translation and downstream functions. miR-155 has validated and predicted neurotrophic factor and inflammatory mRNA targets, which led to our hypothesis that miR-155 deletion would modulate affective behaviors. To evaluate anxiety-like behavior, wildtype (wt) and miR-155 knockout (ko) mice (littermates; both male and female) were assessed in the open field and on an elevated plus maze. In both tests, miR-155 ko mice spent more time in open areas, suggesting they had reduced anxiety-like behavior. Depressive-like behaviors were assessed using the forced swim test. Compared to wt mice, miR-155 ko mice exhibited reduced float duration and increased latency to float. Further, although all mice exhibited a strong preference for a sucrose solution over water, this preference was enhanced in miR-155 ko mice. miR-155 ko mice had no deficiencies in learning and memory (Barnes maze) or social preference/novelty suggesting that changes in mood were specific. Finally, compared to wt hippocampi, miR-155 ko hippocampi had a reduced inflammatory signature (e.g., decreased IL-6, TNF-a) and female miR-155 ko mice increased ciliary neurotrophic factor expression. Together, these data highlight the importance of studying microRNAs in the context of anxiety and depression and identify miR-155 as a novel potential therapeutic target for improving mood disorders.
authors.affiliation: Department of Neuroscience, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, Columbus, OH 43210, USA. Electronic address: laura.fonken@colorado.edu.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Fonken
authors.affiliation: Department of Neuroscience, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, Columbus, OH 43210, USA; Center for Brain and Spinal Cord Repair, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Gaudet
authors.affiliation: Department of Neuroscience, Columbus, OH 43210, USA.
authors.forename: Kristopher R
authors.initials: KR
authors.lastname: Gaier
authors.affiliation: Department of Neuroscience, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, Columbus, OH 43210, USA.
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Nelson
authors.affiliation: Department of Neuroscience, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, Columbus, OH 43210, USA; Center for Brain and Spinal Cord Repair, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Popovich
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000473:pathology; D001522:Behavior, Animal / Q000502:physiology*; D003863:Depression / Q000235:genetics* / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D019964:Mood Disorders / Q000235:genetics / Q000473:pathology; D009043:Motor Activity / Q000235:genetics
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse
keywords: Cytokine; Depression; Hippocampus; Learning and memory; MicroRNA