title: Overexpression of 12/15-lipoxygenase increases anxiety behavior in female mice.
abstract: The 12/15-lipoxygenase (12/15-LO) is an enzyme widely distributed in the central nervous system, and it has been involved in the neurobiology of Alzheimer's disease. However, whether this pathway is also involved in neuropsychiatry disorders including anxiety remain to be investigated. In this study we investigated whether genetic over-expression of 12/15-LO (H12/15-LO) modulates some elevated plus maze and Y-maze behaviors. While we observed that H12/15LO mice at the age of 12 months did not differ from wild type in the elevated plus maze paradigm, when they reached the age of 15 months, they manifested an increased anxiety-like behavior compared with controls. By contrast, no differences between the 2 groups at both ages when they were tested for working memory in the Y-maze paradigm. Additionally, we found that the change in anxiety was associated with a reduction in phosphorylation of the transcription factor CREB (cAMP response element-binding protein), and a significant increase in the synaptic protein synaptophysin. Taken together our findings suggest a novel role for 12/15-LO in the pathogenesis of anxiety-like behavior.
authors.affiliation: Department of Pharmacology, Center for Translational Medicine, Temple University, School of Medicine, Philadelphia, PA, USA.
authors.forename: Yash B
authors.initials: YB
authors.lastname: Joshi
authors.affiliation: Department of Pharmacology, Center for Translational Medicine, Temple University, School of Medicine, Philadelphia, PA, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Meco
authors.affiliation: Department of Pharmacology, Center for Translational Medicine, Temple University, School of Medicine, Philadelphia, PA, USA. Electronic address: praticod@temple.edu.
authors.forename: Domenico
authors.initials: D
authors.lastname: Praticò
mesh_terms: D000375:Aging / Q000235:genetics / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000201:enzymology* / Q000235:genetics*; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D008568:Memory / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D010766:Phosphorylation; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D016708:Synaptophysin; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase
keywords: 12/15-lipoxygenase; Anxiety; Behavior; CREB