title: Anxiolytic-like effect of trans-2-decenoic acid ethyl ester in stress-induced anxiety-like model mice.
abstract: Brain-derived neurotrophic factor (BDNF) is considered to be involved in the etiology and treatment of stress-related mood disorders including anxiety. However, application of BDNF itself has many technical and pharmacological problems such as instability and/or a lack of appropriate delivery systems. To overcome these, we developed trans-2-decenoic acid ethyl ester (DAEE) as a stable and small molecule with BDNF-like activities. In the present study, we tested the activities of DAEE on a stress-induced anxiety-like mouse model. Mice were kept in cages and subjected to 3 sets of sequential leaning, drenching, and rotation as chronic mild stresses applied for 1-2 days over a 3-week period; and the anxiety-like symptom (reduced time spent in open arm of the maze) was evaluated by use of the elevated plus-maze test. A daily intraperitoneal administration of DAEE competed against the expression of the anxiety-like symptom when administered during the stress-loading period, and became therapeutic when administered after the stress-loading. This activity was accompanied by amelioration of the stress-induced reduction in the levels of BDNF and neurotrophin-3 mRNAs and phosphorylated extracellular signal-regulated kinases (ERK) 1/2 in the hippocampus. These results demonstrated that DAEE behaved like an anxiolytic and ameliorated this characteristic anxiety-like symptom, suggesting that DAEE may be a promising candidate for a novel anxiolytic with a new mechanism of action.
authors.affiliation: Laboratory of Molecular Biology, Department of Biofunctional Analysis, Gifu Pharmaceutical University, Daigaku-nishi 1-25-4, Gifu 501-1196, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Makino
authors.forename: Munekazu
authors.initials: M
authors.lastname: Iinuma
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Fukumitsu
authors.forename: Hitomi
authors.initials: H
authors.lastname: Soumiya
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Shoei
authors.initials: S
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology*; D004195:Disease Models, Animal; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D013315:Stress, Psychological
chemical_list: D005229:Fatty Acids, Monounsaturated; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C052476:2-decenoic acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3