Resolvin D1 and D2 Reverse Lipopolysaccharide-Induced Depression-Like Behaviors Through the mTORC1 Signaling Pathway
| Autor: | Kotomi Yoshikawa, Yuka Ishikawa, Kento Shimoda, Masabumi Minami, Satoshi Deyama, Soichiro Ide, Masamichi Satoh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male Docosahexaenoic Acids medicine.drug_class AMPA receptor mTORC1 Pharmacology Mechanistic Target of Rapamycin Complex 1 Statistics Nonparametric 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine medicine Animals Pharmacology (medical) dentate gyrus Regular Research Article Injections Intraventricular resolvin Mice Inbred BALB C Chemistry Dentate gyrus Antagonist Brain Immobility Response Tonic Receptor antagonist Tail suspension test Antidepressive Agents Psychiatry and Mental health Disease Models Animal 030104 developmental biology Hindlimb Suspension depression NBQX Resolvin Oligopeptides 030217 neurology & neurosurgery Locomotion medial prefrontal cortex Signal Transduction |
| Zdroj: | International Journal of Neuropsychopharmacology |
| ISSN: | 1461-1457 |
| Popis: | Background: Resolvin D1 and D2 are bioactive lipid mediators that are generated from docosahexaenoic acid. Although recent preclinical studies suggest that these compounds have antidepressant effects, their mechanisms of action remain unclear. Methods: We investigated mechanisms underlying the antidepressant effects of resolvin D1 and resolvin D2 in lipopolysaccharide (0.8 mg/kg, i.p.)-induced depression model mice using a tail suspension test. Results: I.c.v. infusion of resolvin D1 (10 ng) and resolvin D2 (10 ng) produced antidepressant effects; these effects were significantly blocked by a resolvin D1 receptor antagonist WRW4 (10 µg, i.c.v.) and a resolvin D2 receptor antagonist O-1918 (10 µg, i.c.v.), respectively. The mammalian target of rapamycin complex 1 inhibitor rapamycin (10 mg/kg, i.p.) and a mitogen-activated protein kinase kinase inhibitor U0126 (5 µg, i.c.v.) significantly blocked the antidepressant effects of resolvin D1 and resolvin D2. An AMPA receptor antagonist NBQX (10 mg/kg, i.p.) and a phosphoinositide 3-kinase inhibitor LY294002 (3 µg, i.c.v.) blocked the antidepressant effects of resolvin D1 significantly, but not of resolvin D2. Bilateral infusions of resolvin D1 (0.3 ng/side) or resolvin D2 (0.3 ng/side) into the medial prefrontal cortex or dentate gyrus of the hippocampus produced antidepressant effects. Conclusions: These findings demonstrate that resolvin D1 and resolvin D2 produce antidepressant effects via the mammalian target of rapamycin complex 1 signaling pathway, and that the medial prefrontal cortex and dentate gyrus are important brain regions for these antidepressant effects. These compounds and their receptors may be promising targets for the development of novel rapid-acting antidepressants, like ketamine and scopolamine. |
| Databáze: | OpenAIRE |
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