Cinnamomum verum-derived O-methoxycinnamaldehyde prevents lipopolysaccharide-induced depressive-like behavior in mice via NFAT mRNA stability in T lymphocytes

Abstract

BackgroundDepressive-like behaviors are related to inflammatory immune activation. Cinnamomum verum (CV) has anti-inflammatory effects, but the molecular mechanisms underlying the antidepressant effects after immunological activation still remain elusive. PurposeThe aim of the present study was to investigate the effect of CV in improving depressive-like behavior and explore its underlying mechanism in T lymphocytes. MethodsMice were randomly divided into Control, LPS, LPS plus fluoxetine, LPS plus CV, and LPS plus MCA groups. Behavior was evaluated using forced swimming test (FST) and tail suspension test (TST). The experimental group mice were exposed to LPS to induce depressive-like behavior. Cell viability was measured upon treating splenic T lymphocytes and Jurkat T cells with CV. Cytokine activity was measured using ELISA and RT-qPCR. The components of CV were analyzed by HPLC. NFAT expression was evaluated by western blotting, immunofluorescence, and luciferase assay. To verify the half-life of NFAT mRNA, Jurkat cells were treated with actinomycin D for 1.5, 3, and 4.5 h. ResultsCV effectively prevents inflammation-induced depressive-like behaviors. CV dose-dependently decreased protein and mRNA levels of TNFα and IL-2. Inhibition of TNFα and IL-2 production involves an MCA-mediated decrease in NFAT mRNA level, rather than inhibition of nuclear translocation. This mechanism was independent of NFAT transcription inducer p38 MAPK; it can be attributed to the promotion of NFAT mRNA decay. ConclusionOverall, MCA might be an alternative or adjuvant to existing NFAT-targeting immunosuppressants for clinical prophylaxis or therapy in the context of inflammation-induced depressive disorder or other T-cell-associated inflammatory disorders.