Effects of caffeic acid on epigenetics in the brain of rats with chronic unpredictable mild stress

Abstract

The present study hypothesized that caffeic acid (3,4-dihydroxycinnamic acid; caa) may exert antidepressant-like effects in rats with chronic unpredictable mild stress via epigenetic mechanisms, such as dna methylation and hydroxymethylation. The chronic unpredictable mild stress (cuMS) model was used to analyze the effects of caa on behavioral phenotypes, and to evaluate the distribution of 5-methylcytosine (5mc) and 5-hydroxymethylcytosine (5hmc) in the hippocampus and prefrontal cortex using immunohistochemistry and immunofluorescence. mrna levels of the genes encoding brain-derived neurotropic factor (BdnF) and catechol-o-methyltransferase (coMT), and key enzymes regulating dna methylation [dna methyltransferase (dnMT)1 and dnMT3a] and hydroxymethylation [Ten-eleven translocation (TeT)1-3] were examined using quantitative (q)Pcr. Furthermore, enrichment of 5mc and 5hmc at the promotor regions of the Bdnf and Comt genes was quantified using chromatin immunoprecipitation-qPcr. Behavioral data showed that caa exerted a slight antidepressant-like effect. Bdnf and Comt genes showed differential expression patterns due to cuMS. caa intervention induced different Dnmt1/Dnmt3a and Tet1/Tet2 mrna levels in the hippocampus and prefrontal cortex, respectively. caa regulated the ratio of 5mc/5hmc at the promotor region of the Bdnf and Comt genes and therefore influenced gene expression, which may be a valuable therapeutic option for major depressive disorder (Mdd). in conclusion, there were epigenetic changes in the hippocampus and prefrontal cortex in cuMS rats, and caa may function as a modulator of dna methylation to regulate gene transcription, thus providing a mechanistic basis for the use of this phytochemical agent in the treatment of Mdd.

Identifying Antidepressant Effects of Brain-Derived Neurotrophic Factor and IDO1 in the Mouse Model Based on RNA-Seq Data

“…This study focused on mouse mPFC sequencing of gene modification, especially in BDNF +/− and IDO1 −/− mice. Other previous studies have reported more differential mRNA expressions in the hippocampus, and there are possibilities of molecular lateralization in other subcortical areas ( Hu et al, 2020 ; Chae et al, 2021 ). Furthermore, various abundant genes are specifically expressed in the gene-editing group and differentially expressed in the depression-like group as compared with the normal or depression-like antagonism groups, hence indicating that they serve specific functions in specific pathways ( Le et al, 2018 ; Xu et al, 2019 ).…”

Integrated analysis of phytochemical composition, pharmacokinetics, and network pharmacology to probe distinctions between the stems ofCistanche deserticolaandC. tubulosabased on antidepressant activity

“…However, there are a few studies on the antidepressant activity of the above characteristic differential and absorbed compounds, of which, only caffeic acid 24 and hydroxytyrosol 13,25 were confirmed to relieve depression-like behaviors, and echinacoside 26 and verbascoside 27 were reported to reduce the immobility times in the FST. The present study first applied network pharmacology analysis to explore the antidepressant compounds and mechanisms of CH, and the candidate bioactive compounds of CH exhibited multitarget properties and potential synergistic effects, which were consistent with our previous study.…”

Potential of Probiotics as an Adjunct for Patients with Major Depressive Disorder

“…Studies suggest 3,4‐dihydroxycinnamic acid (CaA) has antidepressant‐like effects on chronic unpredictable mild stress (CUMS) mice due to the modulation of CaA on BDNF and Comt genes that affect the expression of 5‐methylcytosine and 5‐hydroxymetylcytosine in hippocampus respectively. [ 63 ]…”