Proteomic insights into the antidepressant effect of oridonin

Title : Proteomic insights into the antidepressant effect of oridonin

Abstract:

Accumulative evidence has shown that immune inflammation, particularly inflammasome activity, plays an important role in the pathophysiology of MDD. We summarize the evidence on nuclear receptors (NRs), such as glucocorticoid receptor, vitamin D receptor, estrogen receptor, aryl-hydrocarbon receptor, and peroxisome proliferator-activated receptor (PPARs), in modulating the inflammasome activity and depression-associated behaviors. To develop novel medicine with this mechanism, we found that nuclear receptor Liver X receptor activator Oridonin (ORI), a bioactive diterpenoid in Isodon rubescens, exhibits antidepressant efficacy in the chronic social defeat stress (CSDS) depression model using tail suspension, sucrose consumption, and forced swimming tests. Next, proteomic analysis of prefrontal cortex was performed in ORI-treated CSDS (ORI), imipramine-treated CSDS(IMI), CSDS and control (CON) mice. ANOVA analysis (p < 0.05) identified 191 deferentially expressed proteins, with Gene Ontology (GO) analysis revealing categories related to synapse, mitochondrion and endoplasmic reticulum(ER). Protein-Protein Interaction (PPI) analysis highlighted interactions among ORI-treated deferentially expressed proteins associated with synapse, mitochondria and ER functions. Independent analysis using Parallel Reaction Monitoring (PRM) provided insights into specific proteins leading to resilience of ER/mitochondrial and synaptic functions, including ER proteins (Mrpl42, Ighm, Mrps30, et.al.); mitochondrial proteins (Cox7c, Cdv3, Naa30, Bnip, et.al); and synaptic proteins (Dcx, Rnf112, Hdac1, et.al.). Functionally, we found that the prefrontal samples of ORI-treated animals showed significant strengthening of excitatory synapse compared to inhibitory synapse. These findings offer insights into the specific and holistic molecular mechanisms underlying the pathophysiology and oridonin treatment of depression.

Biography:

Jing Du is a professor in Beijing Anding Hospital affiliated to Capital Medical University in Beijing, China. In Beijing Anding Hospital, she is mainly engaged in the research of cellular and molecular pathophysiology and neuropsychopharmacology of mental diseases such as depression, anxiety, autism and Alzheimer's disease. She was formerly a staff scientist at the National Institute of Mental Health of the National Institutes of Health(NIH) in USA. She has won many awards, such as the Award for Special Achievement issued by the National Institutes of Health of the United States. Full member of the American College of Neuropsychopharmacology (ACNP). In 2001, she began to work as a staff scientist at NIMH, NIH, leading a team to perform research on the treatment of depression, mania and stress-related mental diseases. She was invited to serve as the editorial board of "BMC neuroscience". She has published 62 SCI articles. She is recognized nationally and internationally for her research contributions and achievements in psychopharmacology.