Related Experiment Video
Updated: Jul 11, 2025
Animal Models of Depression - Chronic Despair Model CDM
Published on: September 23, 2021
CircDYM attenuates microglial apoptosis via CEBPB/ZC3H4 axis in LPS-induced mouse model of depression
Zhongqiu Zhou1, Qingqing Ye2, Hui Ren1
1Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Southeast University, Nanjing, China.
Abstract:
Major depressive disorder (MDD) is a highly prevalent condition and one of the most common psychiatric disorders worldwide. Circular RNA (circRNA) has been increasingly implicated in MDD. However, a comprehensive understanding of circRNA and microglial apoptosis in depression is incomplete. Here, we show that circDYM inhibits microglial apoptosis induced by LPS via CEBPB/ZC3H4 axis. CircDYM prevents the translocation of CEBPB from cytoplasm to the nucleus by binding with CEBPB. Moreover, LPS-induced CEBPB nuclear entry downregulates the expression of ZC3H4, in which promotes autophagy and apoptosis in microglia. Taken together, our findings provide new insights into the relationship between circDYM and microglial apoptosis and shed new light on the function of this novel mechanism in depression-associated complex changes in the brain.
Insights
Circular RNA (circRNA) circDYM inhibits microglial apoptosis in depression by blocking the CEBPB/ZC3H4 pathway. This finding offers new insights into depression mechanisms and potential therapeutic targets.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Major Depressive Disorder (MDD) is a global mental health concern.
- Circular RNAs (circRNAs) are increasingly recognized for their role in MDD pathogenesis.
- The precise mechanisms linking circRNAs and microglial apoptosis in depression remain unclear.
Purpose of the Study:
- To investigate the role of circDYM in regulating microglial apoptosis.
- To elucidate the molecular pathway involving circDYM, CEBPB, and ZC3H4 in the context of depression.
- To explore potential therapeutic targets for MDD based on circRNA function.
Main Methods:
- Investigated the effect of circDYM on lipopolysaccharide (LPS)-induced microglial apoptosis.
- Utilized molecular techniques to examine the interaction between circDYM and CEBPB.
- Analyzed the downstream effects of CEBPB nuclear translocation on ZC3H4 expression and microglial autophagy/apoptosis.
Main Results:
- CircDYM was found to inhibit LPS-induced microglial apoptosis.
- CircDYM binds to CEBPB, preventing its translocation from the cytoplasm to the nucleus.
- LPS-induced CEBPB nuclear entry led to decreased ZC3H4 expression, promoting microglial autophagy and apoptosis.
Conclusions:
- CircDYM acts as a suppressor of microglial apoptosis through the CEBPB/ZC3H4 signaling axis.
- This novel mechanism provides a deeper understanding of circRNA involvement in depression.
- Findings suggest circDYM as a potential therapeutic target for managing depression-related neuroinflammation.
