| Title: |
Inflammation-activated C/EBPβ mediates high-fat diet-induced depression-like behaviors in mice |
| Authors: |
Yiyi Li, Hongyu Chen, Jianhao Wang, Jiabei Wang, Xuan Niu, Chao Wang, Dongdong Qin, Fang Li, Yamei Wang, Jing Xiong, Songyan Liu, Liqin Huang, Xi Zhang, Feng Gao, Dandan Gao, Mingxia Fan, Xuan Xiao, Zhi-Hao Wang |
| Source: |
Frontiers in Molecular Neuroscience, Vol 15 (2022) |
| Publisher Information: |
Frontiers Media S.A., 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Neurosciences. Biological psychiatry. Neuropsychiatry |
| Subject Terms: |
high-fat diet, depression, transcription factor, C/EBPβ, inflammation, BDNF, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571 |
| More Details: |
Depression, one of the most common causes of disability, has a high prevalence rate in patients with metabolic syndrome. Type 2 diabetes patients are at an increased risk for depression. However, the molecular mechanism coupling diabetes to depressive disorder remains largely unknown. Here we found that the neuroinflammation, associated with high-fat diet (HFD)-induced diabetes and obesity, activated the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) in hippocampal neurons. This factor repressed brain-derived neurotrophic factor (BDNF) expression and caused depression-like behaviors in male mice. Besides, the loss of C/EBPβ expression in C/EBPβ heterozygous knockout male mice attenuated HFD-induced depression-like behaviors, whereas Thy1-C/EBPβ transgenic male mice (overexpressing C/EBPβ) showed depressive behaviors after a short-term HFD. Furthermore, HFD impaired synaptic plasticity and decreased surface expression of glutamate receptors in the hippocampus of wild-type (WT) mice, but not in C/EBPβ heterozygous knockout mice. Remarkably, the anti-inflammatory drug aspirin strongly alleviated HFD-elicited depression-like behaviors in neuronal C/EBPβ transgenic mice. Finally, the genetic delivery of BDNF or the pharmacological activation of the BDNF/TrkB signaling pathway by 7,8-dihydroxyflavone reversed anhedonia in a series of behavioral tests on HFD-fed C/EBPβ transgenic mice. Therefore, our findings aim to demonstrate that the inflammation-activated neuronal C/EBPβ promotes HFD-induced depression by diminishing BDNF expression. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1662-5099 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fnmol.2022.1068164/full; https://doaj.org/toc/1662-5099 |
| DOI: |
10.3389/fnmol.2022.1068164 |
| Access URL: |
https://doaj.org/article/cb7bea7754d6439eb232b0c4c0c0e051 |
| Accession Number: |
edsdoj.b7bea7754d6439eb232b0c4c0c0e051 |
| Database: |
Directory of Open Access Journals |
