Frontiers in Molecular Neuroscience (Dec 2022)
Inflammation-activated C/EBPβ mediates high-fat diet-induced depression-like behaviors in mice
- Yiyi Li,
- Yiyi Li,
- Hongyu Chen,
- Hongyu Chen,
- Jianhao Wang,
- Jianhao Wang,
- Jiabei Wang,
- Jiabei Wang,
- Xuan Niu,
- Xuan Niu,
- Chao Wang,
- Chao Wang,
- Dongdong Qin,
- Dongdong Qin,
- Fang Li,
- Fang Li,
- Yamei Wang,
- Yamei Wang,
- Jing Xiong,
- Jing Xiong,
- Songyan Liu,
- Songyan Liu,
- Liqin Huang,
- Liqin Huang,
- Xi Zhang,
- Xi Zhang,
- Feng Gao,
- Feng Gao,
- Dandan Gao,
- Dandan Gao,
- Mingxia Fan,
- Xuan Xiao,
- Zhi-Hao Wang,
- Zhi-Hao Wang
Affiliations
- Yiyi Li
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Yiyi Li
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Hongyu Chen
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Hongyu Chen
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Jianhao Wang
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Jianhao Wang
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Jiabei Wang
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Jiabei Wang
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Xuan Niu
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Xuan Niu
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Chao Wang
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Chao Wang
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Dongdong Qin
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Dongdong Qin
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Fang Li
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Fang Li
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Yamei Wang
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Yamei Wang
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Jing Xiong
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Jing Xiong
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Songyan Liu
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Songyan Liu
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Liqin Huang
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Liqin Huang
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Xi Zhang
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Xi Zhang
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Feng Gao
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Feng Gao
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Dandan Gao
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Dandan Gao
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- Mingxia Fan
- Animal Experiment Center, Renmin Hospital of Wuhan University, Wuhan, China
- Xuan Xiao
- Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China
- Zhi-Hao Wang
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
- Zhi-Hao Wang
- Center for Neurodegenerative Disease Research, Renmin Hospital of Wuhan University, Wuhan, China
- DOI
- https://doi.org/10.3389/fnmol.2022.1068164
- Journal volume & issue
-
Vol. 15
Abstract
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.
Keywords
