| First Author | Li Y | Year | 2022 |
| Journal | Front Mol Neurosci | Volume | 15 |
| Pages | 1068164 | PubMed ID | 36578534 |
| Mgi Jnum | J:332673 | Mgi Id | MGI:7413451 |
| Doi | 10.3389/fnmol.2022.1068164 | Citation | Li Y, et al. (2022) Inflammation-activated C/EBPbeta mediates high-fat diet-induced depression-like behaviors in mice. Front Mol Neurosci 15:1068164 |
| abstractText | 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 beta (C/EBPbeta) 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/EBPbeta expression in C/EBPbeta heterozygous knockout male mice attenuated HFD-induced depression-like behaviors, whereas Thy1-C/EBPbeta transgenic male mice (overexpressing C/EBPbeta) 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/EBPbeta heterozygous knockout mice. Remarkably, the anti-inflammatory drug aspirin strongly alleviated HFD-elicited depression-like behaviors in neuronal C/EBPbeta 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/EBPbeta transgenic mice. Therefore, our findings aim to demonstrate that the inflammation-activated neuronal C/EBPbeta promotes HFD-induced depression by diminishing BDNF expression. |
