Abstract
Depression is a condition with a complex etiological pattern, whose effective treatments are highly limited. MicroRNAs (miRNAs) have been investigated in intensive studies owing to their involvement in pathophysiology of mood disorders. The current study aimed to elucidate the role of miR-301b in hippocampus in mouse models of depressive-like behavior. Microarray-based prediction identified the differentially expressed gene neuronal pentraxin II (NPTX2) related to mental depression. Next, the putative miR-301b binding sites on the 3′UTR of NPTX2 were verified. Then the effect of miR-301b on cognitive function of mice with depressive-like behavior was analyzed using the Morris water maze test. In addition, the regulation of miR-301b to NPTX2 and activation of NF-κB signaling pathway was assessed. Following that, the microglia activation and inflammation in hippocampus were evaluated, with the expressions of inflammatory factors being examined. At last, microglia were flow cytometrically sorted and the inflammatory reaction was also assessed in vitro. The obtained findings revealed that miR-301b targeted and negatively regulated NPTX2. Moreover, overexpressed miR-301b activated the NF-κB signaling pathway, as reflected by increasing protein expressions of p-NF-κB. Upregulated miR-301b accelerated cognitive impairment in mice with depressive-like behavior. In addition, overexpression of miR-301b activated microglia and stimulated inflammation in hippocampus, accompanied by enhanced release of tumor necrosis factor-α (TNF-α), interleukin-Iβ (IL-Iβ) and cyclooxygenase-2(COX-2). Taken together, the evidence provided by the current study indicated that overexpression of miR-301b augmented hippocampal microglia activation, thus exacerbating cognitive impairment and inflammation in mice with depressive-like behavior by activating the NF-κB signaling pathway.
Highlights
Depression is a common psychiatric disorder, affecting approximately 300 million people across the world
The current study aims to investigate the effect of miR-301b on the activation of microglia in mouse models with depressive-like behaviors, in an attempt to shed new light on underlying mechanisms involved in cognitive impairment and inflammation
After differential expression analyses of brain tissue samples of mice with depressive-like behaviors and normal brain tissue samples, a total of 116 patients differentially expressed genes (DEGs) were obtained, among which 45 genes were significantly upregulated in the brain tissues of mice with depressive-like behaviors, and 71 genes were significantly downregulated in the brain tissues of mice with depressive-like behaviors
Summary
Depression is a common psychiatric disorder, affecting approximately 300 million people across the world. Tang et al Cell Death and Disease (2019)10:316 neuroplasticity, deteriorate cognitive function and lead to exacerbation of the condition of depression[5,6]. MiR-301a was previously reported to participate in the cell invasion of glioma through the activation of the Wnt/β-catenin pathway[12]. A recent study demonstrated that miR-301b positively regulates inflammatory responses by targeting c-Myb[13]. NF-κB activation has been demonstrated to exacerbate constant darkness-induced depression-like behavior, in addition to inhibiting hippocampal cell proliferation[17]. The current study aims to investigate the effect of miR-301b on the activation of microglia in mouse models with depressive-like behaviors, in an attempt to shed new light on underlying mechanisms involved in cognitive impairment and inflammation
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