Overexpression of microRNA-301b accelerates hippocampal microglia activation and cognitive impairment in mice with depressive-like behavior through the NF-κB signaling pathway.

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-Iß (IL-Iß) 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.

Up-regulated miR-192-5p expression rescues cognitive impairment and restores neural function in mice with depression via the Fbln2-mediated TGF-ß1 signaling pathway.

Depression represents a condition characterized by cognitive deficits and neural dysfunction and has recently been correlated with microRNAs (miRs) and their respective target genes. The present study was conducted with the goal of investigating the expression of miR-192-5p and its target gene fibulin (Fbln)-2 in an attempt to evaluate their roles in the occurrence and progression of cognitive impairment and neural function in mice with chronic unpredictable mild stress (CUMS)-induced depression through regulation of the TGF-ß1 signal transduction pathway. Verification of the targeting relationship between miR-192-5p and Fbln2 was provided in the form of initial bioinformatics prediction, followed by a further verification in the form of a dual-luciferase reporter gene assay. Normal mice and models induced by CUMS were assigned into various groups, whereas mimics, inhibitors, and small interfering RNA were introduced to validate the regulatory mechanism by which miR-192-5p regulates Fbln2 depression. Novel object recognition, tail suspension testing, and Morris water maze were all employed 28 d after transfection. Hippocampal electrophysiological recordings, Golgi staining, HPLC mass spectrometry, and fluorescence immunohistochemistry were performed to further evaluate cognitive function and neuron regeneration. CUMS-induced depression was determined to represent a predisposing factor for cognitive impairment and damage to neural function in mice, highlighted by novel object recognition, learning and memory abilities, population spike amplitude, synaptic transmission, cAMP levels, neuronal regeneration, and increased behavioral changes that resemble depression. Furthermore, increased Fbln2 expression, an activated TGF-ß1 signaling pathway, and decreased expression of miR-192-5p, synaptophysin, brain-derived neurotrophic factor, N-methyl-d-aspartate receptor subunit 2B, and calmodulin-dependent protein kinase II were noted. Up-regulated miR-192-5p targeting Fbln2 acts to alleviate CUMS-induced depression by inhibiting the TGF-ß1 signaling pathway, resulting in the enhanced cognitive function in novel object recognition, learning and memory ability, population spike amplitude, synaptic transmission, neuron regeneration, and alleviation of behavioral symptoms. The central findings of the present study indicate that up-regulated levels of miR-192-5p expression act to suppress activation of the TGF-ß1 signaling pathway by means of binding to Fbln2, thereby ameliorating cognitive impairment and strengthening neural function in a mouse model of depression.-Tang, C.-Z., Yang, J.-T., Liu, Q.-H., Wang, Y.-R., Wang, W.-S. Up-regulated miR-192-5p expression rescues cognitive impairment and restores neural function in mice with depression via the Fbln2-mediated TGF-ß1 signaling pathway.

Elevated Serum Levels of Neopterin at Admission Predicts Depression After Acute Ischemic Stroke: a 6-Month Follow-Up Study.

Inflammation and cell-mediated immune activation are attributed to the pathogenesis and pathophysiology in depression. Our aim was to test the possible association between serum levels of neopterin and the development of post-stroke depression (PSD) in Chinese patients. The subjects were first-ever acute ischemic stroke patients who were hospitalized at the First Affiliated Hospital of Xinxiang Medical University during the period from December 2012 to December 2013. Clinical information and stroke severity were collected at admission. Neurological and neuropsychological evaluations were conducted at the 6-month follow-up. Serum neopterin levels were measured using fluorometry and a high performance liquid chromatography (HPLC) method. Multivariate analyses were performed using logistic regression models. During the study period, 226 patients were included and finished the 6-month follow-up. Sixty-nine patients (30.5 %) were diagnosed as having major depression at 6 months. Patients with major depression showed higher levels of serum neopterin (21.6[IQR, 18.9-25.7]nmol/L vs. 14.6[IQR, 12.2-18.4]nmol/L, P < 0.0001) at admission. In multivariate analyses, serum neopterin was an independent predictor of PSD at 6 months [odds ratio (OR): 1.952 (95 % CI, 1.358-2.805), P < 0.0001]. With an AUC of 0.850 (95 % CI, 0.797-0.902), neopterin showed a significantly greater discriminatory ability as compared with high-sensitivity C-reactive protein, age, body mass index, and National Institutes of Health and Stroke Scale score. Neopterin is a novel, independent predictor of the development of depression 6 months after stroke. This indicated that the elevated neopterin levels may play a significant role in the pathology of depression and that the pathways leading to inflammation and cell-mediated immune activation warrant further exploration.

Serum Levels of High-sensitivity C-Reactive Protein at Admission Are More Strongly Associated with Poststroke Depression in Acute Ischemic Stroke than Homocysteine Levels.

Inflammatory processes have fundamental roles in depression. The primary purpose of this study was to assess the serum levels of high-sensitivity C-reactive protein (Hs-CRP) and homocysteine (HCY) at admission to the presence of poststroke depression (PSD). From December 2012 to December 2013, first-ever acute ischemic stroke patients who were admitted to the hospital within the first 24 h after stroke onset were consecutively recruited and followed up for 6 months. Serum levels of Hs-CRP and HCY were tested at admission. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for depression at 6 months after stroke. Ninety-five patients (42.0%) showed depression (major + minor) at 6 months after admission, and in 69 patients (30.5%), this depression was classified as major. In the 69 patients with major depression, our results showed significantly higher Hs-CRP and HCY levels at admission than patients without major depression. After adjusting all other possible covariates, Hs-CRP and HCY still were independent predicators of PSD with adjusted OR of 1.332 (95% CI, 1.230-1.452; P < 0.001) and 1.138 (95% CI, 1.072-1.274; P < 0.001), respectively. The area under the receiver operating characteristic curve values of Hs-CRP and HCY were 0.765 (95% CI, 0.701-0.9825) and 0.684 (95% CI, 0.610-0.757) for PSD, respectively. The prognostic accuracy of combined model (HCY and Hs-CRP) was higher compared to those biomarkers alone and other markers. Elevated serum levels of Hs-CRP and HCY at admission were found to be associated with depression 6 months after stroke, suggesting that these alterations might participate in the pathophysiology of depression symptoms in stroke patients.

The complete mitochondrial genome of Bos gaurus gon-shan (Bovidae; Bovinae).

In the present work we undertook the complete mitochondrial genome sequencing of a wild gon-shan chinese cattle Bos gaurus gon-shan. The total length of the mitogenome was 16,356 bp with the base composition of 33.4% for A, 27.2% for T, 26.0% for C, and 13.4% for G and an A-T (60.6%)-rich feature was detected. It harbored 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes and one non-coding control region (D-loop region). The arrangement of all genes was identical to the typical mitochondrial genomes of cattle.