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Objective To investigate the effect of running exercise on depression-like behaviors in chronic unpredictable stress (CUS)-induced depression mice and GABAergic interneurons, PV+ interneurons and ratio of GAD67+/PV+ cells in medial prefrontal cortex (mPFC). Methods After mouse model of depression was successfully established through CUS, these male C57BL/6 mice aged 4~6 weeks were randomly divided into control group, CUS control group and CUS+running group according to the results of sucrose preference test. The behaviors of the 3 groups were evaluated with sucrose preference test, forced swimming test and tail suspension test. The mRNA expression levels of GAD1, GAD2, PV and CCK in mPFC of mice were detected using qRT-PCR. The number of GABAergic interneurons and PV+ interneurons in mPFC of mice were quantified using immunohistochemical assay and unbiased stereological technique, and the ratio of PV+/GAD67+ cells was calculated. Results Compared with those in CUS control group, the mice from the CUS+running and control groups showed a significantly higher percentage of sucrose preference (P0.05). The mRNA level of PV, number of PV+ interneurons and ratio of PV+/GAD67+ cells in mPFC were remarkably lower in the CUS group than the CUS +running group and control group (P

N-Methyl-d-aspartate receptor (NMDAR) signaling pathway has been implicated in the pathogenesis and treatment of depression. However, the role of NMDAR subunits in depression is still unclear. In this study, alteration in all seven NMDAR subunits in several brain areas of rats exposed to chronic unpredictable mild stress (CUMS), an animal model of depression, was detected. Our findings demonstrated that: (1) CUMS could induce a reduction in sucrose preference, an indicator of typical depression-like behaviors; (2) CUMS significantly reduced the NMDAR subunits of GluN2B and GluN3 in the medial prefrontal cortex (mPFC), but not altered all seven NMDAR subunits in hippocampus and corpus callosum of rats; (3) subunit composition of NMDARs in corpus callosum was different from that in mPFC, PFC and hippocampus; and (4) the mRNA expressions of GluN2B, GluN3A and GluN3B in mPFC as well as mRNA expression of GluN2C in corpus callosum were correlated to sucrose preference in rats. These findings suggested that GluN2B and GluN3 in mPFC may contribute to the pathophysiology of depression.

Objective To investigate the effects of targeted silence/overexpression of PGC-1α in the hippocampus on depression-like behaviors in mice and on the number of glial fibrillary acidic protein positive (GFAP+) astrocytes in the subregions of the hippocampus. Methods After adaptive feeding and sucrose preference baseline adjustment, 32 male C57BL/6 mice aged 6~8 weeks were randomly divided into empty virus group (n=14), PGC-1α silencing group (n=11) and PGC-1α overexpression group (n=7). The latter 2 groups were injected with adeno-associated virus (AAV)-mediated genes silencing or overexpressing PGC-1α in the hippocampus, respectively, with aid of stereotactic injection technique. Sucrose preference test (SPT) and forced swimming test (FST) were performed to assess the depression-like behaviors, and the number of GFAP+ astrocytes in each hippocampal subregion was accurately quantified in 3 dimensions by immunohistochemistry and stereology. Results As compared with the empty virus group, the PGC-1α silencing group had significantly decreased percentage of sucrose preference (P < 0.01), prolonged immobility time in FST (P < 0.05), and larger number of GFAP+ astrocytes in both CA1 and DG subregions(P < 0.05). However, the immobility time in FST was remarkably shortened in the PGC-1α overexpression group (P < 0.01), with the number of GFAP+ astrocytes in CA1 and DG subregions diminished (P < 0.05). There was no significant difference in the percentage of sucrose preference between the empty virus group and PGC-1α overexpression group, and silencing or overexpressing PGC-1α showed no obvious impact on the number of astrocytes in CA3 subregion. Conclusion PGC-1α is closely associated with the depression-like behaviors and participates in regulating the number of GFAP+ astrocytes in CA1 and DG subregions in mice.

Epigenetic regulation is an important entry point to study the pathogenesis of selective fetal growth restriction (sFGR), and an understanding of the role of long noncoding RNAs (lncRNAs) in sFGR is lacking. Our study aimed to investigate the potential role of a lncRNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), in sFGR using molecular biology experiments and gain- or loss-of-function assays. We found that the levels of MALAT1, ERRγ, and HSD17B1 were downregulated and that of miR-424 was upregulated in the placental shares of the smaller twins. Moreover, angiogenesis was impaired in the placental share of the smaller fetus and MALAT1 could regulate the paracrine effects of trophoblasts on endothelium angiogenesis and proliferation by regulating miR-424. In trophoblasts, MALAT1 could competitively bind to miR-424 to regulate the expression of ERRγ and HSD17B1, thus regulating trophoblast invasion and migration. MALAT1 overexpression could decrease apoptosis and promote proliferation, alleviating cell damage induced by hypoxia. Taken together, the downregulation of MALAT1 can reduce the expression of ERRγ and HSD17B1 by competitively binding to miR-424, impairing the proangiogenic effect of trophoblasts, trophoblast invasion and migration, and the ability of trophoblasts to compensate for hypoxia, which may be involved in the pathogenesis of sFGR through various aspects. [ABSTRACT FROM AUTHOR]

Objective To investigate the changes of the total microglial number, density of activated microglia and inflammatory cytokines in the hippocampus of rat model of depression induced by chronic unpredictable stress (CUS). Methods Male Sprague-Dawley (SD) rats (6~8 weeks old) were randomly divided into control group (n=19) and CUS intervention group (n=48) with stratified randomization after adaptive feeding, sucrose preference baseline adjustment and screening. The rats of CUS intervention group were subjected to CUS intervention for 5 weeks. The depressive-like symptoms of 2 groups of rats were assessed with the sucrose preference test, and 16 model rats were screened out according to the results of sucrose preference. Immunohistochemical assay and stereological method were used to quantify the total number of microglia in the hippocampus of 2 groups of rats. The density of activated microglia in the hippocampus were studied with immunofluorescence assay. The contents of inflammatory cytokines in the hippocampus were measured with quantitative real-time polymerase chain reaction (qRT-PCR). Results The body mass and percentage of sucrose preference were significantly lower in the CUS model group than in the control group (P < 0.01). The numbers of the microglia in the hippocampal CA1, CA2/3 and DG regions were significantly increased in the CUS model group compared with the control group (P < 0.001, P=0.002, P=0.002), so were the density and proportion of the activated microglia in the CA1, CA2/3 and DG regions (P=0.011, P=0.015, P < 0.001; P=0.018, P=0.019, P < 0.001). Compared with the control group, the mRNA levels of inflammatory cytokines IL-1β and iNOS in the hippocampus were obviously higher in the model group (P=0.012, P=0.020). Conclusion The number of the microglia, density and proportion of activated microglia as well as levels of inflammatory cytokines are increased in the hippocampus of depression rats, indicating that the changes of hippocampal microglia might be involved in the pathogenesis of depression.