CD200 in dentate gyrus improves depressive-like behaviors of mice through enhancing hippocampal neurogenesis via alleviation of microglia hyperactivation.

BACKGROUND: Neuroinflammation and microglia play critical roles in the development of depression. Cluster of differentiation 200 (CD200) is an anti-inflammatory glycoprotein that is mainly expressed in neurons, and its receptor CD200R1 is primarily in microglia. Although the CD200-CD200R1 pathway is necessary for microglial activation, its role in the pathophysiology of depression remains unknown. METHODS: The chronic social defeat stress (CSDS) with behavioral tests were performed to investigate the effect of CD200 on the depressive-like behaviors. Viral vectors were used to overexpress or knockdown of CD200. The levels of CD200 and inflammatory cytokines were tested with molecular biological techniques. The status of microglia, the expression of BDNF and neurogenesis were detected with immunofluorescence imaging. RESULTS: We found that the expression of CD200 was decreased in the dentate gyrus (DG) region of mice experienced CSDS. Overexpression of CD200 alleviated the depressive-like behaviors of stressed mice and inhibition of CD200 facilitated the susceptibility to stress. When CD200R1 receptors on microglia were knocked down, CD200 was unable to exert its role in alleviating depressive-like behavior. Microglia in the DG brain region were morphologically activated after exposure to CSDS. In contrast, exogenous administration of CD200 inhibited microglia hyperactivation, alleviated neuroinflammatory response in hippocampus, and increased the expression of BDNF, which in turn ameliorated adult hippocampal neurogenesis impairment in the DG induced by CSDS. CONCLUSIONS: Taken together, these results suggest that CD200-mediated alleviation of microglia hyperactivation contributes to the antidepressant effect of neurogenesis in dentate gyrus in mice.

Effect of total glycosides of Cistanche deserticola on the energy metabolism of human HepG2 cells.

To study the anti-tumor effect of Cistanche deserticola Y. Ma, HepG2 cells were treated with 0, 3.5, 10.5, 21, 31.5, and 42 µg/ml of total glycosides (TG) from Cistanche deserticola. The HepG2 cell survival rate and 50% inhibition concentration (IC50) were detected using the CCK-8 method, and the level of reactive oxygen species (ROS) was detected by using a DCFH-DA fluorescence probe. Finally, a Seahorse XFe24 energy analyzer (Agilent, United States) was used to detect cell mitochondrial pressure and glycolytic pressure. The results showed that TG could reduce the survival rate of HepG2 cells and that the IC50 level was 35.28 µg/ml. With increasing TG concentration, the level of ROS showed a concentration-dependent upward trend. Energy metabolism showed that each dose group of TG could significantly decline the mitochondrial respiratory and glycolytic functions of HepG2 cells. In conclusion, TG could significantly inhibit the mitochondrial respiration and glycolysis functions of HepG2 cells, increase the level of ROS, and inhibit cell proliferation. Thus, this experiment pointed out that Cistanche deserticola can be used as a source of anti-cancer foods or drugs in the future. However, further studies on its mechanisms and clinical applications are needed.

Hippocampal CD39/ENTPD1 promotes mouse depression-like behavior through hydrolyzing extracellular ATP.

Emerging evidence implicates that low levels of ATP in the extracellular space may contribute to the pathophysiology of major depressive disorder (MDD). The concentration of extracellular ATP is regulated by its hydrolase ectonucleotide tri(di)phosphohydrolase (ENTPD). However, the role of ENTPD in depression remains poorly understood. Here we examine the role of CD39 (known as ENTPD1) in mouse depression-like behavior induced by chronic social defeat stress (CSDS). We demonstrate that CSDS enhances the expression and activity of CD39 in hippocampus. The CD39 functional analog apyrase also induces depression-like behavior, which can be ameliorated by ATP replenishment. Pharmacological inhibition and genetic silencing of CD39 has an antidepressant-like effect via increasing hippocampal extracellular ATP concentration, accompanied with an increase in hippocampal neurogenesis and dendritic spine numbers in defeated mice. These results suggest that hippocampal CD39 contributes to CSDS-induced depression-like behavior via hydrolyzing extracellular ATP, indicating that CD39 may be a promising new target for the treatment of depression.

Genome-wide association study of the level of blood components in Pekin ducks.

Blood components are considered to reflect nutrient metabolism and immune activity in both humans and animals. In this study, we measured 12 blood components in Pekin ducks and performed genome-wide association analysis to identify the QTLs (quantitative trait locus) using a genotyping-by-sequencing strategy. A total of 54 QTLs were identified for blood components. One genome-wide significant QTL for alkaline phosphatase was identified within the intron-region of the OTOG gene (P = 1.31E-07). Moreover, 21 genome-wide significant SNPs for the level of serum cholinesterase were identified on six different scaffolds. In addition, for serum calcium, one genome-wide significant QTL was identified in the upstream region of gene RAB11B. These results provide new markers for functional studies in Pekin ducks, and several candidate genes were identified, which may provide additional insights into specific mechanisms for blood metabolism in ducks and their potential application for duck breeding programs.

Global stability of multi-group SIR epidemic model with group mixing and human movement.

In this paper, an SIR multi-group epidemic model with group mixing and human movement is investigated. The control reproduction number ℜυ is derived and the global dynamics of the model are completely determined by the value of ℜυ. By using the graph-theoretical approach, the results show that the disease-free equilibrium is globally asymptotically stable if ℜυ<1, and the unique endemic equilibrium is globally asymptotically stable if ℜυ>1. Two numerical examples are further presented to testify the validity of the theoretical results.

A-Kinase Anchoring Protein 150 and Protein Kinase A Complex in the Basolateral Amygdala Contributes to Depressive-like Behaviors Induced by Chronic Restraint Stress.

BACKGROUND: The basolateral amygdala (BLA) has been widely implicated in the pathophysiology of major depressive disorder. A-kinase anchoring protein 150 (AKAP150) directs kinases and phosphatases to synaptic glutamate receptors, controlling synaptic transmission and plasticity. However, the role of the AKAP150 in the BLA in major depressive disorder remains poorly understood. METHODS: Depressive-like behaviors in C57BL/6J mice were developed by chronic restraint stress (CRS). Mice received either intra-BLA injection of lentivirus-expressing Akap5 short hairpin RNA or Ht-31, a peptide to disrupt the interaction of AKAP150 and protein kinase A (PKA), followed by depressive-like behavioral tests. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid glutamate receptor (AMPAR)-mediated miniature excitatory postsynaptic currents were recorded by whole-cell patch-clamp techniques. RESULTS: Chronic stress exposure induced depressive-like behaviors, which were accompanied by an increase in total and synaptic AKAP150 expression in the BLA. Accordingly, CRS facilitated the association of AKAP150 with PKA, but not of calcineurin in the BLA. Intra-BLA infusion of lentivirus-expressing Akap5 short hairpin RNA or Ht-31 prevented depressive-like behaviors and normalized phosphorylation of serine 845 and surface expression of AMPAR subunit 1 (GluA1) in the BLA of CRS mice. Finally, blockage of AKAP150-PKA complex signaling rescued the changes in AMPAR-mediated miniature excitatory postsynaptic currents in depressive-like mice. CONCLUSIONS: These results suggest that AKAP150-PKA directly modulates BLA neuronal synaptic strength, and that AKAP150-PKA-GluA1 streamline signaling complex is responsible for CRS-induced disruption of synaptic AMPAR-mediated transmission and depressive-like behaviors in mice.

SNP discovery and genotyping using Genotyping-by-Sequencing in Pekin ducks.

Genomic selection and genome-wide association studies need thousands to millions of SNPs. However, many non-model species do not have reference chips for detecting variation. Our goal was to develop and validate an inexpensive but effective method for detecting SNP variation. Genotyping by sequencing (GBS) can be a highly efficient strategy for genome-wide SNP detection, as an alternative to microarray chips. Here, we developed a GBS protocol for ducks and tested it to genotype 49 Pekin ducks. A total of 169,209 SNPs were identified from all animals, with a mean of 55,920 SNPs per individual. The average SNP density reached 1156 SNPs/MB. In this study, the first application of GBS to ducks, we demonstrate the power and simplicity of this method. GBS can be used for genetic studies in to provide an effective method for genome-wide SNP discovery.

[Effect of electroacupuncture and moxibustion pretreatment on expression of cerebral micro- RNAs and Aquaporin protein-4 in cerebral infarction rats].

OBJECTIVE: The present study aimed at observing the effect of moxibustion pretreatment on the expression of cerebral microRNAs and Aquaporin protein-4 (AQP 4) in rats with cerebral ischemia and reperfusion (CI/R), so as to reveal its mechanism underlying improvement of cerebral infarction. METHODS: A total of 130 Wistar rats were randomly divided into blank control (n = 10), CI/R model (n = 30), electroacupuncture (EA, n = 30), moxibustion (n = 30), Aspirin groups (n = 30). Before modeling, EA (2 Hz/5 Hz, 1-2 mA) or moxibustion was applied to "Baihui" (GV 20), "Fengfu" (GV 16) and "Dazhui" (GV 14) for 20 min, once daily for 7 days. The rats of the Asprin group were treated by intragastric administration of Aspirin (10 mg/kg, 1 mg/mL) , once daily for 7 days before modeling. The CI/R model was established by occlusion of the bilateral carotid arteries. The expression levels of cerebral miRNAs and AQP 4 were detected by real-time PCR and Western blot, respectively. RESULTS: Compared with the blank control group, the expression levels of cerebral miRNA 290 and miRNA 494 were significantly reduced, while that of AQP 4 was obviously up-regulated in the model group (P < 0.01). After pretreatment with EA and moxibustion, the relative expression levels of miRNA 290 and miRNA 494 were significantly higher in the EA, moxibustion and Aspirin pretreatment groups than in the model group (P < 0.01), while cortical AQP 4 expression levels were significantly lower in the EA, moxibustion and Aspirin pretreatment groups than in the model group (P < 0. 01, P < 0.05). The effects of both EA and moxibustion groups were significantly superior to those of Aspirin pretreatment group in up-regulating expression of miRNA 290 and miRNA 494 and down-regulating expression of AQP 4 (P < 0.01, P < 0.05). In addition, the EA pretreatment was markedly superior to moxibustion pretreatment in the aforementioned effects (P < 0.05). CONCLUSION EA pretreatment of GV 14, GV 16 and GV 20 can effectively up-regulate cerebral cortical miRNA 290 and miRNA 494 and down-regulate AQP 4 in CI/R rats, which may contribute to its effect in preventing the cerebral tissue from ischemia/reperfusion injury.