Auraptene-ameliorating depressive-like behaviors induced by lipopolysaccharide combined with chronic unpredictable mild stress in mice mitigate hippocampal neuroinflammation mediated by microglia.

An inflammatory response is one of the pathogeneses of depression. The anti-inflammatory and neuroprotective effects of auraptene have previously been confirmed. We established an inflammatory depression model by lipopolysaccharide (LPS) injection combined with unpredictable chronic mild stress (uCMS), aiming to explore the effects of auraptene on depressive-like behaviors in adult mice. Mice were divided into a control group, vehicle group, fluoxetine group, celecoxib group, and auraptene group. Then, behavioral tests were conducted to evaluate the effectiveness of auraptene in ameliorating depressive-like behavior. Cyclooxygenase-2 (COX-2), C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were examined by ELISA. Interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-ß (TGF-ß) were examined by protein chip technology. The morphology of microglia was observed by the immunohistochemical method. The data showed that, compared with the control group, the vehicle group mice exhibited a depressive-like behavioral phenotype, accompanied by an imbalance in inflammatory cytokines and the activation of microglia in the hippocampus. The depressive behaviors of the auraptene group's mice were significantly alleviated, along with the decrease in pro-inflammatory factors and increase in anti-inflammatory factors, while the activation of microglia was inhibited in the hippocampus. Subsequently, we investigated the role of auraptene in vitro-cultured BV-2 cells treated with LPS. The analysis showed that auraptene downregulated the expression of IL-6, TNF-α, and NO, and diminished the ratio of CD86/CD206. The results showed that auraptene reduced the excessive phagocytosis and ROS production of LPS-induced BV2 cells. In conclusion, auraptene relieved depressive-like behaviors in mice probably via modulating hippocampal neuroinflammation mediated by microglia.

N-palmitoylethanolamine modulates hippocampal neuroplasticity in rats with stress-induced depressive behavior phenotype.

Bioactive lipid mediator N-palmitoylethanolamide (PEA) is an endocannabinoid-like molecule. Based on our previous data, this study aimed to further investigate the antidepressant property of PEA via the peroxisome proliferator-activated receptor alpha (PPARα) pathway, focusing on the intervention of PEA on hippocampal neuroplasticity. Behavioral tests were performed in rats induced by unpredictable chronic mild stress (uCMS) in the last week of the experiment, and then the brain tissue samples were retained for subsequent immunohistochemical detection and Western blot analysis. In vitro, the apoptosis of HT22 cells induced by CORT and apoptosis-related proteins were detected by Hoechst staining and Western blot, respectively. The results showed that PEA ameliorated the depression-like phenotype in rats induced by uCMS, prevented the uCMS-induced reduction in the number of BrdU-positive cells, and increased BrdU/NeuN co-localization in the hippocampus, and upregulated the levels of synapse associated protein NCAM, MAP2, SYN and PSD95 in the hippocampus. Hoechst staining results showed that PEA significantly increased the CORT-induced reduction in the number of hippocampal neurons. Western blot analysis showed that PEA decreased the expression of caspase-3 and c-caspase-3, and increased the ratio of Bcl-2/Bax in CORT-induced HT22 cells. MK886, a PPARα antagonist, partially or completely reversed these effects. In conclusion, the therapeutic potential of PEA for depressive mood disorders may be through targeting the hippocampal neuroplasticity, including increasing adult neurogenesis and synaptic plasticity, as well as down-regulated neuronal apoptosis, to remodel hippocampal circuitries upon functional integration and PPARα pathway may be involved in this process.

Comparative and population genomics of buckwheat species reveal key determinants of flavor and fertility.

Common buckwheat (Fagopyrum esculentum) is an ancient crop with a world-wide distribution. Due to its excellent nutritional quality and high economic and ecological value, common buckwheat is becoming increasingly important throughout the world. The availability of a high-quality reference genome sequence and population genomic data will accelerate the breeding of common buckwheat, but the high heterozygosity due to the outcrossing nature has greatly hindered the genome assembly. Here we report the assembly of a chromosome-scale high-quality reference genome of F. esculentum var. homotropicum, a homozygous self-pollinating variant of common buckwheat. Comparative genomics revealed that two cultivated buckwheat species, common buckwheat (F. esculentum) and Tartary buckwheat (F. tataricum), underwent metabolomic divergence and ecotype differentiation. The expansion of several gene families in common buckwheat, including FhFAR genes, is associated with its wider distribution than Tartary buckwheat. Copy number variation of genes involved in the metabolism of flavonoids is associated with the difference of rutin content between common and Tartary buckwheat. Furthermore, we present a comprehensive atlas of genomic variation based on whole-genome resequencing of 572 accessions of common buckwheat. Population and evolutionary genomics reveal genetic variation associated with environmental adaptability and floral development between Chinese and non-Chinese cultivated groups. Genome-wide association analyses of multi-year agronomic traits with the content of flavonoids revealed that Fh05G014970 is a potential major regulator of flowering period, a key agronomic trait controlling the yield of outcrossing crops, and that Fh06G015130 is a crucial gene underlying flavor-associated flavonoids. Intriguingly, we found that the gene translocation and sequence variation of FhS-ELF3 contribute to the homomorphic self-compatibility of common buckwheat. Collectively, our results elucidate the genetic basis of speciation, ecological adaptation, fertility, and unique flavor of common buckwheat, and provide new resources for future genomics-assisted breeding of this economically important crop.