Areca catechu L.ameliorates chronic unpredictable mil stress-induced depression behavior in rats by the promotion of the BDNF signaling pathway / 中国药理学与毒理学杂志

OBJECTIVE To investigated the anti-de-pressant effects of the fruit Areca catechu L.(ACL)and elucidated its potential underlying mechanism using a rat model of chronic unpredictable mild stress(CUMS).METHODS CUMS was induced in rats to establish a depression animal model for 28 d.According to the baseline sucrose preference,the male rats were divided into six different groups.They were treated with parox-etine hydrochloride,ACL,and water once a day until the behavioral tests were performed.The levels of corticoste-rone(CORT),malondialdehyde(MDA),catalase(CAT),and total superoxide dismutase(T-SOD)in serum were de-tected using a commercial kit,and the concentrations of 5-hydroxytryptamine(5-HT)and dopamine(DA)mono-amine neurotransmitters in the brain tissues were detect-ed by liquid chromatography-tandem mass spectrometry.Doublecortin(DCX)expression in the hippocampal den-tate gyrus(DG)was determined by immunofluorescence,and the relative abundance of brain-derived neurotrophic factor(BDNF),TrkB,PI3K,p-Akt/Akt,PSD-95,and p-GSK-3β/GSK-3β of brain tissues were assayed by West-ern blotting.RESULTS ACL markedly increased sucrose preference,decreased the immobility time,and short-ened the feeding latency of CUMS-induced rats.CUMS induction resulted in marked changes in the contents of the monoamine neurotransmitters(5-HT and DA)in the hippocampus and cortex of brain tissues and the levels of CORT,MDA,CAT,and T-SOD in serum,whereas ACL administration alleviated these considerable changes.ACL promoted DCX expression in DG and increased the protein levels of BDNF,TrkB,PI3K,p-Akt/Akt,PSD-95,and p-GSK-3β/GSK-3β in the brains of CUMS-induced rats.CONCLUSION Our results indicated that ACL may improve depression-like behaviors in CUMS-induced rats by decreasing the hyperfunction and oxidative stress of the hypothalamic-pituitary-adrenal axis,stimulating hippo-campal neurogenesis,and activating the BDNF signaling pathway.

Identification of de novo Mutations in the Chinese Autism Spectrum Disorder Cohort via Whole-Exome Sequencing Unveils Brain Regions Implicated in Autism / 神经科学通报·英文版

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts are still under-represented in genome-wide genetic studies. Here, we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combined with single-cell sequencing data from the developing human brain, we found that the expression of genes with de novo mutations was specifically enriched in the pre-, post-central gyrus (PRC, PC) and banks of the superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and healthy controls, we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls, suggesting the potential structural deficits associated with ASD. Finally, we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas, the insula, as well as the frontal lobes in ASD patients. This work indicated that combinatorial analysis with genome-wide screening, single-cell sequencing, and brain imaging data reveal the brain regions contributing to the etiology of ASD.

Integrative analysis of in vivo recording with single-cell RNA-seq data reveals molecular properties of light-sensitive neurons in mouse V1

Vision formation is classically based on projections from retinal ganglion cells (RGC) to the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). Neurons in the mouse V1 are tuned to light stimuli. Although the cellular information of the retina and the LGN has been widely studied, the transcriptome profiles of single light-stimulated neuron in V1 remain unknown. In our study, in vivo calcium imaging and whole-cell electrophysiological patch-clamp recording were utilized to identify 53 individual cells from layer 2/3 of V1 as light-sensitive (LS) or non-light-sensitive (NS) by single-cell light-evoked calcium evaluation and action potential spiking. The contents of each cell after functional tests were aspirated in vivo through a patch-clamp pipette for mRNA sequencing. Moreover, the three-dimensional (3-D) morphological characterizations of the neurons were reconstructed in a live mouse after the whole-cell recordings. Our sequencing results indicated that V1 neurons with a high expression of genes related to transmission regulation, such as Rtn4r and Rgs7, and genes involved in membrane transport, such as Na/K ATPase and NMDA-type glutamatergic receptors, preferentially responded to light stimulation. Furthermore, an antagonist that blocks Rtn4r signals could inactivate the neuronal responses to light stimulation in live mice. In conclusion, our findings of the vivo-seq analysis indicate the key role of the strength of synaptic transmission possesses neurons in V1 of light sensory.

Integrative analysis of in vivo recording with single-cell RNA-seq data reveals molecular properties of light-sensitive neurons in mouse V1

Vision formation is classically based on projections from retinal ganglion cells (RGC) to the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). Neurons in the mouse V1 are tuned to light stimuli. Although the cellular information of the retina and the LGN has been widely studied, the transcriptome profiles of single light-stimulated neuron in V1 remain unknown. In our study, in vivo calcium imaging and whole-cell electrophysiological patch-clamp recording were utilized to identify 53 individual cells from layer 2/3 of V1 as light-sensitive (LS) or non-light-sensitive (NS) by single-cell light-evoked calcium evaluation and action potential spiking. The contents of each cell after functional tests were aspirated in vivo through a patch-clamp pipette for mRNA sequencing. Moreover, the three-dimensional (3-D) morphological characterizations of the neurons were reconstructed in a live mouse after the whole-cell recordings. Our sequencing results indicated that V1 neurons with a high expression of genes related to transmission regulation, such as Rtn4r and Rgs7, and genes involved in membrane transport, such as Na/K ATPase and NMDA-type glutamatergic receptors, preferentially responded to light stimulation. Furthermore, an antagonist that blocks Rtn4r signals could inactivate the neuronal responses to light stimulation in live mice. In conclusion, our findings of the vivo-seq analysis indicate the key role of the strength of synaptic transmission possesses neurons in V1 of light sensory.

Analysis of metal elements in water samples of plague foci in Yunnan Province / 中华地方病学杂志

Objective:To detect and analyze the contents of eight metal elements in water samples of plague foci in Yunnan Province.Methods:During the period from December 2015 to November 2016, the plague foci of Yulong, Jianchuan and Lianghe were selected as sampling sites, water samples were collected in areas with rodent activities in the 4 seasons of spring, summer, autumn and winter. The contents of eight metal elements calcium (Ca), iron (Fe), zinc (Zn), chromium (Cr), plumbum (Pb), manganese (Mn), cadmium (Cd) and cuprum (Cu) in water samples were measured by flame atomic absorption spectrometry (FAAS), and the data [median (interquartile distance)] were statistically analyzed.Results:Twenty-six, 58 and 54 water samples were collected from Yulong, Jianchuan and Lianghe plague foci, respectively. The contents of metal elements of Pb and Cd in water samples of the three plague foci [Yulong: 0.19 (0.78) and 0.08 (0.07) mg/L; Jianchuan: 0.23 (0.56) and 0.03 (0.06) mg/L; Lianghe: 0.13 (0.61) and 0.09 (0.08) mg/L] were higher than that of "Environmental Quality Standards for Surface Water" (Pb: 0.10 mg/L, Cd: 0.01 mg/L). There were significant differences in the contents of Ca and Cd elements among the three regions ( P < 0.05), but there was no significant difference in the contents of the other 6 metal elements among the three regions ( P > 0.05). The content of Ca element was the highest in Yulong plague foci, and the lowest in Lianghe plague foci ( P < 0.017). In the Yulong plague foci, there was no statistically significant difference in the content of Fe element in different seasons ( P > 0.05), and the differences in the contents of the other 7 metal elements were statistically significant ( P < 0.05). There was no significant difference in the content of Cr element in Jianchuan plague foci in different seasons ( P > 0.05), and the differences in the content of the other 7 metal elements were statistically significant ( P < 0.05). There was no significant difference in the content of Ca element in Lianghe plague foci in different seasons ( P > 0.05), and the differences in the content of the other 7 metal elements were statistically significant ( P < 0.05). Conclusion:The metal element contents of Pb and Cd are relatively abundant in water samples from 3 plague foci of Yunnan Province, and the seasonal variation trend of metal element content in water samples of Yulong and Jianchuan plague foci is similar.

Investigation and analysis of geographic landscape characteristics in Yulong plague natural focus, Yunnan Province / 中华地方病学杂志

Objective To investigate the geographic landscape features in Yulong plague natural focus.Methods Four altitudinal gradients (2 400-,2 600-,2 800-,≥3 000 m) were selected as study objects in Yulong plague natural focus from December 2015 to November 2016 to collect and analyze geographic landscape factors (topography and terrain,climate,water areas,vegetation and soil) based on the literatures about this plague focus.Results Yulong plague natural focus was an area with mid-mountain and subalpine topography in northwestern Yunnan Province,and its terrain had the character of lower in the southeast and higher in the northwest.This area belonged to plateau warm temperate monsoon climate of low latitude with an average month temperature 13.6 ℃ from 2005-2016,month air relative humidity averaged 59.4％,and rainfall averaged 884.5 mm a year,which concentrated mostly from June to September.About 98.1％ of the water area in Yulong County was controlled by Chin-sha River.The vegetation and soil were characterized by vertical distribution along with altitude gradients obviously.Conclusion The unique geographical landscape of the plague natural focus in Yulong County is one of important factors affecting the occurrence and epidemic of the plague.

Community structure of wild myomorpha in the plague foci of Lianghe County, Yunnan Province / 中华地方病学杂志

Objective To investigate the community structure and spatial distribution of wild myomorpha in the plague foci of Lianghe County,Yunnan Province.Methods From December 2015 to October 2016,in Mangdong,Hexi,Nangsong and other places in Lianghe County,forest landscape samples were randomly selected in different altitude gradients (1 000 ～,1 200 ～,1 400 ～,≥ 1 600 m).Peanut was used as a bait for trapping myomorpha,and the community structure of myomorpha was analyzed.Results A total of 663 myomorpha were collected and the density was 7.97％ (663/8 320),which were divided into 16 species,11 genus,5 families,and 3 orders.Rattus tanezumi (30.62％,203/663) was the dominant species.In the 1 000-＜ 1 200 m altitude gradient,the richness of myomorpha was the highest (13 kinds).In the 1 400-＜ 1 600 m altitude gradient,the index of diversity (2.094 2) was the highest.With the increase of altitude,the ecological dominance were increased,and the values were 0.672 2,0.774 2,0.842 8,and 0.882 4,respectively,whereas the evenness presented a decreasing trend,and the values were 0.269 2,0.197 1,0.142 8,and 0.162 0.Conclusions The Rattus tanezumi has presented a single dominant distribution at different elevation and the number and the species of the wild rodent with superior position have increased with the altitude increased in Lianghe focus.With the increase of altitude,the diversity and the evenness have increased,whereas the richness and the dominance have decreased.

Analysis of eight metal elements contents in rat hole soil in Yunnan plague natural foci / 中华地方病学杂志

Objective To compare and analyze the soil eight metal elements contents of rat holes of three plague foci in Yunnan Province.Methods The soils were collected from the rat holes in Yulong,Jianchuan,and Lianghe plague foci.Calcium (Ca),iron (Fe),zinc (Zn),chromium (Cr),lead (Pb),manganese (Mn),cadmium (Cd),and copper (Cu) were quantified with flame atomic absorption spectrometry (FAAS).Data input,calculation and collation were conducted through Excel 2007,and statistical software SPSS 20.0 was used to carried out statistical analysis through rank sum test.Results The medians of Ca content in the rat hole soil of Yulong County,Jianchuan County,and Lianghe County,respectively,were 85.40,308.56,and 0.00 mg/kg;the medians of Fe were 2 569.07,1 950.16,and 975.72 mg/kg;the medians of Zn were 5.64,4.02,and 2.04 mg/kg;the medians of Cr were 1.09,3.06,and 0.71 mg/kg;the medians of Pb were 3.61,29.56,and 22.80 mg/kg;the medians of Mn were 223.01,212.97,and 80.43 mg/kg;the medians of Cd were 0.00,2.02,and 2.94 mg/kg;and the medians of Cu were 1.92,1.08,and 0.51 mg/kg.The contents of eight metal elements were statistically different in the soil samples between Yulong,Jianchuan,and Lianghe plague foci (H =80.538,127.687,202.583,185.359,124.747,150.057,91.346,228.546,P ＜ 0.05).Conclusions The content of Fe in soil of the three plague foci in Yunnan Province is abundant.The contents of metal elements of Yulong County and Jianchuan County are similar.

Effect of Geraniin on Expression of Wnt3a in BMSC from Osteoporotic Rats / 昆明医科大学学报

Objective To investigate the effect of geraniin on expression of Wnt3a protein and mRNA in bone marrow stromal cell (BMSC) from osteoporotic rats. Methods The model of osteoporosis (OP) was duplicated by ovariectomy in rats. BMSCs were isolated and cultured. BMSCs from shamed rats were routinly cultured and taken as normal control, and BMSCs from OP rats were divided into model group, 1μmol/L simvastatin positive group, and geraniin group (0.01, 0.1, 1, 10, 100 μmol/L), respectively. The methods of realtime-PCR and western blot were used to assay the protein and mRNA expression of wnt3a, respectively.Results As compared with normal control group, the protein and mRNA expression of wnt3a in model group were significantly suppressed;Compared with model group, 1 μmol/L simvastatin, and 0.1, 1, 10 and 100 μmol/L geraniin significantly increased the expression of wnt3a protein and mRNA. Conclusion It is suggested that geraniin activates wnt/β-catenin pathway though increasing the expression of signaling protein wnt 3a in BMSCs from OP rats. It would be beneficial to osteogenic differentiation of BMSCs and osteogenesis.