scholarly journals Reduced Expression of Slc Genes in the VTA and NAcc of Male Mice with Positive Fighting Experience

2020 ◽  
Author(s):  
Dmitry A. Smagin ◽  
Vladimir N. Babenko ◽  
Irina L. Kovalenko ◽  
Anna G. Galyamina ◽  
Olga E. Redina ◽  
...  

ABSTRACTThere are many psychiatric medications targeting the activity of SLC transporters. Therefore, further research is needed to elucidate the expression profiles of the Slc* genes, which may serve as markers of altered brain metabolic processes and neurotransmitter activities in psychoneurological disorders. We studied differentially expressed Slc genes using the transcriptomic profiles in the ventral tegmental area (VTA), nucleus accumbens (NAcc), and prefrontal cortex (PFC) of male mice with psychosis-like behavior induced by repeated aggression experience in daily agonistic interactions which are accompanied by wins. Most of differentially expressed Slc genes in the VTA and NAcc (12 of 17 and 25 of 26, respectively) were downregulated, which was not the case in the PFC (6 and 5, up- and down, respectively). Also, the majority of these genes were shown to have brain region-specific expression profiles. In the VTA and NAcc altered expression was observed for the genes encoding the transporters of neurotransmitters as well as inorganic and organic ions, amino acids, metals, glucose, etc. This means alteration in transport functions for many substrates, which results in complete disruption of all cellular and neurotransmitter processes. The neurotransmitter systems, especially, the dopaminergic one, in male mice with positive fighting experience in daily agonistic interactions undergo changes leading to profound genomic modifications which include downregulated expression of the majority of the Slc* genes at least in the VTA and NAcc, which is attributable to chronic stimulation of the reward systems.

Author(s):  
Han-Wen Chen ◽  
Xiao-Xia Zhang ◽  
Zhu-Ding Peng ◽  
Zu-Min Xing ◽  
Yi-Wen Zhang ◽  
...  

AbstractTreatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.


2020 ◽  
Author(s):  
Xinlu Yuan ◽  
Jianjun Diao ◽  
Anqing Du ◽  
Song Wen ◽  
Ligang Zhou ◽  
...  

Abstract Background: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the hepatic cholesterol accumulation. Circular RNA (circRNA), one of noncoding RNA, involves in many liver diseases progression. However, no recent studies on circRNA expression profiles in NAFLD have been reported previously.Methods: A NAFLD mouse model was constructed by providing high-fat diet (HFD) for 32 weeks. The circRNAs expression profile in normal mice and NAFLD mice were determined using high-output RNA sequencing method and bioinformatics methods, while the differentially expressed circRNAs were confirmed using Sanger sequencing and qRT-PCR. The circRNA-miRNA network was also predicted. The biological functions of circRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).Results: The results demonstrated the successful construction of NAFLD mice model by immunohistology and serology assay. In total, 93 dysregulated circRNAs were observed, including 57 upregulated circRNAs and 36 downregulated circRNAs, in the NAFLD group. The circRNA-miRNA network revealed the complex interaction between circRNAs and its potential miRNA targets in NAFLD. The characteristic of tissue-specific expression in circRNA was demonstrated. The differentially expressed circRNAs with important biological function were also annotated using GO and KEGG. Both DDAH1 and VAV3 genes were found to be associated with the NAFLD development.Conclusions: Taken together, this study demonstrated the circRNAs expression profile and features in NAFLD, which may provide potential biological markers for the pathogenesis of NAFLD.


2020 ◽  
Author(s):  
Xiao Ma ◽  
Shuangshuang Cen ◽  
Luming Wang ◽  
Chao Zhang ◽  
Limin Wu ◽  
...  

Abstract Background: The gonad is the major factor affecting animal reproduction. The regulatory mechanism of the expression of protein-coding genes involved in reproduction still remains to be elucidated. Increasing evidence has shown that ncRNAs play key regulatory roles in gene expression in many life processes. The roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in reproduction have been investigated in some species. However, the regulatory patterns of miRNA and lncRNA in the sex biased expression of protein coding genes remains to be elucidated. In this study, we performed an integrated analysis of miRNA, messenger RNA (mRNA), and lncRNA expression profiles to explore their regulatory patterns in the female ovary and male testis of Chinese soft-shelled turtle, Pelodiscus sinensis.Results: We identified 10 446 mature miRNAs, 20 414 mRNAs and 28 500 lncRNAs in the ovaries and testes, and 633 miRNAs, 11 319 mRNAs, and 10 495 lncRNAs showed differential expression. A total of 2 814 target genes were identified for miRNAs. The predicted target genes of these differentially expressed (DE) miRNAs and lncRNAs included abundant genes related to reproductive regulation. Furthermore, we found that 189 DEmiRNAs and 5 408 DElncRNAs showed sex-specific expression. Of these, 3 DEmiRNAs and 917 DElncRNAs were testis-specific, and 186 DEmiRNAs and 4 491 DElncRNAs were ovary-specific. We further constructed complete endogenous lncRNA-miRNA-mRNA networks using bioinformatics, including 103 DEmiRNAs, 636 DEmRNAs, and 1 622 DElncRNAs. The target genes for the differentially expressed miRNAs and lncRNAs included abundant genes involved in gonadal development, including Wt1, Creb3l2, Gata4, Wnt2, Nr5a1, Hsd17, Igf2r, H2afz, Lin52, Trim71, Zar1, and Jazf1.Conclusions: In animals, miRNA and lncRNA as master regulators regulate reproductive processes by controlling the expression of mRNAs. Considering their importance, the identified miRNAs, lncRNAs, and their targets in P. sinensis might be useful for studying the molecular processes involved in sexual reproduction and genome editing to produce higher quality aquaculture animals. A thorough understanding of ncRNA-based cellular regulatory networks will aid in the improvement of P. sinensis reproductive traits for aquaculture.


Agronomy ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 819
Author(s):  
Carmen M. Pérez-Delgado ◽  
Margarita García-Calderón ◽  
María Dolores Monje-Rueda ◽  
Antonio J. Márquez ◽  
Marco Betti

Several aspects of the legume–rhizobia symbiosis are far from being completely understood, such as the transport of compounds through the symbiosome membrane and the molecular actors (receptors, transcription factors and hormones) involved in the systemic regulation of nodulation. In this work, the transcriptomes of L. japonicus plants growing under symbiotic or non-symbiotic conditions were studied in roots and shoots, in order to look for new genes involved in nodule function and regulation both at the local and systemic levels. Several of the genes differentially expressed in roots were well-known nodulins; however, other genes with unknown function were also discovered that showed univocal nodule-specific expression profiles. Transporters of the Nitrate Transporter1/Peptide Transporter Family family, putative oligopeptide transporters, as well as other uncharacterized transporters were upregulated in nodulated roots. Five transcription factors, as well as receptors/kinases and an f-box domain containing protein, all of unknown function, were also more upregulated in nodulated roots. In the shoots of nodulated plants, genes involved in jasmonic acid and indole-3-acetic acid metabolism were differentially expressed. Moreover, three genes encoding for different glutaredoxins, proteins that were recently involved in the systemic signaling of the Arabidopsis nitrogen status, were highly downregulated in the leaves of nodulated plants. Protein–protein interaction network analysis identified nitrate reductase as a central hub in nitrogen metabolism, and a putative protein of the NADH-ubiquinone complex was highly connected to several SWEET transporters. Clustering analysis of the differentially expressed genes also suggested a possible role for a previously uncharacterized ethylene-responsive transcription factor and for LBD38 homologs in L. japonicus nodule function. The new genes identified in this study represent a promising target for the understating and manipulation of symbiotic nitrogen fixation, with the aim of improving crop legumes’ productivity.


2020 ◽  
Author(s):  
Yan Sun ◽  
Jinpeng Wang ◽  
Yuhua Li ◽  
Chunhong Yang ◽  
Xiuge Wang ◽  
...  

Abstract Background: Domestic donkeys (Equus asinus) are farm animals; they are used mainly for carrying loads in the past centuries. Recently, interests on donkey milk and meat production have increased in many countries. Donkey meat is extremely popular in China due to its high nutritional value and unique flavor. Except the origin and domestication of donkeys, few genetic studies have been conducted. Moreover, data from transcriptional profiling and microRNA (miRNA) regulation of skeletal muscle tissues in donkey are scarce. Recent developments in high-throughput sequencing techniques can offer large-scale analysis of gene expression in different species. This study aimed to explore the differences of the molecular and regulation mechanisms among donkey meat, beef, and mutton using genome-wide transcriptomic analysis and proteomic methods to provide more effective genetic information.Methods: RNA sequencing and proteomic analysis (on the basis of isobaric tags for relative and absolute quantitation) on donkey, cow, and goat muscles, and miRNAs in donkey muscles were detected. We performed a comprehensive research on total RNA, including miRNAs from donkey muscles. The mRNA expression profiles were characterized and differences in single-copy homologous genes among species were analyzed.Results: Most differentially expressed genes were associated with pathways related to protein and fat synthesis and metabolism, muscle formation, and development. We identified single nucleotide polymorphisms (SNPs) in donkey muscle and alternative splicing (AS) events. A total of 57,201 putative SNPs were found, and the main SNP variations were located in known genes. Several AS events occurred in genes related to muscle fiber. Different AS events were also noted among species. Muscle proteomic data were obtained, including all expressed proteins and differentially expressed proteins. Combined transcriptomic and proteomic analysis effectively revealed pivotal mRNAs and proteins in muscles. We found five genes associated with thin and thick filaments, which indirectly explained the characteristics of donkey muscle fibers.Conclusion: RNA-seq and iTRAQ analysis revealed altered expression of genes and proteins in three kinds of muscle. In the highly expressed genes of donkey muscle, we discovered 31 expressed genes were involved in muscle contraction and skeletal muscle fiber development. Compared with mutton, five genes related to muscle fiber synthesis were found and showed differences both at transcriptional and proteome levels in donkey muscle. Meanwhile, genetic variation and regulatory factors can combine as a database to provide more valuable molecular information for further analysis.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 152-152
Author(s):  
Thomas Illmer ◽  
David Kosel ◽  
Markus A. Schaich ◽  
Christian Thiede ◽  
Andreas Neubauer ◽  
...  

Abstract Only recently, a class of gene regulatory molecules (miRNA’s) has been described that have the potential for posttranscriptional and translational gene regulation. MiRNA’s can influence critical cellular properties like proliferation and differentiation. Since these properties vary substantially in genetically defined AML subsets we have chosen to analyze AML patients with inv(16) (n=12); standard risk cytogenetic classification (mainly comprising the normal karyotype) (SR) (n=21) and with monosomy 7 or deletion7q (n=17) using DNA oligonucleotide arrays which are employing the mirVANA miRNA probe set. Principal Component Analysis (PCA) of AML samples from patients with inv(16) showed only minor differences to normal bone marrow (BM). In contrast AML patients with SR could be clearly divided in two subgroups - one subgroup that showed miRNA expression pattern close to BM and a distinctly different subgroup. Comparison of SR patient samples with BM using ANOVA tests revealed 9 differentially expressed miRNA’s (mir-223; mir-15a; mir-16; mir-203; mir-103; mir-23b; mir-107, mir-17–5p and mir23a). AML patients with aberrations of chromosome 7 showed highly distinct PCA pattern as compared to BM samples. 64 miRNA’s were found to be differentially expressed in those patients as compared to BM. All miRNA’s located on chromosome7 that were included in the array were found downregulated in AML patients with aberrant chromosome 7 (e.g.mir-335). To further substantiate the microarray data we analyzed a total of 108 AML patients with inv(16), SR cytogenetics and aberrations of chromosome 7 for mir-23a, mir-223, mir-16 and mir-335 expression by qRT-PCR. Supporting the microarray data it could be shown that the median expression levels of mir-23a, mir-223 and mir-16 were lowest in patients with SR cytogenetics, whereas AML patients with chromosome 7 aberrations showed lowest median expression for mir-335 transcripts. This was in clear contrast to the expression of mir-150, a miRNA which could be previously shown to associate with immature T-cells and which had the highest expression in AML samples with chromosome 7 aberrations. Expression of mir-150 was correlated with a high CD34 percentage in the investigated AML samples (p<0.001) whereas mir-223 did not correlate with CD34 but was strongly associated with the surface expression of CD14 (p<0.001). In an in-vitro model of G-CSF induced CD34+ stem cell differentiation mir-223 and mir-16 were slightly upregulated whereas mir-150 disappeared during the process of differentiation. Finally, the investigated miRNA were entered in a model for outcome prediction in AML samples with SR cytogenetics including known risk factors. Within this model the ratio of mutant vs. wt FLT-3 was the strongest predictor of overall survival (p<0.01). Additonally, mir-23a expression proved to be an independent negative prognostic factor for AML patients with SR cytogenetics (p<0.05). In conclusion, the presented data demonstrate specific expression profiles of miRNA’s in AML patients with different cytogenetic risk profiles. As it could be shown for patients with SR cytogenetics the observed expression profiles are likely to contribute to a deregulated differentiation and may influence therapeutic outcome.


2015 ◽  
Vol 35 (2) ◽  
pp. 663-675 ◽  
Author(s):  
Jingyun Li ◽  
Wei Long ◽  
Qian Li ◽  
Qing Zhou ◽  
Yu Wang ◽  
...  

Background: Recent studies suggest that long non-coding RNAs (lncRNAs) play crucial roles in human diseases. The function of lncRNAs in abnormal scar pathogenesis remains poorly understood. Methods: In this study, we examined the lncRNAs expression profiles among regressive and mature scars following caesarean sections. A total of 30,586 lncRNAs and 26,109 mRNAs were analyzed by microarrays (Human LncRNA Array v3.0, Arraystar, Inc.). Results: In total, we identified 1,871 lncRNAs and 817 mRNAs with differential expression between regressive and mature scar individuals (fold change≥3, p≤0.001). A set of differentially expressed lncRNA transcripts, in particular, lncRNA8975-1, AC097662.2 and RP11-586K2.1, were confirmed using qRT-PCR. Gene ontology and pathway analysis revealed that compared to mature scars, many processes over-represented in regressive scars are related to the immune system. Conclusion: Our results show significantly altered expression profiles of lncRNAs and mRNAs between regressive and mature scars. These transcripts are potential molecular targets for inhibiting abnormal scar formation following caesarean sections.


Pathogens ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 92 ◽  
Author(s):  
Sophie Rodrigues ◽  
Christine Paillard ◽  
Sabine Van Dillen ◽  
Ali Tahrioui ◽  
Jean-Marc Berjeaud ◽  
...  

Marine pathogenic bacteria are able to form biofilms on many surfaces, such as mollusc shells, and they can wait for the appropriate opportunity to induce their virulence. Vibrio tapetis can develop such biofilms on the inner surface of shells of the Ruditapes philippinarum clam, leading to the formation of a brown conchiolin deposit in the form of a ring, hence the name of the disease: Brown Ring Disease. The virulence of V. tapetis is presumed to be related to its capacity to form biofilms, but the link has never been clearly established at the physiological or genetic level. In the present study, we used RNA-seq analysis to identify biofilm- and virulence-related genes displaying altered expression in biofilms compared to the planktonic condition. A flow cell system was employed to grow biofilms to obtain both structural and transcriptomic views of the biofilms. We found that 3615 genes were differentially expressed, confirming that biofilm and planktonic lifestyles are very different. As expected, the differentially expressed genes included those involved in biofilm formation, such as motility- and polysaccharide synthesis-related genes. The data show that quorum sensing is probably mediated by the AI-2/LuxO system in V. tapetis biofilms. The expression of genes encoding the Type VI Secretion System and associated exported proteins are strongly induced, suggesting that V. tapetis activates this virulence factor when living in biofilm.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8123
Author(s):  
Zhiqiang Zhang ◽  
Wei Liu ◽  
Zongbin Ma ◽  
Wei Zhu ◽  
Lin Jia

The mevalonate (MVA) pathway is responsible for the biosynthesis of cytosolic terpenes including gossypol and its derivatives, which play an important role in the cotton plant’s defense against pathogens and herbivores. In this study, we identified and cloned 17 potentially functional genes encoding enzymes that catalyze the six steps of the MVA pathway in Gossypium arboreum. Expression pattern analysis by qRT-PCR demonstrated that these genes had tissue-specific expression profiles and were most prevalently expressed in roots. Moreover, these genes were up-regulated in response to several elicitors, including methyl jasmonate and salicylic acid, as well as Verticillium dahliae infection and Helicoverpa armigera infestation. This indicates that the MVA pathway genes are involved in the signaling pathway regulated by exogenous hormones and the resistance of cotton plants to pathogens and herbivores. Our results improve the understanding of cytosolic terpene biosynthesis in Gossypium species and lay the foundation for further research on gossypol biosynthesis.


2020 ◽  
Author(s):  
Xinlu Yuan ◽  
Jianjun Diao ◽  
Anqing Du ◽  
Song Wen ◽  
Ligang Zhou ◽  
...  

Abstract Background: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the hepatic cholesterol accumulation. Circular RNA (circRNA), one of noncoding RNA, involves in many liver diseases progression. However, no recent studies on circRNA expression profiles in NAFLD have been reported previously. Methods: A NAFLD mouse model was constructed by providing high-fat diet (HFD) for 32 weeks. The circRNAs expression profile in normal mice and NAFLD mice were determined using high-output RNA sequencing method and bioinformatics methods, while the differentially expressed circRNAs were confirmed using Sanger sequencing and qRT-PCR. The circRNA-miRNA network was also predicted. The biological functions of circRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: The results demonstrated the successful construction of NAFLD mice model by immunohistology and serology assay. In total, 93 dysregulated circRNAs were observed, including 57 upregulated circRNAs and 36 downregulated circRNAs, in the NAFLD group. The circRNA-miRNA network revealed the complex interaction between circRNAs and its potential miRNA targets in NAFLD. The characteristic of tissue-specific expression in circRNA was demonstrated. The differentially expressed circRNAs with important biological function were also annotated using GO and KEGG. Both DDAH1 and VAV3 genes were found to be associated with the NAFLD development. Conclusions: Taken together, this study demonstrated the circRNAs expression profile and features in NAFLD, which may provide potential biological markers for the pathogenesis of NAFLD.


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