Homo sapiens
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PROVIDER: PRJNA149873 | ENA |
REPOSITORIES: ENA
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Project description:Background: TrkB-T1 is a BDNF receptor lacking a tyrosine kinase domain that is highly expressed in astrocytes and regulates BDNF-evoked calcium transients. Previous studies indicate that downregulation of TrkB-T1 in frontal cortex may be involved in neurobiological processes underlying suicide. Methods: In a microarray screening study (N=8), we interrogated all known microRNA in the frontal cortex of suicide completers with low expression of TrkB-T1 and normal controls. These findings were validated and followed up in a larger sample of cases and controls (N=55) Functional analyses included microRNA silencing, microRNA overexpression and luciferase assays to investigate specificity and to validate interactions between differentially expressed microRNA and TrkB-T1 Results: microRNAs Hsa-miR-185* and Hsa-miR-491-3p were upregulated in suicide completers with low expression of TrkB.T1 (Pnominal: 9.10-5 and 1.8.10-4 respectively; FDR-corrected p=0.031). Bioinformatic analyses revealed five putative binding sites for the DiGeorge syndrome linked microRNA Hsa-miR-185*in the 3M-bM-^@M-^YUTR of TrkB-T1, but none for Hsa-miR-491-3P. The increase of Hsa-miR-185* in frontal cortex of suicide completers was validated then confirmed in a larger, randomly selected group of suicide completers, where an inverse correlation between Hsa-miR-185* and TrkB-T1 expression was observed ( R=-0.404; p=0.002). Silencing and overexpression studies performed in human cell lines confirmed the inverse relationship between hsa-mir-185* and trkB-T1 expression. Luciferase assays demonstrated that Hsa-miR-185* binds to sequences in the 3M-bM-^@M-^YUTR of TrkB-T1. Conclusion: These results suggest that an increase of Hsa-miR-185* expression levels regulates, at least in part, the TrkB-T1 decrease observed in the frontal cortex of suicide completers and further implicate the 3MB 22q11 region in psychopathology. The microarray analysis consists in to compare the microRNA profile of four suicide completers with low TrkB-T1 expression level and four controls. Each RNA extract was labeled with Hy3 and hybridyzed with a reference sample labeled with Hy5. The reference sample was a pool of the eight RNA samples
2012-06-01 | E-GEOD-34120 | biostudies-arrayexpress
Project description:Background: TrkB-T1 is a BDNF receptor lacking a tyrosine kinase domain that is highly expressed in astrocytes and regulates BDNF-evoked calcium transients. Previous studies indicate that downregulation of TrkB-T1 in frontal cortex may be involved in neurobiological processes underlying suicide. Methods: In a microarray screening study (N=8), we interrogated all known microRNA in the frontal cortex of suicide completers with low expression of TrkB-T1 and normal controls. These findings were validated and followed up in a larger sample of cases and controls (N=55) Functional analyses included microRNA silencing, microRNA overexpression and luciferase assays to investigate specificity and to validate interactions between differentially expressed microRNA and TrkB-T1 Results: microRNAs Hsa-miR-185* and Hsa-miR-491-3p were upregulated in suicide completers with low expression of TrkB.T1 (Pnominal: 9.10-5 and 1.8.10-4 respectively; FDR-corrected p=0.031). Bioinformatic analyses revealed five putative binding sites for the DiGeorge syndrome linked microRNA Hsa-miR-185*in the 3’UTR of TrkB-T1, but none for Hsa-miR-491-3P. The increase of Hsa-miR-185* in frontal cortex of suicide completers was validated then confirmed in a larger, randomly selected group of suicide completers, where an inverse correlation between Hsa-miR-185* and TrkB-T1 expression was observed ( R=-0.404; p=0.002). Silencing and overexpression studies performed in human cell lines confirmed the inverse relationship between hsa-mir-185* and trkB-T1 expression. Luciferase assays demonstrated that Hsa-miR-185* binds to sequences in the 3’UTR of TrkB-T1. Conclusion: These results suggest that an increase of Hsa-miR-185* expression levels regulates, at least in part, the TrkB-T1 decrease observed in the frontal cortex of suicide completers and further implicate the 3MB 22q11 region in psychopathology.
2012-06-02 | GSE34120 | GEO
Project description:Four sets of six microarray experiments were conducted. Six individual RTT frontal cortices were co-hybridized with six individual control frontal cortices. For example, the frontal cortex of patient RTT1 was compared with the occipital cortex of RTT1. Additionally, where the frontal cortex of a RTT sample was compared to the frontal cortex of a control sample, the comparison between the occipital cortices was conducted between the same samples. For example RTT1 frontal cortex vs. Con4 frontal cortex, RTT1 occipital cortex vs. Con4 occipital cortex. Each experiment was repeated and the fluorescent cyanine dyes were reversed.
2010-03-07 | E-MEXP-2588 | biostudies-arrayexpress
Project description:A total of 36 postmortem brain samples (23 suicide completers, 13 control sudden death) were collected. We evaluated the proteome profile in the prefrontal cortex (Brodmann area 9, 10) with TMT-based quantification using LC-MS/MS. Several bioinformatics tools were used to elucidate biological mechanisms related to suicide. Subgroup analysis was conducted to find common differentially expressed proteins (DEPs) among various clinically different groups. Among the 9801 proteins identified in our dataset, 295 proteins were differentially expressed between suicide completers and sudden death subjects. Various bioinformatics analysis revealed that suicide completion is predominately enriched in synaptic functions and synaptogenesis especially in endocannabinoid and GABA signaling pathway. Our finding presents the largest protein pools related to suicide completion, and suggests that newly emerging neurotransmitter systems such as endocannabinoid system and synaptogenesis processes may have an impact upon the biological cascade leading to suicide.
2022-05-20 | PXD029845 | Pride
Project description:CAGEseq eQTL analysis human brain frontal cortex
| PRJNA313520 | ENA
Project description:RNAs were extracted from entorhinal cortex of human suicide patients with major depression and matched control subjects. The transcription profile was investigated by Agilent microarray platform and quantitative real-time PCR to reveal alterations in neuronal functions in this brain region.
2010-12-31 | E-MEXP-2607 | biostudies-arrayexpress
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:RNA-seq of frontal cortex in a novel mouse model of Alzheimer's disease.
2019-09-09 | E-MTAB-7856 | ExpressionAtlas
Project description:NABEC mRNA Sequencing of Human Cerebral Frontal Cortex
| PRJNA382248 | ENA
Project description:NABEC CAGE Sequencing of Human Cerebral Frontal Cortex
| PRJNA375876 | ENA