Project description:Finding the differences in gene expression in three regions of the brain, basal ganglia, white matter, and frontal cortex, in normal, HIV infected, HIV infected with neurocognitive impairment, and HIV infected with both neurocognitive impairment and encephalitis patients.
Project description:Quetiapine is an atypical neuroleptic with a pharmacological profile distinct from classic neuroleptics. It is currently approved for treating patients with schizophrenia, major depression and bipolar I disorder. However, its cellular effects remain elusive. We used microarrays to characterize RNA transcript levels in the brains of mice chronically treated with quetiapine, the neuroleptic haloperidol, or vehicle. We further characterized particular RNA transcripts in cortical cell cultures. Mice were given one of 5 treatments (vehicle, 1 mg/kg haloperidol, 0.3 mg/kg haloperidol, 100 mg/kg quetiapine, 10 mg/kg quetiapine). Pooled tissue samples were used for microarray analysis of gene expression in the frontal cortex (FC) and striatum (STR). Frontal cortex gene targets were subsequently verified with quantitative real-time PCR (qRT-PCR) from the same cohort of mice and an independent cohort.
Project description:Cellular heterogeneity may bias cell type specific epigenetic patterns leading to a dramatic increase in false positive or negative findings in psychiatric epigenetic studies. To address this issue, we performed fluorescence activated cell sorting (FACS) of neuronal nuclei in post mortem frontal cortex 58 samples followed by Illumina HM450 microarray based DNA methylation profiling. We characterized the extent of neuron and glia specific DNA methylation variation independent of disease status and identified significant cell type specific epigenetic variation at 51% of loci. DNA methylation was profiled for sorted neuronal nuclei from post mortem frontal cortex of 29 major depression and 29 matched control samples using Illumina HM450 microarrays
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Objective: To elucidate the potential effects of stressful factors for depression on the hippocampal, frontal cortex and pituitary gland genome-wide transcriptomes at the molecular level, we evaluated the transcriptomic profiles of depression rats under chronic restraint stress (CRS). Methods: Forty-eight rats were randomly divided into control, model, fluoxetine and acupuncture groups. Experimental period was 28 days. Open-field test, Sucrose preference and body weight were investigated respectively at the experiment before and after the experiment. The experiment having been finished, solexa sequencing technology (Illumina Nextseq 500/151nt) was applied to investigate and verify the altered hippocampal, frontal cortex and pituitary gland genome-wide transcriptome analysis in rats of all groups. Results: Based on the data from RNA-seq analysis, it revealed that compared the expression of genes in the control group with model group in the respective of three brain tissues, 101, 134, 148 differential expression genes were found in the hippocampus, frontal cortex and pituitary gland, respectively; compared the expression of genes in the fluoxetine group with model group in the respective of three brain tissues, 41, 46, 87 differential expression genes were found in the hippocampus, frontal cortex and pituitary gland, respectively; compared the expression of genes in the acupuncture group with model group in the respective of three brain tissues, 107, 89, 179 differential expression genes were found in the hippocampus, frontal cortex and pituitary gland, respectively. Furthermore, we used the GO (Gene ontology) analysis and KEGG (Kyo-To conservation of Genes and Genomes) pathway analysis for these differentially expressed genes. We found that the results of these two analyses were consistent, both mainly related to monoamine neurotransmitters, inflammation and immune response in control group VS model group. It is noted that this phenomenon also appears in fluoxetine group compared with model group, acupuncture group VS model group. Importantly, the antidepressant effect of acupuncture was more extensive, which was more consistent with the pathogenesis of depression induced by CRS in rats. Conclusions: Our study represents the first detailed analysis of the hippocampal, frontal cortex and pituitary gland genome-wide transcriptomes in depression rats under CRS by RNA-seq technology. The results of this study revealed multiple DEGs and possible mechanisms specifying the function of hippocampal, frontal cortex and pituitary gland in depression rats induced by CRS. These results provide a basis for further investigation of the signaling mechanisms that affect central nervous system output related to stress-sensitive depressive disorder development.
Project description:Objective: To elucidate molecular mechanisms of neurocognitive dysfunction in long-term HIV-infected individuals by assessing the microRNA (miR) profile and determining clinical and neurocognitive correlates to miR expression. Design: Analysis of miR profile in frontal cortex of retrospectively-identified autopsy cases of longitudinally-followed subjects with HIV-infection and age/sex-matched controls. HIV-subjects had semi-annual neuropsychiatric and clinical testing, at autopsy, tissue was archived. Methods: MiR repertoires were profiled from frontal cortices. Analysis of variance (ANOVA) and Tukey Honestly Sigificant Difference (HSD) tests with Benjamini-Hochberg correction for multiple comparisons were used to compare expression among the three groups. Pairwise correlations were used to identify neuropsychiatric variable that correlatee with expression of miRs. Results: MiRs were significantly different by HIV-status: miR-103, miR-125a, miR-380, miR-422a, miR-515, miR-520b, miR0618, miR-886, and miR-9. Many miRs correlated with neuropsychiatric outcomes like Learning, Memory, Executive, Verbal, and Motor deficit scores. Conclusions: MiRs are clearly dysregulated in the frontal cortex of HIV-positive individuals. Only a few miRs were significantly dysregulated in only the methamphetamine group. Our study identifies miRs that form rational targets for further inquiry on biochemical mechanisms of HIV-related neurocognitive deficits. Learning deficit score correlates with expression of more miRs than other parameters. A total of 11 HIV positive individuals were analyzed, 5 of which had a past history of methamphetamine ABUSE, and 5 age-matched HIV-negative normal Controls. Technical duplicates are included. Included are clinical and neuropsychiatric data from most recent visit before time of death. This is a retrospective autopsy study of longitudinally-followed subjects on miRNA levels in the frontal cortex.