Unknown,Transcriptomics,Genomics,Proteomics

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Alterations in serum microRNA in humans with alcohol use disorders impact cell proliferation and cell death pathways and predict structural and functional changes in brain [rat miRNA 2.0]

ABSTRACT: We performed a global analysis of extracellular miRNAs in the serum of human subjects diagnosed with Alcohol Use Disorder (AUD) to identify robust biomarkers of early brain damage or dysfunction. This was performed in a set of 20 AUD subjects and 10 age-matched controls. They were subjected to comprehensive medical, neuropsychological and neuroimaging tests, followed by comparison of miRNA levels found in peripheral blood serum. The levels of miRNAs were quantified using two independent high-throughput methods: Affymetrix microarray and Illumina next-generation RNA-sequencing. Cross-species validation was performed using rat drinking models and mouse neural stem cell culture models, with tissue specificity of the serum miRNAs examined using additional RNA-sequencing of serum and body tissues in untreated rats. This data series includes the rat miRNA 2.0 GeneChip data only but is part of a larger SuperSeries (GSE71579). A total of 38 miRNA 2.0 GeneChips were run on small RNA purified from the rat blood serum samples.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Frank Middleton

PROVIDER: E-GEOD-71653 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems. We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. The current study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females Methods: Adult females from PAE, pair-fed [PF], and ad libitum-fed control [C]) groups were injected with either saline or complete FreundM-bM-^@M-^Ys adjuvant. Animals were terminated at the peak of inflammation or during resolution (days 16 and 39 post-injection, respectively); cohorts of saline-injected PAE, PF and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole genome mRNA expression microarrays. Results: Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. Conclusions: These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression, demonstrating long-term effects of PAE on the CNS response under steady-state conditions and following an inflammatory insult. Key words: prenatal alcohol exposure (PAE), ethanol, inflammation, arthritis, gene expression, rat. 192 samples, including 20 hybridization replicates

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Alterations in serum microRNA in humans with alcohol use disorders impact cell proliferation and cell death pathways and predict structural and functional changes in brain [rat miRNA 2.0]

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