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Changes in miRNA expression in circulating whole blood resutling from exposure to neurotoxic doses of D-amphetamine

ABSTRACT: These experiments were designed to compare the miRNA expression in whole circulating blood in animals exposed to D-amphetamine to the expression under control condition. This is the final set of RNA seq data to be generated by the experiments that have previously generated mRNA transcriptomes (GSE62368 and GSE64778). The study objectives were to detect miRNA changes in blood resulting from a neurotoxic exposure to amphetamine that may result from organ and tissue damage or immune function changes Amphetamine effects on gene expression are dependent on body temperature and indicate that many significant changes in genes related to the immune system occur, some likely in response to damage, even when animals remain normothermic during amphetamine exposure. Also, hyperthermia alone produces many changes in immune related genes in blood

OTHER RELATED OMICS DATASETS IN: PRJNA271851PRJNA264000

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE115835 | GEO | 2018/12/18

REPOSITORIES: GEO

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Project description:Oligo array analysis with bioinformatics tools identified genes with very high expression levels in the meninges, arachnoid and pial membranes, and associated vasculature (MAV) as potentially important and unique to these tissues in rat. It was also determined whether these genes were more sensitive to expression changes after a neurotoxic exposure to amphetamine (AMPH). Gene expression in the vascular rich MAV was compared to the neuronal rich tissues of the striatum and parietal cortex. In controls, 850 genes differed by more than 5-fold when comparing the MAV to both striatum and parietal cortex. Genes specifically identified with the blood-brain barrier (BBB) were also expressed at high levels indicating they may help form tight junctions in MAV. Genes with 15-fold or greater expression in MAV compared to striatum or cortex are of potential uniqueness and importance to MAV function. Many of the identified genes are abundant in different types of epithelial tissue and function in binding, transport or metabolize ions and solute, and may help MAV regulate cerebrospinal fluid. Many others with high expressions are involved in immune system function possibly serving to facilitate lymphocyte and macrophage trafficking in vasculature and cerebrospinal fluid. Expression in the MAV has similarities to the choroid plexus indicating considerable overlap in functions. Genes in MAV with a higher expression (relative to brain) were affected in greater numbers than expected by EIH and AMPH (SIGNIFICANT?). Many expression increases evoked by AMPH and EIH in MAV relate to reactive oxidative stress and inflammation. However, AMPH induced more robust alterations in the expression of genes related to ion/solute transport, lipid metabolism, bacterial infection and damage than EIH. The BBB-related genes Sox18 and Cldn5 expression decreased more with AMPH than EIH, and Cldn 9 and Esam were increase only by AMPH. It is not known how these changes affect BBB function and integrity. Gene expression patterns in MAV were compared to two regions of brain (striatum and parietal cortex) to identify genes important to MAV function and determine whether their expressions were sensitive to a neurotoxic exposure to amphetamine.

Project description:Oligo array analysis with bioinformatics tools identified genes with very high expression levels in the meninges, arachnoid and pial membranes, and associated vasculatures (MAV) which are potentially important and unique to these tissues functional capabilities in rat. It was also determined if these genes were more sensitive to expression changes after a neurotoxic exposure to environmentally induced hyperthermia (EIH) or amphetamine (AMPH). Gene expression in the MAV was compared to the neuronal rich tissues of the striatum and parietal cortex. In controls, 1,116 genes differed by more than 5-fold when comparing MAV to both striatum and parietal cortex. Genes specifically identified with the blood-brain barrier (BBB) were also expressed at high levels indicating they may help form tight junctions in MAV. The more than 300 genes having a 15-fold or greater expression in MAV compared to striatum and cortex were deemed of potential uniqueness and importance to MAV function. Many of these genes are abundant in different types of epithelial tissue and function in binding, transport or metabolism of ions and solute, and may help MAV regulate cerebrospinal fluid. Many others with high expressions are involved in immune system function possibly serving to facilitate lymphocyte and macrophage trafficking in vasculature and cerebrospinal fluid. Genes in MAV with a higher expression (relative to striatum and cortex) were affected in greater numbers than expected by EIH and AMPH. Many expression increases evoked by AMPH and EIH in MAV relate to reactive oxidative stress and inflammation. However, AMPH induced more robust alterations in the expression of genes related to ion/solute transport (Slc15a1), lipid metabolism (Fst), bacterial infection (Lbp) and oddly pancreatitis (Reg3a, Reg3b). Expression of the BBB-related genes Sox18 and Cldn5 decreased in all regions with AMPH and EIH but even more so in MAV. Esam increased with AMPH in all regions while Angpt2 was only affected in striatum and parietal cortex. It is not known how these changes affect MAV, striatum or parietal cortex tight junction function/BBB and integrity.

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Changes in miRNA expression in circulating whole blood resutling from exposure to neurotoxic doses of D-amphetamine

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