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Regional Analysis of The Brain Transcriptome In Mice Bred For High And Low Methamphetamine Consumption

ABSTRACT: Regional Analysis of The Brain Transcriptome In Mice Bred For High And Low Methamphetamine Consumption

PROVIDER: PRJNA534467 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8949520.fastq.gz	Fastqsanger.gz
	SRR8949530.fastq.gz	Fastqsanger.gz
	SRR8949540.fastq.gz	Fastqsanger.gz
	SRR8949550.fastq.gz	Fastqsanger.gz
	SRR8949560.fastq.gz	Fastqsanger.gz

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Regional Analysis of The Brain Transcriptome In Mice Bred For High And Low Methamphetamine Consumption

Project description:Transcriptome profiling can broadly characterize drug effects and risk for addiction in the absence of drug exposure. Modern large-scale molecular methods, including RNA-sequencing (RNA-Seq), have been extensively applied to alcohol-related disease traits, but rarely to risk for methamphetamine (MA) addiction. We used RNA-Seq data from selectively bred mice with high or low risk for voluntary MA intake to construct coexpression and cosplicing networks for differential risk. Three brain reward circuitry regions, the nucleus accumbens (NAc), prefrontal cortex (PFC) and ventral midbrain (VMB), were explored. With respect to differential gene expression and wiring, the VMB was more strongly affected than either the PFC or NAc. Coexpression network connectivity was higher in the low line than the high line in the VMB, oppositely affected in the NAc, and little impacted in the PFC. Gene modules protected from the effects of selection may help to eliminate certain mechanisms from significant involvement in risk for MA intake. One such module was enriched in genes with dopamine-associated annotations. Overall, the data suggest that mitochondrial function and glutamate-mediated synaptic plasticity have key roles in the outcomes of selective breeding for high versus low levels of MA intake.

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Project description:This SuperSeries is composed of the following subset Series: GSE31695: Comparison of Differences in Gene Expression in the Ventral Tegmental Area of 5 Pairs of Rat Lines Selectively Bred for High or Low Alcohol Consumption GSE31705: Comparison of Differences in Gene Expression in the Nucleus Accumbens Shell of 5 Pairs of Rat Lines Selectively Bred for High or Low Alcohol Consumption GSE31708: Comparison of Differences in Gene Expression in the Central Nucleus of the Amygdala (CeA) of 5 Pairs of Rat Lines Selectively Bred for High or Low Alcohol Consumption Refer to individual Series

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Comparison of Differences in Gene Expression in the Nucleus Accumbens Shell of 5 Pairs of Rat Lines Selectively Bred for High or Low Alcohol Consumption

Project description:The objective of this study was to determine common innate differences in gene expression in the nucleus accumbens shell among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats. Comparison of Differences in Gene Expression in the Nucleus Accumbens Shell of 5 Pairs of Rat Lines Selectively Bred for High or Low Alcohol Consumption.

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Project description:Transcriptome profiling can broadly characterize drug effects and risk for addiction in the absence of drug exposure. Modern large-scale molecular methods, including RNA-sequencing (RNA-Seq), have been extensively applied to alcohol-related disease traits, but rarely to risk for methamphetamine (MA) addiction. We used RNA-Seq data from selectively bred mice with high or low risk for voluntary MA intake to construct coexpression and cosplicing networks for differential risk. Three brain reward circuitry regions were explored, the nucleus accumbens (NAc), prefrontal cortex (PFC), and ventral midbrain (VMB). With respect to differential gene expression and wiring, the VMB was more strongly affected than either the PFC or NAc. Coexpression network connectivity was higher in the low MA drinking line than in the high MA drinking line in the VMB, oppositely affected in the NAc, and little impacted in the PFC. Gene modules protected from the effects of selection may help to eliminate certain mechanisms from significant involvement in risk for MA intake. One such module was enriched in genes with dopamine-associated annotations. Overall, the data suggest that mitochondrial function and glutamate-mediated synaptic plasticity have key roles in the outcomes of selective breeding for high versus low levels of MA intake.

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Project description:The objective of this study was to determine common innate differences in gene expression in the ventral tegmental area (VTA) among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats. There were between 350 and 1400 unique named genes that were significantly different between the individual line-pairs. Gene Ontology (GO) and Ingenuity Pathways analyses indicated significant categories and networks in common for up to 3 line-pairs, but not for all 5 line-pairs; there were few genes in common between any of the line-pairs in these categories and networks. The overall ANOVAs of the combined data for the 5 line-pairs indicated over 1300 significant differences in expression of named genes. Ingenuity analysis revealed (a) several significant networks with clusters of genes associated with App, Egfr, Ccnd1, Itga2b, Rxra and Vcl; and (b) changes in genes within networks associated with dopamine, the glutamate synapse, Nfkb signaling, IL pathways and integrin. There were 22 genes that were significantly different in the overall ANOVA and were significantly different (in the direction) in at least 3 line-pairs, e.g., Crebl2, Gsta4, Itga9 & Itg2. In conclusion, the findings suggest that (a) different innate mechanisms may be contributing to vulnerability to high alcohol drinking behavior among the selectively bred lines, and (b) small contributions in expression of multiple genes within certain transmitter systems and intracellular signaling pathways may contribute to the disparate alcohol drinking characteristics of the 5 line-pairs. Comparison of Differences in Gene Expression in the Ventral Tegmental Area of 5 Pairs of Rat Lines Selectively Bred for High or Low Alcohol Consumption.

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