Regional differences and similarities in the brain transcriptome for mice selected for ethanol preference from HS-CC founders

Alexandre M. Colville, Ovidiu Iancu, Denesa R. Lockwood, Priscila Darakjian, Shannon McWeeney, Robert Searles, Christina Zheng, Robert Hitzemann

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The high genetic complexity found in heterogeneous stock (HS-CC) mice, together with selective breeding, can be used to detect new pathways and mechanisms associated with ethanol preference and excessive ethanol consumption. We predicted that these pathways would provide new targets for therapeutic manipulation. Previously (Colville et al., 2017), we observed that preference selection strongly affected the accumbens shell (SH) genes associated with synaptic function and in particular genes associated with synaptic tethering. Here we expand our analyses to include substantially larger sample sizes and samples from two additional components of the "addiction circuit," the central nucleus of the amygdala (CeA) and the prelimbic cortex (PL). At the level of differential expression (DE), the majority of affected genes are region-specific; only in the CeA did the DE genes show a significant enrichment in GO annotation categories, e.g., neuron part. In all three brain regions the differentially variable genes were significantly enriched in a single network module characterized by genes associated with cell-to-cell signaling. The data point to glutamate plasticity as being a key feature of selection for ethanol preference. In this context the expression of Dlg2 which encodes for PSD-93 appears to have a key role. It was also observed that the expression of the clustered protocadherins was strongly associated with preference selection.

Original languageEnglish (US)
Article number300
JournalFrontiers in Genetics
Volume9
Issue numberAUG
DOIs
StatePublished - Aug 28 2018

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Keywords

  • Central nucleus of amygdala (CeA)
  • Collaborative cross
  • Network analysis
  • Nucleus accumbens shell
  • Prelimbic cortex
  • RNA-Seq

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

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