Regional Differences and Similarities in the Brain Transcriptome for Mice Selected for Ethanol Preference From HS-CC Founders

Frontiers in Genetics

Christina Zheng¹  Robert Searles¹  Ovidiu D. Iancu¹  Priscila Darakjian¹  Shannon K. McWeeney²  Alexandre M. Colville²  Denesa R. Lockwood²  Robert Hitzemann³ 

[1] Science University, Portland, OR, United States;;Department of Behavioral Neuroscience, Oregon Health &;Department of Medical Informatics and Clinical Epidemiology, Oregon Health &

关键词: RNA-Seq;    collaborative cross;    nucleus accumbens shell;    central nucleus of amygdala (CeA);    prelimbic cortex;    network analysis;   

DOI  :  10.3389/fgene.2018.00300

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown