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

3 Citations (Scopus)

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

Fingerprint

Transcriptome
Ethanol
Brain
Genes
Gene Regulatory Networks
Sample Size
Glutamic Acid
Gene Expression
Neurons
Central Amygdaloid Nucleus
Therapeutics

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)

Cite this

Regional differences and similarities in the brain transcriptome for mice selected for ethanol preference from HS-CC founders. / Colville, Alexandre M.; Iancu, Ovidiu; Lockwood, Denesa R.; Darakjian, Priscila; McWeeney, Shannon; Searles, Robert; Zheng, Christina; Hitzemann, Robert.

In: Frontiers in Genetics, Vol. 9, No. AUG, 300, 28.08.2018.

Research output: Contribution to journalArticle

@article{1061c61bc49a47faafaa260042b7d9fd,
title = "Regional differences and similarities in the brain transcriptome for mice selected for ethanol preference from HS-CC founders",
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.",
keywords = "Central nucleus of amygdala (CeA), Collaborative cross, Network analysis, Nucleus accumbens shell, Prelimbic cortex, RNA-Seq",
author = "Colville, {Alexandre M.} and Ovidiu Iancu and Lockwood, {Denesa R.} and Priscila Darakjian and Shannon McWeeney and Robert Searles and Christina Zheng and Robert Hitzemann",
year = "2018",
month = "8",
day = "28",
doi = "10.3389/fgene.2018.00300",
language = "English (US)",
volume = "9",
journal = "Frontiers in Genetics",
issn = "1664-8021",
publisher = "Frontiers Media S. A.",
number = "AUG",

}

TY - JOUR

T1 - Regional differences and similarities in the brain transcriptome for mice selected for ethanol preference from HS-CC founders

AU - Colville, Alexandre M.

AU - Iancu, Ovidiu

AU - Lockwood, Denesa R.

AU - Darakjian, Priscila

AU - McWeeney, Shannon

AU - Searles, Robert

AU - Zheng, Christina

AU - Hitzemann, Robert

PY - 2018/8/28

Y1 - 2018/8/28

N2 - 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.

AB - 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.

KW - Central nucleus of amygdala (CeA)

KW - Collaborative cross

KW - Network analysis

KW - Nucleus accumbens shell

KW - Prelimbic cortex

KW - RNA-Seq

UR - http://www.scopus.com/inward/record.url?scp=85052905094&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052905094&partnerID=8YFLogxK

U2 - 10.3389/fgene.2018.00300

DO - 10.3389/fgene.2018.00300

M3 - Article

AN - SCOPUS:85052905094

VL - 9

JO - Frontiers in Genetics

JF - Frontiers in Genetics

SN - 1664-8021

IS - AUG

M1 - 300

ER -