Network preservation reveals shared and unique biological processes associated with chronic alcohol abuse in NAc and PFC.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
24
09
2020
accepted:
27
11
2020
entrez:
17
12
2020
pubmed:
18
12
2020
medline:
4
2
2021
Statut:
epublish
Résumé
Chronic alcohol abuse has been linked to the disruption of executive function and allostatic conditioning of reward response dysregulation in the mesocorticolimbic pathway (MCL). Here, we analyzed genome-wide mRNA and miRNA expression from matched cases with alcohol dependence (AD) and controls (n = 35) via gene network analysis to identify unique and shared biological processes dysregulated in the prefrontal cortex (PFC) and nucleus accumbens (NAc). We further investigated potential mRNA/miRNA interactions at the network and individual gene expression levels to identify the neurobiological mechanisms underlying AD in the brain. By using genotyped and imputed SNP data, we identified expression quantitative trait loci (eQTL) uncovering potential genetic regulatory elements for gene networks associated with AD. At a Bonferroni corrected p≤0.05, we identified significant mRNA (NAc = 6; PFC = 3) and miRNA (NAc = 3; PFC = 2) AD modules. The gene-set enrichment analyses revealed modules preserved between PFC and NAc to be enriched for immune response processes, whereas genes involved in cellular morphogenesis/localization and cilia-based cell projection were enriched in NAc modules only. At a Bonferroni corrected p≤0.05, we identified significant mRNA/miRNA network module correlations (NAc = 6; PFC = 4), which at an individual transcript level implicated miR-449a/b as potential regulators for cellular morphogenesis/localization in NAc. Finally, we identified eQTLs (NAc: mRNA = 37, miRNA = 9; PFC: mRNA = 17, miRNA = 16) which potentially mediate alcohol's effect in a brain region-specific manner. Our study highlights the neurotoxic effects of chronic alcohol abuse as well as brain region specific molecular changes that may impact the development of alcohol addiction.
Identifiants
pubmed: 33332381
doi: 10.1371/journal.pone.0243857
pii: PONE-D-20-30169
pmc: PMC7745987
doi:
Substances chimiques
MicroRNAs
0
Metallothionein
9038-94-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0243857Subventions
Organisme : NIMH NIH HHS
ID : R01 MH118239
Pays : United States
Organisme : NIAAA NIH HHS
ID : R21 AA022749
Pays : United States
Organisme : NIAAA NIH HHS
ID : F31 AA028180
Pays : United States
Organisme : NIAAA NIH HHS
ID : P50 AA022537
Pays : United States
Organisme : NIAAA NIH HHS
ID : R28 AA012725
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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