A multi-omic analysis of the dorsal striatum in an animal model of divergent genetic risk for alcohol use disorder.
AUD
Alcohol
Dorsal Striatum
Phosphoproteomics
Proteomics
RNA-sequencing
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
07
09
2020
received:
19
06
2020
accepted:
15
10
2020
pubmed:
29
10
2020
medline:
22
6
2021
entrez:
28
10
2020
Statut:
ppublish
Résumé
The development of selectively bred high and low alcohol-preferring mice (HAP and LAP, respectively) has allowed for an assessment of the polygenetic risk for pathological alcohol consumption and phenotypes associated with alcohol use disorder (AUD). Accumulating evidence indicates that the dorsal striatum (DS) is a central node in the neurocircuitry underlying addictive processes. Therefore, knowledge of differential gene, protein, and phosphorylated protein expression in the DS of HAP and LAP mice may foster new insights into how aberrant DS functioning may contribute to AUD-related phenotypes. To begin to elucidate these basal differences, a complementary and integrated analysis of DS tissue from alcohol-naïve male and female HAP and LAP mice was performed using RNA sequencing, quantitative proteomics, and phosphoproteomics. These datasets were subjected to a thorough analysis of gene ontology, pathway enrichment, and hub gene assessment. Analyses identified 2,108, 390, and 521 significant differentially expressed genes, proteins, and phosphopeptides, respectively between the two lines. Network analyses revealed an enrichment in the differential expression of genes, proteins, and phosphorylated proteins connected to cellular organization, cytoskeletal protein binding, and pathways involved in synaptic transmission and functioning. These findings suggest that the selective breeding to generate HAP and LAP mice may lead to a rearrangement of synaptic architecture which could alter DS neurotransmission and plasticity differentially between mouse lines. These rich datasets will serve as an excellent resource to inform future studies on how inherited differences in gene, protein, and phosphorylated protein expression contribute to AUD-related phenotypes.
Identifiants
pubmed: 33111353
doi: 10.1111/jnc.15226
pmc: PMC8076345
mid: NIHMS1641438
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1013-1031Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR002529
Pays : United States
Organisme : NIH HHS
ID : T32AA007462
Pays : United States
Organisme : NIAAA NIH HHS
ID : P60 AA007611
Pays : United States
Organisme : NIH HHS
ID : R01AA027214
Pays : United States
Organisme : NIH HHS
ID : UL1TR002529
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA027214
Pays : United States
Organisme : NIAAA NIH HHS
ID : T32 AA007462
Pays : United States
Organisme : NIAAA NIH HHS
ID : F31 AA029297
Pays : United States
Organisme : NIH HHS
ID : F32 AA026488
Pays : United States
Organisme : NIAAA NIH HHS
ID : F32 AA026488
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM077229
Pays : United States
Informations de copyright
© 2020 International Society for Neurochemistry.
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