DESCRIPTION:

RNA sequencing was carried out on two striatal brain regions, caudate nucleus (CN) of the dorsal striatum and nucleus accumbens (NAc) of the ventral striatum, that are heavily implicated in Cocaine Use Disorder (CUD). Tissues were excised from postmortem samples from men with CUD and matched control subjects. Samples from NAc compared to CN in CUD diagnosed non-Hispanic white and black race individuals. Expression values were calculated by the method detailed in 'HBA-DEALS: accurate and simultaneous identification of differential expression and splicing using hierarchical Bayesian analysis' (Genome Biol. 2020, PMID: 32660516), and log base 2 of the fold change are presented with a FDR of <0.05. Down regulated genes were annotated as Ensembl gene ids. SRA Study id SRP399860; nucleus accumbens UBERON:0001882, caudate nucleus UBERON:0001873.

LABEL:

Down regulated genes from nucleus accumbens (NAc) compared to caudate nucleus (CN), in race matched CUD diagnosed individuals

SCORE TYPE:

Effect

THRESHOLD:

<= 0.5

GENES IN THRESHOLD:

0

DATE ADDED:

2023-08-08

DATE UPDATED:

2024-10-22

SPECIES:

AUTHORS:

Philipp Mews, Ashley M Cunningham, Joseph Scarpa, Aarthi Ramakrishnan, Emily M Hicks, Sarah Bolnick, Susanna Garamszegi, Li Shen, Deborah C Mash, Eric J Nestler

TITLE:

Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models.

JOURNAL:

Science advances Feb 2023, Vol 9, pp. eadd8946

ABSTRACT:

Cocaine use disorder (CUD) is an intractable syndrome, and rising overdose death rates represent a substantial public health crisis that exacts tremendous personal and financial costs on patients and society. Sharp increases in cocaine use drive the urgent need for better mechanistic insight into this chronic relapsing brain disorder that currently lacks effective treatment options. To investigate the transcriptomic changes involved, we conducted RNA sequencing on two striatal brain regions that are heavily implicated in CUD, the nucleus accumbens and caudate nucleus, from men suffering from CUD and matched controls. Weighted gene coexpression analyses identified CUD-specific gene networks enriched in ionotropic receptors and linked to lowered neuroinflammation, contrasting the proinflammatory responses found in opioid use disorder. Integration of comprehensive transcriptomic datasets from mouse cocaine self-administration models revealed evolutionarily conserved gene networks in CUD that implicate especially D1 medium spiny neurons as drivers of cocaine-induced plasticity. PUBMED: 36763659
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