Dataset Information

Expression data of SHSY5Y cells after cocaine exposure

ABSTRACT: The aim of the study was to evaluate cocaine-induced changes in gene expression in a dopaminergic model. Cocaine reward and reinforcing effects are mediated mainly by dopaminergic neurotransmission. In this study we aimed at evaluating gene expression changes induced by acute cocaine exposure on SH-SY5Y differentiated cells, which have been widely used as a dopaminergic neuronal model. Expression changes and a concomitant increase in neuronal activity were observed 6 hours after a 5 uM cocaine exposure, whereas no changes in gene expression nor in neuronal activity took place at 1 uM cocaine. A total of 756 differentially expressed genes, mainly related to regulation of transcription and gene expression, cell cycle, adhesion and cell projection, as well as MAPK, CREB, neurotrophin and neuregulin signaling pathways. Genes displaying altered expression were subsequently targeted with predicted functional SNPs in a case-control association study in a sample of 806 cocaine-dependent patients and 817 controls. This study highlighted associations between cocaine dependence and five SNPs predicted to alter microRNA binding at the 3’UTR of the NFAT5 gene. The association of SNP rs1437134 with cocaine dependence survived the Bonferroni correction for multiple testing. A functional effect was confirmed for this variant by a luciferase reporter assay, with lower expression observed for the rs1437134G allele, which was more pronounced in the presence of hsa-miR-509. However, brain volumes in regions of relevance to addiction, as assessed with MRI, did not correlate with NFAT5 variation. These results suggest that the NFAT5 gene, which is up-regulated a few hours after cocaine exposure, may be involved in the genetic predisposition to cocaine dependence.

ORGANISM(S): Homo sapiens

PROVIDER: GSE71939 | GEO | 2016/01/01

SECONDARY ACCESSION(S): PRJNA292553

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:<p>This project characterizes DNA methylation and gene expression changes that occur in the human brain, specifically in neurons from the rostral striatum. Major advances from NIDA funded initiatives for noninvasive neuroimaging studies have made it possible to study neuroanatomical, neurochemical and functional changes in the human brain that contribute to the vulnerability to abuse drugs, together with the neurotoxic consequences of years of drug misuse. Animal models have been developed to explain the fundamental behavioral and biological mechanisms of addiction, including reward, tolerance and dependence. From these studies, we learned that cocaine abuse not only alters the epigenetic status of genes, but also induces particular epigenetic modifications depending on the frequency of the drug's administration. Certain genes are switched on by infrequent (short-term exposure) administration, while others are switched on only after chronic administration (addiction/dependence). Animal studies have also suggested that cocaine-seeking habits modeling chronic cocaine addiction in humans depend upon dopamine-dependent serial connectivity linking the ventral (nucleus accumbens) with the dorsal striatum (caudate nucleus). The primary goal of this study is to identify DNA methylation and gene expression changes that occur in the transition from recreational cocaine use to cocaine addiction. High throughput sequencing studies were designed to investigate unique postmortem human brain specimens from individuals that met criteria for cocaine dependence, as compared to unaffected age-matched controls.</p> <p>Brain biospecimens were available from the University of Miami Brain Endowment BankTM, from a collection of phenotypically well-characterized postmortem tissues sampled from chronic cocaine abusers that came to autopsy. This biobank of postmortem brain specimens and annotated genomic data serve as a research resource to support NIDA's scientific mission.</p>

Dataset Information

Expression data of SHSY5Y cells after cocaine exposure

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets