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Evidence from Mouse and Man for a Role of Neuregulin 3 in Nicotine Dependence

Addiction to nicotine and ability to quit smoking are influenced by genetic factors. We used functional genomic approaches (chromatin immunoprecipitation (ChIP) and whole genome sequencing) to identify CREB targets following chronic nicotine administration and withdrawal in rodents. fWe found that c...

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Autores principales: Turner, Jill R., Ray, Riju, Lee, Bridgin, Everett, Logan, Xiang, Jing, Jepson, Christopher, Kaestner, Klaus H., Lerman, Caryn, Blendy, Julie A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877725/
https://www.ncbi.nlm.nih.gov/pubmed/23999525
http://dx.doi.org/10.1038/mp.2013.104
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author Turner, Jill R.
Ray, Riju
Lee, Bridgin
Everett, Logan
Xiang, Jing
Jepson, Christopher
Kaestner, Klaus H.
Lerman, Caryn
Blendy, Julie A.
author_facet Turner, Jill R.
Ray, Riju
Lee, Bridgin
Everett, Logan
Xiang, Jing
Jepson, Christopher
Kaestner, Klaus H.
Lerman, Caryn
Blendy, Julie A.
author_sort Turner, Jill R.
collection PubMed
description Addiction to nicotine and ability to quit smoking are influenced by genetic factors. We used functional genomic approaches (chromatin immunoprecipitation (ChIP) and whole genome sequencing) to identify CREB targets following chronic nicotine administration and withdrawal in rodents. fWe found that chronic nicotine and withdrawal differentially modulate CREB binding to the gene for Neuregulin 3 (NRG3). Quantitative analysis of saline, nicotine, and nicotine withdrawal in two biological replicates corroborate this finding, with NRG3 increases in both mRNA and protein following withdrawal from chronic nicotine treatment. To translate these data for human relevance, single nucleotide polymorphisms (SNPs) across NRG3 were examined for association with prospective smoking cessation among smokers of European ancestry treated with transdermal nicotine in two independent cohorts. Individual SNP and haplotype analysis support association of NRG3 SNPs and smoking cessation success. NRG3 is a neural-enriched member of the EGF family, and a specific ligand for the receptor tyrosine kinase ErbB4, which is also up-regulated following nicotine treatment and withdrawal. Mice with significantly reduced levels of NRG3 or pharmacological inhibition of ErbB4 show similar reductions in anxiety following nicotine withdrawal compared to control animals, suggesting a role for NRG3 in nicotine dependence. While the function of the SNP in NRG3 in humans is not known, these data suggest that Nrg3/ErbB4 signaling may be an important factor in nicotine dependence.
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spelling pubmed-38777252015-01-01 Evidence from Mouse and Man for a Role of Neuregulin 3 in Nicotine Dependence Turner, Jill R. Ray, Riju Lee, Bridgin Everett, Logan Xiang, Jing Jepson, Christopher Kaestner, Klaus H. Lerman, Caryn Blendy, Julie A. Mol Psychiatry Article Addiction to nicotine and ability to quit smoking are influenced by genetic factors. We used functional genomic approaches (chromatin immunoprecipitation (ChIP) and whole genome sequencing) to identify CREB targets following chronic nicotine administration and withdrawal in rodents. fWe found that chronic nicotine and withdrawal differentially modulate CREB binding to the gene for Neuregulin 3 (NRG3). Quantitative analysis of saline, nicotine, and nicotine withdrawal in two biological replicates corroborate this finding, with NRG3 increases in both mRNA and protein following withdrawal from chronic nicotine treatment. To translate these data for human relevance, single nucleotide polymorphisms (SNPs) across NRG3 were examined for association with prospective smoking cessation among smokers of European ancestry treated with transdermal nicotine in two independent cohorts. Individual SNP and haplotype analysis support association of NRG3 SNPs and smoking cessation success. NRG3 is a neural-enriched member of the EGF family, and a specific ligand for the receptor tyrosine kinase ErbB4, which is also up-regulated following nicotine treatment and withdrawal. Mice with significantly reduced levels of NRG3 or pharmacological inhibition of ErbB4 show similar reductions in anxiety following nicotine withdrawal compared to control animals, suggesting a role for NRG3 in nicotine dependence. While the function of the SNP in NRG3 in humans is not known, these data suggest that Nrg3/ErbB4 signaling may be an important factor in nicotine dependence. 2013-09-03 2014-07 /pmc/articles/PMC3877725/ /pubmed/23999525 http://dx.doi.org/10.1038/mp.2013.104 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Turner, Jill R.
Ray, Riju
Lee, Bridgin
Everett, Logan
Xiang, Jing
Jepson, Christopher
Kaestner, Klaus H.
Lerman, Caryn
Blendy, Julie A.
Evidence from Mouse and Man for a Role of Neuregulin 3 in Nicotine Dependence
title Evidence from Mouse and Man for a Role of Neuregulin 3 in Nicotine Dependence
title_full Evidence from Mouse and Man for a Role of Neuregulin 3 in Nicotine Dependence
title_fullStr Evidence from Mouse and Man for a Role of Neuregulin 3 in Nicotine Dependence
title_full_unstemmed Evidence from Mouse and Man for a Role of Neuregulin 3 in Nicotine Dependence
title_short Evidence from Mouse and Man for a Role of Neuregulin 3 in Nicotine Dependence
title_sort evidence from mouse and man for a role of neuregulin 3 in nicotine dependence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877725/
https://www.ncbi.nlm.nih.gov/pubmed/23999525
http://dx.doi.org/10.1038/mp.2013.104
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