Region-specific transcriptional response to chronic nicotine in rat brain

Özlen Konu, Justin K. Kane, Tanya Barrett, Marquis P. Vawter, Ruying Chang, Jennie Z. Ma, David M. Donovan, Burt Sharp, Kevin G. Becker, Ming D. Li

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Even though nicotine has been shown to modulate mRNA expression of a variety of genes, a comprehensive high-throughput study of the effects of nicotine on the tissue-specific gene expression profiles has been lacking in the literature. In this study, cDNA microarrays containing 1117 genes and ESTs were used to assess the transcriptional response to chronic nicotine treatment in rat, based on four brain regions, i.e. prefrontal cortex (PFC), nucleus accumbens (NAs), ventral tegmental area (VTA), and amygdala (AMYG). On the basis of a non-parametric resampling method, an index (called jackknifed reliability index, JRI) was proposed, and employed to determine the inherent measurement error across multiple arrays used in this study. Upon removal of the outliers, the mean correlation coefficient between duplicate measurements increased to 0.978±0.0035 from 0.941±0.045. Results from principal component analysis and pairwise correlations suggested that brain regions studied were highly similar in terms of their absolute expression levels, but exhibited divergent transcriptional responses to chronic nicotine administration. For example, PFC and NAs were significantly more similar to each other (r=0.7; P<10-14) than to either VTA or AMYG. Furthermore, we confirmed our microarray results for two representative genes, i.e. the weak inward rectifier K+ channel (TWIK-1), and phosphate and tensin homolog (PTEN) by using real-time quantitative RT-PCR technique. Finally, a number of genes, involved in MAPK, phosphatidylinositol, and EGFR signaling pathways, were identified and proposed as possible targets in response to nicotine administration.

Original languageEnglish (US)
Pages (from-to)194-203
Number of pages10
JournalBrain Research
Volume909
Issue number1-2
DOIs
StatePublished - Aug 3 2001

Fingerprint

Nicotine
Brain
Ventral Tegmental Area
Nucleus Accumbens
Amygdala
Prefrontal Cortex
Genes
Inwardly Rectifying Potassium Channel
Expressed Sequence Tags
Phosphatidylinositols
Principal Component Analysis
Oligonucleotide Array Sequence Analysis
Transcriptome
Real-Time Polymerase Chain Reaction
Phosphates
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Konu, Ö., Kane, J. K., Barrett, T., Vawter, M. P., Chang, R., Ma, J. Z., ... Li, M. D. (2001). Region-specific transcriptional response to chronic nicotine in rat brain. Brain Research, 909(1-2), 194-203. https://doi.org/10.1016/S0006-8993(01)02685-3

Region-specific transcriptional response to chronic nicotine in rat brain. / Konu, Özlen; Kane, Justin K.; Barrett, Tanya; Vawter, Marquis P.; Chang, Ruying; Ma, Jennie Z.; Donovan, David M.; Sharp, Burt; Becker, Kevin G.; Li, Ming D.

In: Brain Research, Vol. 909, No. 1-2, 03.08.2001, p. 194-203.

Research output: Contribution to journalArticle

Konu, Ö, Kane, JK, Barrett, T, Vawter, MP, Chang, R, Ma, JZ, Donovan, DM, Sharp, B, Becker, KG & Li, MD 2001, 'Region-specific transcriptional response to chronic nicotine in rat brain', Brain Research, vol. 909, no. 1-2, pp. 194-203. https://doi.org/10.1016/S0006-8993(01)02685-3
Konu Ö, Kane JK, Barrett T, Vawter MP, Chang R, Ma JZ et al. Region-specific transcriptional response to chronic nicotine in rat brain. Brain Research. 2001 Aug 3;909(1-2):194-203. https://doi.org/10.1016/S0006-8993(01)02685-3
Konu, Özlen ; Kane, Justin K. ; Barrett, Tanya ; Vawter, Marquis P. ; Chang, Ruying ; Ma, Jennie Z. ; Donovan, David M. ; Sharp, Burt ; Becker, Kevin G. ; Li, Ming D. / Region-specific transcriptional response to chronic nicotine in rat brain. In: Brain Research. 2001 ; Vol. 909, No. 1-2. pp. 194-203.
@article{bbaf7e20a870414ead0bd8d2764612e6,
title = "Region-specific transcriptional response to chronic nicotine in rat brain",
abstract = "Even though nicotine has been shown to modulate mRNA expression of a variety of genes, a comprehensive high-throughput study of the effects of nicotine on the tissue-specific gene expression profiles has been lacking in the literature. In this study, cDNA microarrays containing 1117 genes and ESTs were used to assess the transcriptional response to chronic nicotine treatment in rat, based on four brain regions, i.e. prefrontal cortex (PFC), nucleus accumbens (NAs), ventral tegmental area (VTA), and amygdala (AMYG). On the basis of a non-parametric resampling method, an index (called jackknifed reliability index, JRI) was proposed, and employed to determine the inherent measurement error across multiple arrays used in this study. Upon removal of the outliers, the mean correlation coefficient between duplicate measurements increased to 0.978±0.0035 from 0.941±0.045. Results from principal component analysis and pairwise correlations suggested that brain regions studied were highly similar in terms of their absolute expression levels, but exhibited divergent transcriptional responses to chronic nicotine administration. For example, PFC and NAs were significantly more similar to each other (r=0.7; P<10-14) than to either VTA or AMYG. Furthermore, we confirmed our microarray results for two representative genes, i.e. the weak inward rectifier K+ channel (TWIK-1), and phosphate and tensin homolog (PTEN) by using real-time quantitative RT-PCR technique. Finally, a number of genes, involved in MAPK, phosphatidylinositol, and EGFR signaling pathways, were identified and proposed as possible targets in response to nicotine administration.",
author = "{\"O}zlen Konu and Kane, {Justin K.} and Tanya Barrett and Vawter, {Marquis P.} and Ruying Chang and Ma, {Jennie Z.} and Donovan, {David M.} and Burt Sharp and Becker, {Kevin G.} and Li, {Ming D.}",
year = "2001",
month = "8",
day = "3",
doi = "10.1016/S0006-8993(01)02685-3",
language = "English (US)",
volume = "909",
pages = "194--203",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Region-specific transcriptional response to chronic nicotine in rat brain

AU - Konu, Özlen

AU - Kane, Justin K.

AU - Barrett, Tanya

AU - Vawter, Marquis P.

AU - Chang, Ruying

AU - Ma, Jennie Z.

AU - Donovan, David M.

AU - Sharp, Burt

AU - Becker, Kevin G.

AU - Li, Ming D.

PY - 2001/8/3

Y1 - 2001/8/3

N2 - Even though nicotine has been shown to modulate mRNA expression of a variety of genes, a comprehensive high-throughput study of the effects of nicotine on the tissue-specific gene expression profiles has been lacking in the literature. In this study, cDNA microarrays containing 1117 genes and ESTs were used to assess the transcriptional response to chronic nicotine treatment in rat, based on four brain regions, i.e. prefrontal cortex (PFC), nucleus accumbens (NAs), ventral tegmental area (VTA), and amygdala (AMYG). On the basis of a non-parametric resampling method, an index (called jackknifed reliability index, JRI) was proposed, and employed to determine the inherent measurement error across multiple arrays used in this study. Upon removal of the outliers, the mean correlation coefficient between duplicate measurements increased to 0.978±0.0035 from 0.941±0.045. Results from principal component analysis and pairwise correlations suggested that brain regions studied were highly similar in terms of their absolute expression levels, but exhibited divergent transcriptional responses to chronic nicotine administration. For example, PFC and NAs were significantly more similar to each other (r=0.7; P<10-14) than to either VTA or AMYG. Furthermore, we confirmed our microarray results for two representative genes, i.e. the weak inward rectifier K+ channel (TWIK-1), and phosphate and tensin homolog (PTEN) by using real-time quantitative RT-PCR technique. Finally, a number of genes, involved in MAPK, phosphatidylinositol, and EGFR signaling pathways, were identified and proposed as possible targets in response to nicotine administration.

AB - Even though nicotine has been shown to modulate mRNA expression of a variety of genes, a comprehensive high-throughput study of the effects of nicotine on the tissue-specific gene expression profiles has been lacking in the literature. In this study, cDNA microarrays containing 1117 genes and ESTs were used to assess the transcriptional response to chronic nicotine treatment in rat, based on four brain regions, i.e. prefrontal cortex (PFC), nucleus accumbens (NAs), ventral tegmental area (VTA), and amygdala (AMYG). On the basis of a non-parametric resampling method, an index (called jackknifed reliability index, JRI) was proposed, and employed to determine the inherent measurement error across multiple arrays used in this study. Upon removal of the outliers, the mean correlation coefficient between duplicate measurements increased to 0.978±0.0035 from 0.941±0.045. Results from principal component analysis and pairwise correlations suggested that brain regions studied were highly similar in terms of their absolute expression levels, but exhibited divergent transcriptional responses to chronic nicotine administration. For example, PFC and NAs were significantly more similar to each other (r=0.7; P<10-14) than to either VTA or AMYG. Furthermore, we confirmed our microarray results for two representative genes, i.e. the weak inward rectifier K+ channel (TWIK-1), and phosphate and tensin homolog (PTEN) by using real-time quantitative RT-PCR technique. Finally, a number of genes, involved in MAPK, phosphatidylinositol, and EGFR signaling pathways, were identified and proposed as possible targets in response to nicotine administration.

UR - http://www.scopus.com/inward/record.url?scp=0035800645&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035800645&partnerID=8YFLogxK

U2 - 10.1016/S0006-8993(01)02685-3

DO - 10.1016/S0006-8993(01)02685-3

M3 - Article

VL - 909

SP - 194

EP - 203

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1-2

ER -