Time-dependent changes in transcriptional profiles within five rat brain regions in response to nicotine treatment.
Many years of behavioral and neurobiology studies have demonstrated broad physiological and pharmacological effects of nicotine on the central nervous system (CNS). However, the gene expression profiles associated with these effects are largely unknown. In this study, we characterized gene expression profiles in the prefrontal cortex, striatum, hypothalamus, amygdala and ventral tegmental area of the rat brain in response to subacute and chronic systemic nicotine administration using a pathway-focused microarray developed in this laboratory that contains 638 sequence-verified genes representing broad, yet targeted, biological functions. By comparing the regional effects of nicotine treatment on gene expression levels, we derived the expression profiles of targeted genes and gene families responding to the new environment created by nicotine throughout the complex connections of the CNS. While the expression of many genes was modulated by nicotine in several regions, only a few were co-modulated in multiple brain regions, suggesting region-specific transcriptional responses. Cluster analysis of significantly altered genes within each brain region over the course of nicotine treatment indicated the genes could be grouped into clusters. Subsequent ANOVA analysis demonstrated these clusters within each brain region to be significantly different at most time points. The clusters were comprised of broad functional groups, such as signaling, neurotransmission and protein modifications, demonstrating unique expression patterns within each region. Using a systematic approach to compare the different regional responses to nicotine administration will eventually provide a better understanding of how the different brain regions responding to this drug.
Li
Ming D
MD
Program in Genomics and Bioinformatics on Drug Abuse, Department of Psychiatry, The University of Texas Health Science Center, MSC 7792, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States. lim2@uthscsa.edu
Kane
Justin K
JK
Wang
Ju
J
Ma
Jennie Z
JZ
D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D016000:Cluster Analysis; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000592:standards; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
D018722:Nicotinic Agonists; D009538:Nicotine