Functional gene expression differences between inbred alcohol-preferring and –non-preferring rats in five brain regions

Kimpel, Mark W.; Strother, Wendy N.; McClintick, Jeanette N.; Carr, Lucinda G.; Liang, Tiebing; Edenberg, Howard J.; McBride, William J.

doi:10.1016/j.alcohol.2007.03.003

Cited by 107 publications

(108 citation statements)

References 92 publications

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“…Of the remaining 3 genes, Map1b changed in the same direction with both measures (however, the RT-PCR values were not statistically different), Camk4 was not changed in the RT-PCR measure, and Nrxn3 changed significantly in both measures, but in opposite directions (Table 7). Similar to previous studies from our lab (Edenberg et al, 2005;Kimpel et al, 2007), there was a high degree of concordance between the microarray and RT-PCR results. However, the lack of agreement between the two measures for Camk4 and Nrxn3 suggests the results for these two genes are inconclusive.…”

Section: Quantitative Rt-pcr Confirmationsupporting

confidence: 76%

Differential gene expression in the nucleus accumbens with ethanol self-administration in inbred alcohol-preferring rats

Rodd

Kimpel

Edenberg

et al. 2008

Pharmacology Biochemistry and Behavior

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The current study examined the effects of operant ethanol (EtOH) self-administration on gene expression in the nucleus accumbens (ACB) and amygdala (AMYG) of inbred alcohol-preferring (iP) rats. Rats self-trained on a standard two-lever operant paradigm to administer either waterwater, EtOH (15% v/v)-water, or saccharin (SAC; 0.0125% g/v)-water. Animals were killed 24 hr after the last operant session, and the ACB and AMYG dissected; RNA was extracted and purified for microarray analysis. For the ACB, there were 513 significant differences at the p < 0.01 level in named genes: 55 between SAC and water; 215 between EtOH and water, and 243 between EtOH and SAC. In the case of the AMYG (p < 0.01), there were 48 between SAC and water, 23 between EtOH and water, and 63 between EtOH and SAC group. Gene Ontology (GO) analysis indicated that differences in the ACB between the EtOH and SAC groups could be grouped into 15 significant (p < 0.05) categories, which included major categories such as synaptic transmission, cell and ion homeostasis, and neurogenesis, whereas differences between the EtOH and water groups had only 4 categories, which also included homeostasis and synaptic transmission. Several genes were in common between the EtOH and both the SAC and water groups in the synaptic transmission (e.g., Cav2, Nrxn, Gabrb2, Gad1, Homer1) and homeostasis Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript (S100b, Prkca, Ftl1) categories. Overall, the results suggest that changes in gene expression in the ACB of iP rats are associated with the reinforcing effects of EtOH.

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Section: Quantitative Rt-pcr Confirmationsupporting

confidence: 76%

Differential gene expression in the nucleus accumbens with ethanol self-administration in inbred alcohol-preferring rats

Rodd

Kimpel

Edenberg

et al. 2008

Pharmacology Biochemistry and Behavior

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“…The neuroimmune transcriptome & alcohol dependence: potential for targeted therapies Review identified immune and inflammatory transcripts and pathways in alcohol-exposed tissue from mice, rats and human tissue [3][4][5]34,[102][103][104]. Several immune genes found in these microarray studies were validated in rodent ethanol consumption paradigms, further corroborating a role for neuroimmune signaling in drinking behavior [14,105].…”

Section: Microglia Alcohol Activation Of Microglial Genesmentioning

confidence: 89%

The Neuroimmune Transcriptome and Alcohol Dependence: Potential for Targeted Therapies

et al. 2016

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Transcriptome profiling enables discovery of gene networks that are altered in alcoholic brains. This technique has revealed involvement of the brain's neuroimmune system in regulating alcohol abuse and dependence, and has provided potential therapeutic targets. In this review, we discuss Toll-like-receptor pathways, hypothesized to be key players in many stages of the alcohol addiction cycle. The growing appreciation of the neuroimmune system's involvement in alcoholism has also led to consideration of crucial roles for glial cells, including astrocytes and microglia, in the brain's response to alcohol abuse. We discuss current knowledge and hypotheses on the roles that specific neuroimmune cell types may play in addiction. Current strategies for repurposing US FDA-approved drugs for the treatment of alcohol use disorders are also discussed.

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“…Genetic analyses have an important role in identifying many immune-related genes associated with alcohol abuse in both rodents and humans (Kimpel et al, 2007;Liu et al, 2006;Mulligan et al, 2006). Validating several candidate genes from these studies (including Cd14, Il1ra, and Il6) through single-gene null mutations in mice confirmed that knockout of each gene resulted in decreased alcohol consumption on a two-bottle choice test (Blednov et al, 2012).…”

Section: Alcohol Glia and Neuroimmune Signalingmentioning

confidence: 91%

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

Lacagnina

Rivera

Bilbo

2016

Neuropsychopharmacol

218

170

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Drugs of abuse cause persistent alterations in synaptic plasticity that may underlie addiction behaviors. Evidence suggests glial cells have an essential and underappreciated role in the development and maintenance of drug abuse by influencing neuronal and synaptic functions in multifaceted ways. Microglia and astrocytes perform critical functions in synapse formation and refinement in the developing brain, and there is growing evidence that disruptions in glial function may be implicated in numerous neurological disorders throughout the lifespan. Linking evidence of function in health and under pathological conditions, this review will outline the glial and neuroimmune mechanisms that may contribute to drug-abuse liability, exploring evidence from opioids, alcohol, and psychostimulants. Drugs of abuse can activate microglia and astrocytes through signaling at innate immune receptors, which in turn influence neuronal function not only through secretion of soluble factors (eg, cytokines and chemokines) but also potentially through direct remodeling of the synapses. In sum, this review will argue that neural-glial interactions represent an important avenue for advancing our understanding of substance abuse disorders.

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Functional gene expression differences between inbred alcohol-preferring and –non-preferring rats in five brain regions

Cited by 107 publications

References 92 publications

Differential gene expression in the nucleus accumbens with ethanol self-administration in inbred alcohol-preferring rats

Differential gene expression in the nucleus accumbens with ethanol self-administration in inbred alcohol-preferring rats

The Neuroimmune Transcriptome and Alcohol Dependence: Potential for Targeted Therapies

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

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