BioProject

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. More...

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. Although prescribed for dyslipidemia and type-II diabetes, PPAR agonists have demonstrated therapeutic properties for several brain disorders, including alcohol dependence. PPAR agonists decrease ethanol consumption and reduce withdrawal severity and susceptibility to stress-induced relapse in rodents. However, the cellular and molecular mechanisms facilitating these properties have yet to be investigated and little is known about their effects in the brain. We tested three PPAR agonists in a continuous access two-bottle choice (2BC) drinking paradigm and found that tesaglitazar and fenofibrate decreased ethanol consumption in male C57BL/6J mice while bezafibrate did not. Hypothesizing that fenofibrate and tesaglitazar are causing brain gene expression changes that precipitate the reduction in ethanol drinking, we gave daily oral injections of fenofibrate, tesaglitazar and bezafibrate to mice for eight consecutive days and collected liver, prefrontal cortex and amygdala 24 hours after last injection. RNA was isolated and purified using MagMAX-96 Total RNA Isolation Kit. Biotinylated, amplified cRNA was generated using Illumina TotalPrep RNA Amplification Kit and hybridized to Illumina MouseWG-6 v2.0 Expression microarrays. Overall design: Mice were divided into four groups (N=10 per group): fenofibrate, tesaglitazar, bezafibrate and saline. See summary and protocols for details. Less...