Gemfibrozil increases the specific binding of rat-cortex nuclear extracts to a PPRE probe.

PPAR agonists have been shown to elicit beneficial responses in several cell- and tissue-models of neurotoxicity. To determine if brain PPARs are responsive to the in vivo administration of PPAR agonists in a similar way to those receptors present in other anatomical localizations, such as liver, we fed rats with gemfibrozil incorporated in the diet at a dose that activates hepatic PPARalpha and produces its typical hypolipidemic effect. Rat cortex nuclear extracts presented a pattern of two specific shifted bands when incubated with a PPRE oligonucleotide. Samples from gemfibrozil-treated rats showed a significant increase in the intensity of the two shifted bands regarding control values (2.4- and 1.8-fold for the specific bands 1 and 2, respectively), indicating that orally administered gemfibrozil reaches brain tissues at concentrations sufficient to increase the specific binding of cortex nuclear extracts to an oligonucleotide mimicking a bona fide PPRE, although no changes in cortex ACO mRNA levels were produced.