Purvalanol A, inhibitor of cyclin-dependent kinases attenuates proliferation of cells in the dentate gyrus of the adult rat hippocampus

Abstract

Several recent findings indicate that intensity of neurogenesis in adult brain might be regulated by enzymes involved in the cell cycle. Therefore, in the present study, we investigated whether the inhibition of cyclin-dependent kinases (CDKs) evoked by intraventricular administration of purvalanol A may influence the proliferation of cells in the dentate gyrus (DG) of the rat hippocampus. Purvalanol A, a selective inhibitor of CDKs, was injected into the brain lateral ventricle at concentrations of 4 nmol/3 μl or 40 nmol/3 μl. The number of proliferating cells was determined by analysis of nuclear incorporation of BrdU (100 mg/kg, ip). BrdU was given at two times points (0.5 h and 2.5 h) after vehicle or purvalanol A injection. It was found that purvalanol A given 0.5 h before BrdU injection did not cause any significant changes in the number of BrdU-positive nuclei in the DG. However, a higher dose of purvalanol A i.e. 40 nmol/3 μl given 2.5 h before BrdU administration significantly decreased the number of BrdU-positive nuclei in the DG of the hippocampus (by approximately 35%). In contrast, a lower dose of the CDKs inhibitor (4 nmol/3 μl) given at the same time point did not affect the number of BrdU-positive cells in the DG. It appears that purvalanol A inhibits the hippocampal proliferation in concentration- and time-dependent manner. Moreover, the present data indicate that CDKs are involved in generation of new cells in the adult rat hippocampus. Copyright © 2005 by Institute of Pharmacology Polish Academy of Sciences.