Gliogenesis in the striatum of the adult rat: alteration in neural progenitor population after psychostimulant exposure

Cytogenesis from proliferating progenitor cells is present in the rat brain throughout adulthood, and is regulated by a variety of environmental stimu li. To determine whether adult cytogenesis occurs in the intact rat striatu m and to explore the possible regulatory role of psychostimulant exposure o n striatal cytogenesis, immunohistochemistry with the thymidine analog brom odeoxyuridine (BrdU), a marker of DNA synthesis that labels dividing cells and their terminal progeny, was performed on the brain sections of normal a dult rats and rats treated with a psychostimulant, amphetamine (AMPH). Scat tered cells that incorporated BrdU were consistently seen throughout the do rsal (caudate putamen) and ventral (nucleus accumbens) striatum 24 h after BrdU injection. Three to four weeks after BrdU injection, approximately 10- 20% of surviving newborn cells differentiated into astroglia. according to their radial morphology of glia and co-expression of an astroglial marker, S100 beta. However, none of BrdU-positive cells were found to co-localize w ith a neuronal marker, neuronal nuclear antigen (NeuN). Acute injection of AMPH at a behaviorally active dose (10 mg/kg, i.p.) produced a rapid and tr ansient decrease in the number of BrdU-labeled cells in both the dorsal (70 .6% of control) and ventral (66.7% of control) striatum, but not in the sub ventricular zone and the hippocampal dentate gyrus. However, the fraction o f differentiated astrocytes was not altered 3-4 weeks after AMPH treatment. These results indicate an existence of active gliogenesis (both proliferat ion and differentiation) in the adult rat striatum. Vulnerability of striat al cytogenesis to psychostimulant exposure indicates a new approach to eluc idate brain mechanisms responsible for addictive properties of drugs of abu se. (C) 2001 Elsevier Science B.V. All rights reserved.