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 stimuli. To determine whether adult cytogenesis occurs in the intact rat striatum and to explore the possible regulatory role of psychostimulant exposure on striatal cytogenesis, immunohistochemistry with the thymidine analog bromodeoxyuridine (BrdU), a marker of DNA synthesis that labels dividing cells and their terminal progeny, was performed on the brain sections of normal adult rats and rats treated with a psychostimulant, amphetamine (AMPH). Scattered cells that incorporated BrdU were consistently seen throughout the dorsal (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, S100beta. However, none of BrdU-positive cells were found to co-localize with 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 transient 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 subventricular zone and the hippocampal dentate gyrus. However, the fraction of differentiated astrocytes was not altered 3-4 weeks after AMPH treatment. These results indicate an existence of active gliogenesis (both proliferation and differentiation) in the adult rat striatum. Vulnerability of striatal cytogenesis to psychostimulant exposure indicates a new approach to elucidate brain mechanisms responsible for addictive properties of drugs of abuse.