Effects of gliosis on dopamine metabolism in rat striatum

Abstract

Neuroimplantation is inevitably accompanied by gliosis. Although graft-induced trophic effects on host neurons may be mediated by glial cells, the effects of gliosis on dopamine (DA) metabolism remains unclear. To examine these effects, basic fibroblast growth factor (bFGF) was directly infused into the striatum of 12 male rats (250–280 g). One week later, substantial gliosis was demonstrated in the infused striatum by immunochemical staining for glial fibrillary acidic protein (GFAP) and quantified by GFAP Western blot analysis. One week after bFGF infusion, extracellular DA and its metabolites were measured by in vivo microdialysis using HPLC. Infusion of l-DOPA through the dialysis probe resulted in a 60% reduction in the l-DOPA-induced DA peak in the gliotic striatum compared with the normal side. After l-DOPA infusion, dihydroxyphenylacetic acid (DOPAC) levels were similar between the gliotic and normal striatum. In contrast, homovanillic acid (HVA) levels were 26% higher in the gliotic striatum. Enzyme assays demonstrated that aromatic l-amino acid decarboxylase activity was unchanged in the gliotic striatum, but both MAO-A and MAO-B activities increased by 23% and 21%, respectively. These results suggest that the reduced striatal DA peak in the gliotic striatum after l-DOPA administration was due to accelerated DA catabolism through enhanced MAO activity. The bFGF-induced striatal gliosis may serve as a model to study neurotransmitter metabolism in the gliotic brain caused by disease processes, aging, or tissue grafting.