The localization and functional contribution of striatal aromatic L-amino acid decarboxylase to L-3,4-dihydroxyphenylalanine decarboxylation in rodent parkinasonian models

L-3,4-Dihydroxyphenylalanine (L-dopa) is the mainstay of therapy for patien ts with Parkinson's disease (PD), and mediates its primary effects through conversion into dopamine by aromatic L-amino acid decarboxylase (AADC). Giv en the loss of AADC-containing nigrostriatal dopaminergic neurons in PD, ho wever, the location of residual AADC that converts L-dopa into dopamine rem ains controversial. The first objective of this study was to establish the presence of AADC expression in striatal neurons and glia using reverse tran scriptase and PCR. Transcripts for the neuronal but not nonneuronal forms o f AADC were detected in striatal tissue, cultured striatal neurons, and gli a. We then examined whether this striatal AADC expression represents a phys iologically significant source of dopamine production. No dopamine release was detected following incubation of striatal cultures with L-dopa or trans duction with adenovirus expressing tyrosine hydroxylase. Out data establish the presence of AADC expression in the striatum both in vivo and in vitro, but suggest that striatal components do not represent a primary source of L-dopa decarboxylation following nigrostriatal denervation in rats. Underst anding the source and localization of AADC is important in understanding th e complications of L-dopa therapy and in designing rational therapeutic str ategies for PD, including cellular transplantation and gene therapy.