The localization and functional contribution of striatal aromatic L-amino acid decarboxylase to L-3,4-dihydroxyphenylalanine decarboxylation in rodent parkinsonian models.
L-3,4-Dihydroxyphenylalanine (L-dopa) is the mainstay of therapy for patients with Parkinson's disease (PD), and mediates its primary effects through conversion into dopamine by aromatic L-amino acid decarboxylase (AADC). Given the loss of AADC-containing nigrostriatal dopaminergic neurons in PD, however, the location of residual AADC that converts L-dopa into dopamine remains controversial. The first objective of this study was to establish the presence of AADC expression in striatal neurons and glia using reverse transcriptase and PCR. Transcripts for the neuronal but not nonneuronal forms of AADC were detected in striatal tissue, cultured striatal neurons, and glia. We then examined whether this striatal AADC expression represents a physiologically significant source of dopaine production. No dopamine release was detected following incubation of striatal cultures with L-dopa or transduction with adenovirus expressing tyrosine hydoxylase. Our 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. Understanding the source and localization of AADC is important in understanding the complications of L-dopa therapy and in designing rational therapeutic strategies for PD, including cellular transplantation and gene therapy.
Nakamura
K
K
Department of Neurology, Pharmacological & Physiological Sciences, The University of Chicago, IL 60637, USA.
Ahmed
M
M
Barr
E
E
Leiden
J M
JM
Kang
U J
UJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D018929:Cell Culture Techniques; D003342:Corpus Striatum / Q000166:cytology / Q000201:enzymology*; D003653:Decarboxylation; D004296:Dopa Decarboxylase / Q000235:genetics / Q000502:physiology*; D004298:Dopamine / Q000096:biosynthesis*; D005260:Female; D015316:Genetic Therapy; D007980:Levodopa / Q000378:metabolism*; D009457:Neuroglia / Q000201:enzymology; D010300:Parkinson Disease / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D004296:Dopa Decarboxylase; D004298:Dopamine