Long-term behavioral recovery in Parkinsonian rats by triple transduction with dopamine-biosynthesizing enzyme genes / 中华神经科杂志

ABSTRACT

Objective To observe the effect of gene therapy for Parkinson disease by triple transduction with dopamine-biosynthesizing enzyme genes. Methods We constructed high titer purified adeno-associated virus (AAV) vectors containing cDNAs encoding human tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC) and GTP cyclohydrolase I (GCH) respectively. AAV-TH, AAV-AADC and AAV-GCH were stereotaxically injected into the denervated striatum of Parkinsonian rat; the expression of TH, AADC or GCH was assayed by using immunohistochemical staining; the rotational behavior was assayed for 1 year.Results The immunohistochemical staining and behavioral testing showed that all of TH, AADC and GCH were expressed stably in the striatum, and the rats treated with AAV-TH, AAV-AADC and AAV-GCH showed more remarkable decrease in rotation rate persisted for at least 1 year, than those treated with AAV-TH and AAV-AADC(P