Tyrosine hydroxylase and dopamine transporter expression in residual dopaminergic neurons: Potential contributors to spontaneous recovery from experimental Parkinsonism

1-Methyl-4-phenyl-1,2,3,6-tetrahyrdropyridine (MPTP)exposed cats develop se vere Parkinsonism that spontaneously resolves in 4-6 weeks. The present stu dy examined the extent to which compensatory changes in tyrosine hydroxylas e (TH) and dopamine transporter (DAT) gene and protein expression may under lie this behavioral recovery. In normal cats, TH and DAT protein levels wer e higher in the dorsal vs. ventral striatum. Expression of DAT and TH mRNA was higher in substantia nigra pars compacta (SNc) than in the ventral tegm ental area (VTA). In symptomatic parkinsonian animals, DAT and TH protein l evels were significantly decreased in all striatal areas studied. TH and DA T mRNA expression in residual SNc neurons were decreased a mean 32% and 38% , respectively. DAT gene expression in residual VTA neurons in symptomatic animals was decreased 30% whereas TH gene expression was unaffected. In spo ntaneously recovered cats, TH protein levels were significantly higher than the levels in symptomatic cats only in the ventral striatum, whereas no in crease in DAT protein levels were observed in any striatal area. Residual n eurons in most ventral mesencephalic regions of recovered cats had increase d TH mRNA expression but not increased DAT gene expression, compared with s ymptomatic animals. Thus, increased TH protein and mRNA and suppression of DAT protein and mRNA expression in the striatum and ventral mesencephalon w ere associated with functional recovery from MPTP-induced parkinsonism. J. Neurosci. Res. 65:254-266, 2001. (C) 2001 Wiley-Liss, Inc.