The vulnerability of nigral neurons to Parkinson's disease is unrelated totheir intrinsic capacity for dopamine synthesis: An in situ hybridization study

The contribution of the dopamine-synthetic capacity of nigral neuronal subr egions to their vulnerability to degeneration in idiopathic Parkinson's dis ease (IPD) was explored using semiquantitative in situ hybridization to stu dy expression of mRNA, the the rate-limiting dopamine synthetic enzyme, tyr osine hydroxylase (TH). Expression of mRNA. the structural protein, beta-tu bulin, and the glycolytic enzyme, fructose-1,6, biphosphate aldolase (aldol ase C) was studied in parallel in individual neurons of the substantia nigr a pars compacta (SNc) in marched groups of IPD and control subjects. TH mRN A expression was found to be heterogeneously expressed in nigral neurons in control and IPD subjects. There was no significant difference in mean valu es for TH mRNA expression between control and IPD cases and none between ni gral subregions, either in control subjects or in established TPD subjects in this study, but there was evidence for a selective upregulation of TH mR NA expression in nonmelanized neurons in IPD. There was no relationship bet ween TH mRNA expression disease duration or L-dopa dosage in the IPD group, Mean TH mRNA values for two additional 40-year-old control subjects fell w ithin the range of values of the aged-control group. Aldolase C and beta-tu bulin expression did not differ between control and IPD groups or between n igral subregions. These findings suggest that regulation of dopamine synthesis at the level o f the cell body does not play a part in determining the pattern of nigral c ell vulnerability in IPD. The heterogeneous pattern of TK synthesis was not age-dependent and may be of physiological significance in nigral function. There was no evidence for compensatory upregulation of TH synthesis in sur viving melanized neurons in IPD but non-meIanized neurons may be involved i n this process. Surviving nigral neurons in IPD appear to retain the capaci ty for normal aldolase C and beta-tubulin peptide synthesis, Long-term L-do pa treatment does not appear to compromise normal function of nigral dopami nergic neurons.