Up-regulation of tyrosine hydroxylase mRNA in a sub-population of A10 dopamine neurons in Parkinson's disease

Neuronal injury has been consistently found in A10 midbrain dopamine neuron s in Parkinson's disease (PD). To assess changes in neurotransmitter-relate d gene transcription, in these neurons in PD, tyrosine hydroxylase (TH) mRN A expression was examined in the ventral tegmental area (VTA) of seven PD c ases and seven control subjects, using in situ hybridization histochemistry (ISHH). In controls, TH mRNA expression was found in both melanised and no n-melanised neurons in the VTA. Neither population expressed dopamine beta- hydroxylase (DBH). Of the melanised neurons, 99% were TH mRNA positive. The level of the TH mRNA signal (expressed as grain density per cell) was simi lar in the two populations (melanised: 0.129+/-0.003 (mean+/-S.E.M.). n=142 vs, non-melanised: 0.138+/-0.006, n=89, P>0.05, Student's t-Test). In PD c ases there was no significant change in TH mRNA expression in melanised neu rons (0.138+/-0.003, n=196), and the proportion of positively labeled melan ised neurons was 98%. However, non-melanised neurons showed significantly h igher TH mRNA (0.163+/-0.006, n =87) than non-melanised neurons in control subjects (P<0.005) and melanised neurons in the PD cases (P<0.0005). This u p-regulation of TH mRNA expression in non-melanised neurons may suggest the existence of a compensatory mechanism at presynaptic level. (C) 2000 Elsev ier Science B.V. All rights reserved.