TRKB MESSENGER-RNA EXPRESSION IN NORMAL HUMAN BRAIN AND IN THE SUBSTANTIA-NIGRA OF PARKINSONIAN-PATIENTS - AN IN-SITU HYBRIDIZATION STUDY

trkB is a high-affinity receptor for brain-derived neurotrophic factor , a neurotrophin acting on numerous cells, including dopaminergic neur ons. Yet, little is known of its expression in the human brain. We rep ort an in situ hybridization analysis of trkB messenger RNA, encoding the catalytic form of the receptor, in the human brain post mortem. It s expression was found to be widespread but heterogenous among all the cerebral structures studied; the highest level being found int he cer ebral cortex and the cerebellum A strong bur less intense staining was observed in the striatum, nucleus basalis of Meynert, hippocampus, te gmental pedonculopontinus nucleus and substantia nigra pars compacta. Combined immunohistochemistry for tyrosine hydroxylase and in situ hyb ridization for trkB messenger RNA showed that within the substantia ni gra pars compacta a major proportion of dopaminergic neurons expressed trkB messenger RNA. Furthermore, we compared trkB messenger RNA expre ssion in the mesencephalon of six control subjects and five patients w ith Parkinson's disease, a neurodegenerative disorder characterized by a severe loss of dopaminergic neurons. Despite the fact that the numb er of trkB messenger RNA-containing neurons was dramatically reduced i n the substantia nigra pars compacta and ventral tegmental area of pat ients with Parkinson's disease, the level of trkB messenger RNA was un changed in the remaining neurons in diseased brains. These results sug gests that trkB is not involved in the process of neuronal death in Pa rkinson's disease. Furthermore, expression of brain-derived neurotroph ic factor high-affinity receptor in patients could allow this neurotro phin to be used to prevent degeneration of surviving neurons at early stages of the disease. (C) 1998 IBRO. Published by Elsevier Science Lt d.