Tyrosine kinase B messenger RNA expression in normal human brain and in the substantia nigra of parkinsonian patients: an in situ hybridization study

Abstract

Tyrosine kinase B is a high-affinity receptor for brain-derived neurotrophic factor, a neurotrophin acting on numerous cells, including dopaminergic neurons. Yet, little is known of its expression in the human brain. We report an in situ hybridization analysis of tyrosine kinase B messenger RNA, encoding the catalytic form of the receptor, in the human brain post mortem. Its expression was found to be widespread but heterogenous among all the cerebral structures studied, the highest level being found in the cerebral cortex and the cerebellum. A strong but less intense staining was observed in the striatum, nucleus basalis of Meynert, hippocampus, tegmental pedonculopontinus nucleus and substantia nigra pars compacta. Combined immunohistochemistry for tyrosine hydroxylase and in situ hybridization for tyrosine kinase B messenger RNA showed that within the substantia nigra pars compacta a major proportion of dopaminergic neurons expressed tyrosine kinase B messenger RNA. We compared tyrosine kinase B messenger RNA expression in the mesencephalon of six control subjects and five patients with Parkinson's disease, a neurodegenerative disorder characterized by a severe loss of dopaminergic neurons. Despite the fact that the number of tyrosine kinase B messenger RNA-containing neurons was dramatically reduced in the substantia nigra pars compacta and ventral tegmental area of patients with Parkinson's disease, the level of tyrosine kinase B messenger RNA was unchanged in the remaining neurons in diseased brains. These results suggests that tyrosine kinase B is not involved in the process of neuronal death in Parkinson's disease. Furthermore, expression of brain-derived neurotrophic factor high-affinity receptor in patients could allow this neurotrophin to be used to prevent degeneration of surviving neurons at early stages of the disease.