Brain-derived neurotrophic factor and neurotrophin-3 mRNAs are expressed in ventral midbrain regions containing dopaminergic neurons

Abstract Recent evidence suggests that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) enhance the survival of ventral mesencephalic dopaminergic neurons. In this study, cellular distributions of mRNAs for the nerve growth factor (NGF) family of neurotrophins (NGF, BDNF, and NT-3) and the catecholamine biosynthetic enzyme tyrosine hydroxylase (TH) were evaluated in the ventral mesencephalon of adult rat to determine if the neurotrophins are synthesized in regions of the responsive dopaminergic cells. Messenger RNAs were localized by in situ hybridization of 35 S-labeled cRNA probes and emulsion autoradiography. Neurotrophin-3 cRNA labeled neurons in the ventral tegmental area, medial substantia nigra pars compacta, and retrorubral field. The distributions of NT-3 mRNA-containing and TH mRNA-containing neurons corresponded very well in these areas. Hybridization of the BDNF cRNA labeled scattered cells in corresponding fields of TH mRNA-containing neurons in both the ventral tegmental area and the medial substantia nigra pars compacta but, in contrast to NT-3 cRNA, labeled fewer cells in these areas. Somata containing BDNF mRNA were also present in surrounding regions, including the interfascicular and interpeduncular nuclei, the supramammillary region, the periaqueductal grey matter, and fields dorsal to the lateral substantia nigra. Hybridization of NGF cRNA was not observed in the ventral mesencephalon. These results demonstrate that mRNAs for NT-3 and BDNF are expressed by neurons in both the substantia nigra and ventral tegmental area of adult rat and suggest that trophic support for the dopaminergic neurons in these areas may arise from local synthesis. Moreover, these results raise the possibility that perturbations in local neurotrophin synthesis might contribute to dopamine-related disorders including Parkinson's disease and schizophrenia.