Comparative study of brain-derived neurotrophic factor messenger RNA and protein at the cellular level suggests multiple roles in hippocampus, striatum and cortex.

Brain-derived neurotrophic factor (BDNF) is important for the development and trophic support of several neuronal groups in the rat. In the present study, the distribution of BDNF messenger RNA was studied by in situ hybridization, and the cellular localization of BDNF protein was investigated with anti-peptide antibodies. Anatomical investigations were also made in animals with prolonged epileptic seizures which show an enhanced expression of BDNF messenger RNA. Major forebrain areas studied were the hippocampus, striatum and cortex. The messenger RNA coding for the putative high-affinity receptor, tyrosine kinase B, was also visualized using in situ hybridization with a probe specific for the full-length form. In the hippocampus, granule cells and pyramidal neurons expressed BDNF messenger RNA and BDNF-like immunoreactivity. Interneurons in dendritic layers did not show labelling with either method. Tyrosine kinase B messenger RNA was found within neurons in all these regions. In the medial septum-diagonal band, nucleus basalis and lateral hypothalamus, neurons with punctate cytoplasmic immunofluorescence were found, and neurons in the lateral septum were diffusely positive for BDNF. In striatum, positive labelling of medium-sized neurons was found with the antibody, whereas BDNF messenger RNA was only detectable during seizures. A laminar pattern of neuronal labelling for BDNF messenger RNA and protein was found in the neocortex. The analysis of the anatomical distribution of BDNF-producing cells suggests a number of possible cellular interactions. In the hippocampus, BDNF might act in an autocrine or paracrine manner for granule cells and pyramidal neurons, and, in addition, may serve as a signal from these principal cells to interneurons. BDNF could be a target-derived and a locally produced trophic factor for cholinergic neurons in the medial septum. The expression of BDNF in the striatum suggests that this factor could be a target-derived factor for dopaminergic neurons of substantia nigra and/or work as an autocrine/ paracrine factor within the striatum itself.