Distinct populations of hypothalamic dopaminergic neurons exhibit differential responses to brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3)

We have previously demonstrated that differentiation of hypothalamic dopami nergic (DA) neurons can be induced in culture by their pituitary intermedia te lobe target cells, through both membrane and diffusible factors. We also showed that subpopulations of DA neurons from the arcuate nucleus only, no t the periventricular area, can respond to the target. Here we investigated the possibility that both neuronal subsets could also respond differential ly to brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT3). Add ition of NT3, but not BDNF, enhanced growth and branching of neurites, tyro sine hydroxylase (TH) as well as increasing levels of cultured arcuate DA n eurons. Conversely, BDNF, but not NT3, affected the same parameters in cult ured periventricular DA neurons. The neurotrophins thus affect DA neurons i n a structure and neuronal type-selective manner, since general neuronal ma rkers were not affected by either neurotrophin. Neurotrophin effects were r eversed by addition of specific antibodies directed against them or their r espective receptors, TrkB or TrkC. By themselves, the antibodies inhibited development of DA neurons below that of control cultures, suggesting involv ement of endogenous neurotrophins. BDNF and NT3 were indeed found in both a rcuate and periventricular neurons and in the intermediate lobe. BDNF was a lways present as the mature peptide. The mature form of NT3 was only detect ed in the periventricular area; a precursor-like heavier form was present i n all tissues studied. The present data suggest that NT3, but not BDNF, cou ld participate in the differentiating action of intermediate lobe cells on arcuate DA neurons.