Comparison of neurotrophin regulation of human and rat neuropeptide Y (NPY) neurons: induction of NPY production in aggregate cultures derived from rat but not from human fetal brains

摘要: Previous studies established that brain-derived neurotrophic factor (BDNF) induces neuropeptide Y (NPY) production and accumulation of NPY-mRNA in cultures rat fetal brain tissues. In this study, we addressed the question: Are cultured human NPY neurons regulated by BDNF and/or another member neurotrophin (NT) family growth factors? Using aggregate derived from cortical hemispheres, assessed effect on varying following experimental conditions: culture age; medium composition (with without serum), dose duration exposure to BDNF, species tested (BDNF, NT-4/5, NT-3 or NGF). Under none these conditions did NGF induce an increase production. This was contrast forskolin + phorbol 12 myristate 13-acetate (PMA) which were highly effective inducing production, verifying expression is a process cultures. None neurotrophins enhanced response PMA. By comparison, using cortices, NT-4/5 equipotent but essentially ineffective. Moreover, effects PMA additive, indicating involvement distinct intracellular signalling pathways. Western blot analyses human- rat-derived aggregates indicated presence full-length Trk receptors are tyrosine-phosphorylated either NT-3. Primary astrocytes (rat as well human) devoid functional TrkB receptor, strongly suggesting neuronal aggregates. Thus, receptor expressed both aggregates, only responded NT-4/5. These results consistent with difference post TrkB-receptor event(s) mediating action neurons.