NT-4 mRNA and protein in the central nervous sytem of Nothobranchius furzeri

Neurotrophin-4 (NT-4) is a member of the nerve growth factor family, and is structurally and functionally related to other neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and the fish specific neurotrophin-6 (NT-6). Neurotrophins share approximately 50% homology in amino acid sequences and are known to have individual functions in limited regions and at specific ages. The molecular phylogeny of neurotrophin sequences suggests that the duplication of neurotrophins ancestor genes, occurred in fish, led to the formation of NT-4/5 and BDNF from an intermediate ancestor. NT-4, as all other neurotrophins, interact with two distinct receptors: TrkB, high affinity receptor, and p75 low-affinity receptor (p75NTR). In the present survey, we identified and cloned the gene encoding NT-4 in the teleost N. furzeri, a model spe- cies for aging research. We studied the neuroanatomical localization of NT-4 mRNA and protein in the whole brain of adult specimens, respectively by in situ hybridization and immunohistochemistry. NT-4 mRNA was abundantly and diffusely expressed in the telencephalon, and sparsely or in restricted areas of diencephalon, mesencephalon and rhomboencephalon. NT-4 protein was localized in few neurons of the telencephalon, in some nuclei of diencephalon, and in restricted areas of mesencephalon and rhomboencephalon. The neuroanatomical survey demonstrates that NT-4 is present in the adult brain of teleost N. furzeri, and mRNA and protein are differently distributed. These differ- ences could indicate that the site of synthesis of NT-4 might not be the site of action.