Research Report Tissue distribution of neurturin, persephin and artemin in the human brainstem at fetal, neonatal and adult age Marina Quartu, Maria Pina Serra, Marianna Boi, Natascia Sestu, Maria Letizia Lai, Marina Del Fiacco ⁎ Department of Cytomorphology, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, Italy ARTICLE INFO ABSTRACT Article history: Accepted 17 January 2007 Available online 26 January 2007 The occurrence of the glial cell line-derived neurotrophic factor (GDNF) family ligands neurturin (NTN), persephin (PSP), and artemin (ART) was examined by immunohistochemistry in the normal human brainstem at pre-, perinatal and adult age. Immunolabelled neurons were unevenly distributed and each trophin had a consistent distribution pattern. As a rule, the NTN antiserum produced the most abundant and diffuse tissue labelling, whereas the lowest density of positive elements was observed after ART immunostaining. Labelling for NTN, PSP, and ART occurred at all examined ages. For each trophin, neuronal perikarya were observed within sensory and motor nuclei of cranial nerves, dorsal column nuclei, olivary nuclear complex, reticular formation, pontine nuclei, locus caeruleus, raphe nuclei, substantia nigra, and quadrigeminal plate. Nerve fibers occurred within gracile and cuneate fasciculi, trigeminal spinal tract and nucleus, oculomotor and facial nerves, solitary tract, vestibular nerve, medial longitudinal fasciculus, medial and lateral lemnisci, and inferior and superior cerebellar peduncles. Age changes were detected in the distribution pattern for each trophin. On the whole, in the grey matter, labelled perikarya were more frequently observed in pre- and perinatal than in adult specimens; on the other hand, in discrete regions, nerve fibers and terminals were abundant and showed a definite arrangement only in adult tissue; finally, distinct fiber systems in the white matter were immunolabelled only at pre- and perinatal ages. The results support the concept of a trophic involvement of NTN, PSP, and ART in the development, functional activity and maintenance of a variety of human brainstem neuronal systems. © 2007 Elsevier B.V. All rights reserved. Keywords: GDNF-family trophin Man Medulla oblongata Pon Mesencephalon Immunohistochemistry 1. Introduction Neurturin (NTN) (Kotzbauer et al., 1996), persephin (PSP) (Milbrandt et al., 1998), and artemin/neublastin (ART) (Baloh et al., 1998), distant members of the transforming growth factor-β superfamily, are structurally related trophic proteins belonging to the glial cell line-derived neurotrophic factor (GDNF) family. They all signal through a tyrosine kinase receptor system consisting of one of the four selective ligand binding components, named GFRalpha-1 to -4, and the transmembrane tyrosine kinase protein Ret (Airaksinen and Saarma, 2002). Experimental data indicate that GDNF family ligands exert similar biological activities in different neuronal systems, which require them for survival, differentiation and BRAIN RESEARCH 1143 (2007) 102 – 115 ⁎ Corresponding author. Fax: +39 070 6754003. E-mail address: dfiacco@unica.it (M. Del Fiacco). 0006-8993/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2007.01.065 available at www.sciencedirect.com www.elsevier.com/locate/brainres