Tissue distribution of neurturin, persephin and artemin in the human brainstem at fetal, neonatal and adult age

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.