Human NT2 neurons express a large variety of neurotransmission phenotypes in vitro

The NT2 cell Line, which was derived from a human teratocarcinoma, exhibits properties that are characteristic of a committed neuronal precursor at an early stage of development NT2 cells can be induced by retinoic acid to di fferentiate in vitro into postmitotic central nervous system (CNS) neurons (NT2-N cells). The commitment of NT2-N cells to a stable neuronal phenotype is irreversible. Because it may be possible to transplant these human neur ons to compensate for neuronal loss after traumatic injuries or neurodegene rative diseases of the CNS, knowledge of their phenotype is essential. This study aimed to characterize in detail the neurotransmission phenotype of N T2-N cells by using immunocytochemical methods. Single peroxidase immunosta ining demonstrated that NT2-N cells expressed the gamma-aminobutyric acider gic (GABAergic), catecholaminergic, and cholinergic phenotypes to a large e xtent and expressed the serotonergic phenotype to a minor extent. NT2-N cel ls also expressed different neuropeptides, such as neuropeptide Y, oxytocin , vasopressin, calcitonin gene-related peptide, and Met- and Leu-enkephalin . Double fluorescence immunostaining further indicated that a large number of NT2-N cells could express GABA and another neurotransmitter or neuropept ide at the same time. Finally, electron microscopy demonstrated that these NT2 neurons elaborate classical synaptic contacts. The multipotentiality of these neurons, combined with their apparent functionality, suggests that t hey may represent useful material for a variety of therapeutic approaches a imed at replacing dead neurons after neurodegenerative diseases or lesions of the CNS. J. Comp. Neurol. 422:380-395, 2000. (C) 2000 Wiley-Liss, Inc.