Glutamate receptor (GluR) channels are responsible for a number of fundamental properties of the mammalian central nervous system, including nearly all excitatory synaptic transmission, synaptic plasticity, and excitotoxin-mediated neuronal death. Although many human and rodent neuroblast cell lines are available, none has been directly shown to express GluR channels. We report here that cells from the human teratocarcinoma line NT2 are induced by retinoic acid to express neuronal N-methyl-D-aspartate (NMDA) and non-NMDA GluR channels concomitant with their terminal differentiation into neuron-like cells. The molecular and physiologic characteristics of these human GluR channels are nearly identical to those in central nervous system neurons, as demonstrated by PCR and patch damp recordings, and the cells demonstrate glutamate-induced neurotoxicity.

Caspase-3 enzyme activity is induced, and cell death follows, when cerebellar granule neurons (CGNs) from 8-day-old rats are transferred from an extracellular concentration of 25 mM K ϩ (25 mM [K ϩ

Expression of the cloned human nerve growth factor receptor (NGFR) cDNA in cell lines can generate both high-and low-affinity binding sites. Since the inability to respond appropriately to differentiation factors such as NGF may contribute to determing the malignant phenotype of neuroblastomas, we sought to determine whether the same is true of medulloblastomas. To generate a human central nervous system neuronal cell line that would respond to NGF, we infected the medulloblastoma cell line D283 MED with a defective retrovirus carrying the cDNA coding for the human NGFR. The resultant cells (MED-NGFR) expressed abundant low-and high-affinity NGFRs, and NGF treatment induced a rapid transient increase of c-fos mRNA in the NGFR-

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Previous studies indicated that Schwann cells in immature nerves express nerve growth factor (NGF) receptors, and that this expression is down regulated during development but re-induced by Wallerian degeneration. It was also shown that immature Schwann cells are induced to express galactocerebroside and other molecules characteristic of mature Schwann cells by either contact with an axon or treatment with the cyclic adenosine 3',5'-monophosphate (cAMP) analogues dibutyryl cAMP (dbcAMP) and 8-bromo cAMP or the adenylate cyclase activator forskolin. In the present study, NGF receptors on the surface of cultured Schwann cells were demonstrated by binding of an anti-rat NGF receptor monoclonal antibody or of radioiodinated NGF. Treatment of cultured Schwann cells with cAMP analogues or forskolin resulted in a progressive decrease in both immunoreactive NGF receptors and radioiodinated NGF binding. The cultured Schwann cells contained a polyadenylated RNA species homologous with human melanoma NGF receptor mRNA in sequence and size. The amount of this NGF mRNA was lower in cAMP analogue-treated than in untreated Schwann cells.