Modulation of glutamate neurotoxicity on mesencephalic dopaminergic neurons in primary cultures by the presence of striatal target cells

Glutamate toxicity was compared in substantia nigra (SN)/striatum (STR) and SN/cerebellum (CRB) co-cultures on both the entire neuronal population (ne uron specific enolase (NSE) immunopositive cells) and dopaminergic neurons (tyrosine hydroxylase (TH) immunopositive cells). In SN;CRB co-cultures NSE - and TH-positive cells were more sensitive to glutamate-induced toxicity t han in SN/STR co-cultures. Moreover, in SN/STR co-cultures as compared to S N/CRB and SN cultures, glutamate toxicity was prevented to a larger extent by TCP, a non-competitive NMDA antagonist. These results suggest that targe t cells induce a differential expression of the different glutamate recepto r subtypes in mesencephalic dopaminergic cells. Alternatively, the presence of target cells may induce the selective development of a subpopulation of dopaminergic neurons expressing predominantly NMDA receptors. (C) 2000 ISD N. Published by Elsevier Science Ltd. All rights reserved.