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 (neuron 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 than in SN/STR co-cultures. Moreover, in SN/STR co-cultures as compared to SN/CRB and SN cultures, glutamate toxicity was prevented to a larger extent by TCP, a non-competitive NMDA antagonist. These results suggest that target cells induce a differential expression of the different glutamate receptor 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.
Mateu
G
G
INSERM U336, Ecole Nationale Supérieure de Chimie, 8 rue de l'Ecole Normale, 34296 Cedex 5, Montpellier, France. gmateu@cit.enscm.fr
Privat
A
A
Thibault
J
J
Vignon
J
J
D000818:Animals; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D002713:Chlorine; D018920:Coculture Techniques; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000633:toxicity*; D007150:Immunohistochemistry; D007455:Iodine; D007928:Lethal Dose 50; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000494:pharmacology; D010636:Phenols; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D012459:Salicylates; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D004338:Drug Combinations; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D010636:Phenols; D012459:Salicylates; D018698:Glutamic Acid; D002713:Chlorine; C030307:TCP (antiseptic); C012058:tenocyclidine; D007455:Iodine; D014446:Tyrosine 3-Monooxygenase; D010751:Phosphopyruvate Hydratase; D010622:Phencyclidine; D004298:Dopamine