Excitotoxicity plays a role in the death of tyrosine hydroxylase- immunopositive nigral neurons cultured in serum-free medium.
We studied the effects of different amino acid receptor antagonists and a calcium (Ca2+) channel blocker on the survival of embryonic tyrosine hydroxylase (TH)-immunopositive nigral neurons grown under serum-free culture conditions. Ventral mesencephalic neurons were cultivated for 2 or 7 days. Following serum withdrawal on day 2, some cultures were treated with different concentrations of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine hydrogen maleate (MK-801), the competitive NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid, the competitive kainate/quisqualate receptor antagonist 6,7-dinitroquinoxaline-2, 3-dione, and the Ca2+ channel blocker flunarizine. Treatment with MK-801 or flunarizine increased the survival of TH-positive neurons after serum deprivation. These findings suggest a possible role for excitotoxicity in dopaminergic cell death which can be prevented by blocking the NMDA receptor or by inhibiting Ca2+ entry through voltage-gated channels.
Schierle
G S
GS
Section for Neuronal Survival, Wallenberg Neuroscience Center, Department of Physiology and Neuroscience, University of Lund, Sölvegatan 17, Lund, S-223 62, Sweden.
Brundin
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004622:Embryo, Mammalian; D005444:Flunarizine / Q000494:pharmacology; D008636:Mesencephalon / Q000166:cytology* / Q000201:enzymology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009498:Neurotoxins / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D015763:2-Amino-5-phosphonovalerate; D002121:Calcium Channel Blockers; D016895:Culture Media, Serum-Free; D016291:Dizocilpine Maleate; D005444:Flunarizine; D009498:Neurotoxins; D011810:Quinoxalines; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D014446:Tyrosine 3-Monooxygenase; C056723:FG 9041