Abstract
The neurotoxicity of L-DOPA and dopamine (DA) on striatal neurons was examined by using primary cultures of rat striatum. Exposure to L-DOPA and DA at concentrations of 30-300 μM induced dose-dependent cell death in both younger cultures (3 days in culture, 3 DIC) and elder cultures (10 days in culture, 10 DIC). The cytotoxicity of L-DOPA and DA was also dependent on the exposure time (6-24 h). Ascorbic acid (200 μM) inhibited both L-DOPA- and DA-induced cytotoxicity in 3 DIC cultures, whereas it provided significant protection against DA- but not L-DOPA-induced cytotoxicity in 10 DIC cultures. The L-DOPA cytotoxicity in 10 DIC cultures was prevented by an non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and by an NMDA receptor antagonist, MK-801. Neither antagonist prevened DA cytotoxicity. D-DOPA did not affect the viability of 10 DIC cultures, though it elicited marked toxicity in 3 DIC cultures. These results suggest that there are two components in the mechanisms that mediate the L-DOPA neurotoxicity on striatal neurons: One is autoxidation-relevant and the other is autoxidation-irrelevant. With respect to the latter, glutamate receptor stimulation may be involved. In contrast, autoxidation plays an important role in DA neurotoxicity.
Original language | English |
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Pages (from-to) | 278-283 |
Number of pages | 6 |
Journal | Brain Research |
Volume | 743 |
Issue number | 1-2 |
DOIs | |
State | Published - 1996 |
Keywords
- L-DOPA
- ascorbic acid
- autoxidation
- dopamine
- glutamate
- neurotoxicity
- striatum
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- Clinical Neurology
- Developmental Biology