Differential neurotoxicity induced by l-DOPA and dopamine in cultured striatal neurons
1996; Elsevier BV; Volume: 743; Issue: 1-2 Linguagem: Inglês
10.1016/s0006-8993(96)01056-6
ISSN1872-6240
AutoresNeng‐neng Cheng, Takehiko Maeda, Toshiaki Kume, Satoshi Kaneko, Hanae Kochiyama, Akinori Akaike, Yoshio Goshima, Yoshimi Misu,
Tópico(s)Neuroscience and Neural Engineering
ResumoThe 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 a non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and by an NMDA receptor antagonist, MK-801. Neither antagonist prevented 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.
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