Takehiko Maeda, Masakazu Ibi, Seiichiro Shimazu and Akinori Akaike (*)
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
(*) To whom correspondence should be addressed.
Abstract: We examined the role of striatal cells in cytotoxicity induced by N-methyl-D-aspartate (NMDA) in dopamine (DA) neurons in rat mesencephalic slice culture. Coronal sections were prepared from 2- and 3-day-old rat brains and cultured using the interface culture method for 2 - 3 weeks before the NMDA cytotoxicity experiment. The exposure of mesencephalic cultures without striatum (single culture) to NMDA (10 - 300 microM) for 24 hr reduced the number of DA neurons in a concentration-dependent manner. The co-administration of the non-competitive NMDA-receptor antagonist significantly inhibited the neurotoxic effect of NMDA. When mesencephalon and striatum were kept in contact and co-cultured (contacting co-cultures), the growth of DA fibers into the striatal part was observed. In the contacting co-cultures with striatum, the minimal effective concentration for NMDA cytotoxicity was higher than that in single cultures. The contacting co-cultures with cerebellum did not alter the NMDA cytotoxicity. When the mesencephalon and striatum slices were kept apart and co-cultured, the co-cultures showed neither an outgrowth of DA fibers to the striatum nor any effect on the NMDA cytotoxicity. These results suggest that the projection of rat mesencephalic DA neurons to the striatum attenuates the NMDA cytotoxicity in DA neurons themselves.
Keywords: Dopaminergic neuron, Mesencephalon, Neuronal death, N-methyl-D-aspartate, Slice culture