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