[Factors regulating survival and death of midbrain dopamine neurons].
We utilized organotypic midbrain slice cultures for the assessment of survival and degeneration of dopaminergic neurons in the substantia nigra. Application of N-methyl-D-aspartate (NMDA) to midbrain slice cultures for 24 h caused a concentration-dependent decrease in the number of surviving dopaminergic neurons visualized by tyrosine hydroxylase immunohistochemistry. Simultaneous application of (-)-deprenyl significantly attenuated the cytotoxic effect of NMDA. Because pretreatment with (-)-deprenyl failed to reduce NMDA toxicity, it is suggested that the neuroprotective effect of (-)-deprenyl is not mediated by its irreversible inhibitory action on monoamine oxidase B. We also prepared co-cultures of midbrain and striatal slices to investigate whether the presence of target tissue influences toxic actions of several drugs on dopaminergic neurons. Co-cultured dopaminergic neurons formed dense innervation to the striatal tissue. Dopaminergic neurons in midbrain--striatum co-cultures were more resistant to the cytotoxic actions of NMDA and a nitric oxide donor NOC-18, than the same neuronal population in single midbrain cultures. On the other hand, the toxicity of 1-methyl-4 phenylpyridinium ion or buthionine-[S,R]-sulfoximine was more prominent in midbrain--striatum co-cultures than that in single midbrain cultures. Organotypic slice cultures appeared to be a useful system for evaluation of dopaminergic neuronal death under experimental conditions relevant to physiological/pathophysiological situations.
Katsuki
H
H
Department of Pharmacology and Neuropharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Kume
T
T
Kaneko
S
S
Akaike
A
A
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D016923:Cell Death; D046508:Culture Techniques; D004298:Dopamine / Q000032:analysis*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008995:Monoamine Oxidase / Q000032:analysis; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D012642:Selegiline; D019328:Buthionine Sulfoximine; D016202:N-Methylaspartate; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine