6-hydroxydopamine Induces Neuronal Apoptosis in Mouse Cortical Cell Cultures.
- Author:
Jae Houn JUNG
1
;
Hyo Jung KANG
;
Seonghyang SOHN
;
Young Ki CHUNG
;
Byoung Joo GWAG
;
Jai Sung NOH
Author Information
1. Department of Psychiatry and Behavioral Sciences, Institute for Medical Sciences, Ajou University, School of Medicine, Suwon, Korea.
- Publication Type:Original Article
- Keywords:
6-hydroxydopamine;
Parkinson's disease;
Cell death;
Apoptosis;
Antioxidants
- MeSH:
Animals;
Antioxidants;
Apoptosis*;
Caspase Inhibitors;
Cell Culture Techniques*;
Cell Death;
Cell Membrane;
Chromatin;
Coculture Techniques;
Cycloheximide;
Dizocilpine Maleate;
DNA Fragmentation;
Dopaminergic Neurons;
Excitatory Amino Acid Antagonists;
Mice*;
Neocortex;
Neuroglia;
Neurons*;
Nuclear Envelope;
Oxidative Stress;
Oxidopamine*;
Parkinson Disease
- From:Journal of Korean Neuropsychiatric Association
2000;39(3):656-665
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
OBJECTIVES: We examined the patterns of cell death induced by the 6-hydroxydopamine, a selective dopaminergic toxin that used to produce Parkinson's disease model. METHOD: Neocortices from 14- or 15-day-old fetal mice for neuron-glia co-cultures were used for this experiments. RESULTS: Cortical cell cultures exposed to 10-100 microM 6-hydroxydopamine for 24 hr under-went neuronal death without injuring glia. The degenerating neurons showed hallmark of apoptosis featuring cell body shrinkage, nuclear chromatin condensation and aggregation, nuclear membrane disintegration with intact plasma membrane, and prominent internucle- osomal DNA fragmentation. Neither the glutamate antagonists (10 microM MK-801 and 50 microM CNQX) nor antioxidants (trolox, 100 microM, N-acetyl-cysteine, 100 microM) prevented the 6-OHDA induced neuronal injury. The death was attenuated by addition of two different anti-apoptotic agents, 1 microgram/ml cycloheximide and caspase inhibitor (100 microM zVAD-fmk). CONCLUSION: These features suggest that 6-OHDA induced apoptotic type of neuronal death in cortical neuronal culture. Considering the protective effect of caspase inhibitors, a mechanism involving caspase cascade rather than oxidative stress is responsible for the 6-OHDA-induced neuronal apoptosis. In addition, our results showed that 6-OHDA-induced apoptosis is not confined to dopaminergic neurons and the primary cortical culture system so this system is suitable for the study of 6-OHDA-induced neuronal apoptosis.
