Intrastriatal injection of dopamine results in DNA damage and apoptosis in rats
作者:
Akinori Hattori,
Yongquan Luo,
Hiroyuki Umegaki,
James Munoz,
George Roth,
期刊:
NeuroReport
(OVID Available online 1998)
卷期:
Volume 9,
issue 11
页码: 2569-2572
ISSN:0959-4965
年代: 1998
出版商: OVID
关键词: Apoptosis;DNA fragmentation;Dopamine neurotoxicity;Striatum;Neurodegeneration;Terminal deoxynucleotidyl transferase
数据来源: OVID
摘要:
OVERFLOW of the neurotransmitter dopamine (DA) in striatum is implicated in the neurodegenerative processes in ischemia, hypoxia and local exposure to high concentrations of excitatory amino acids. However, how DA causes neurotoxicity is not understood. We report that intrastriatal injection of DA (0.5–1 μmol/μl) in Wistar rats produces a robust increase in apoptotic cell death as determined by both a terminal deoxynucleotidyl transferase catalyzed dUTP-biotin nick labeling (TUNEL) and Klenow polymerase catalyzed [32P]dCTP labeled DNA ladder. Cells in which apoptosis was induced by DA are characterized by condensed chromatin, DNA fragmentation, shrinkage and irregular shapes. The apoptotic cell death induced by DA is not due to the effect of hyperosmolar solution since intrastriatal injection of identical concentrations of NaCl on opposite sides of the same rat brains shows little TUNEL-positive labeling. The number of apoptotic cells is proportional to the amount of DA and length of exposure period. With DA concentrations from 0 to 1 μmol/μl, the maximal toxic effect appears at a concentration of 1 μmol/μl after 24 h exposure. Demonstration of DA-induced apoptosisin vivomay provide a potential molecular mechanism for DA neurotoxicity.
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