Premium
Formation of the Base Modification 8‐Hydroxyl‐2′ ‐ Deoxyguanosine and DNA Fragmentation Following Seizures Induced by Systemic Kainic Acid in the Rat
Author(s) -
Lan Jing,
Henshall David C.,
Simon Roger P.,
Chen Jun
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0740302.x
Subject(s) - kainic acid , tunel assay , dna fragmentation , piriform cortex , striatum , dna damage , hippocampus , terminal deoxynucleotidyl transferase , temporal cortex , 8 hydroxy 2' deoxyguanosine , deoxyguanosine , chemistry , fragmentation (computing) , oxidative stress , microbiology and biotechnology , biology , dna , dna oxidation , biochemistry , programmed cell death , endocrinology , apoptosis , glutamate receptor , neuroscience , dopamine , receptor , ecology
The formation of oxidative DNA damage as a consequence of seizures remains little explored. We therefore investigated the regional and temporal profile of 8‐hydroxyl‐2′ ‐deoxyguanosine (8‐OHdG) formation, a hallmark of oxidative DNA damage and DNA fragmentation in rat brain following seizures induced by systemic kainic acid (KA). Formation of 8‐OHdG was determined via HPLC with electrochemical detection, and single‐ and double‐stranded DNA breaks were detected using in situ DNA polymerase I‐mediated biotin‐dATP nick‐translation (PANT) and terminal deoxynucleotidyl‐transferase‐mediated nick end‐labeling (TUNEL), respectively. Systemic KA (11 mg/kg) significantly increased levels of 8‐OHdG within the thalamus after 2 h, within the amygdala/piriform cortex after 4 h, and within the hippocampus after 8 h. Levels remained elevated up to sevenfold within these areas for 72 h. Smaller increases in 8‐OHdG levels were also detected within the parietal cortex and striatum. PANT‐positive cells were detected within the thalamus, amygdala/piriform cortex, and hippocampus 24‐72 h following KA injection. TUNEL‐positive cells appeared within the same brain regions and over a similar time course (24‐72 h) but were generally lower in number. The present data suggest oxidative damage to DNA may be an early consequence of epileptic seizures and a possible initiation event in the progression of seizure‐induced injury to DNA fragmentation and cell death.