Persistent impairment of mitochondrial and tissue redox status during lithium-pilocarpine-induced epileptogenesis.

Abstract

Mitochondrial dysfunction and oxidative stress are known to occur following acute seizure activity but their contribution during epileptogenesis is largely unknown. The goal of this study was to determine the extent of mitochondrial oxidative stress, changes to redox status, and mitochondrial DNA (mtDNA) damage during epileptogenesis in the lithium-pilocarpine model of temporal lobe epilepsy. Mitochondrial oxidative stress, changes in tissue and mitochondrial redox status, and mtDNA damage were assessed in the hippocampus and neocortex of Sprague-Dawley rats at time points (24h to 3months) following lithium-pilocarpine administration. A time-dependent increase in mitochondrial hydrogen peroxide (H(2)O(2)) production coincident with increased mtDNA lesion frequency in the hippocampus was observed during epileptogenesis. Acute increases (24-48h) in H(2)O(2) production and mtDNA lesion frequency were dependent on the severity of convulsive seizure activity during initial status epilepticus. Tissue levels of GSH, GSH/GSSG, coenzyme A (CoASH), and CoASH/CoASSG were persistently impaired at all measured time points throughout epileptogenesis, that is, acutely (24-48h), during the 'latent period' (48h to 7days), and chronic epilepsy (21days to 3months). Together with our previous work, these results demonstrate the model independence of mitochondrial oxidative stress, genomic instability, and persistent impairment of mitochondrial specific redox status during epileptogenesis. Lasting impairment of mitochondrial and tissue redox status during the latent period, in addition to the acute and chronic phases of epileptogenesis, suggests that redox-dependent processes may contribute to the progression of epileptogenesis in experimental temporal lobe epilepsy.

• Authors: Simon Waldbaum, Li-Ping Liang, Manisha Patel
• Journal: Journal of neurochemistry (J Neurochem) Vol. 115 Issue 5 Pg. 1172-82 (Dec 2010) ISSN: 1471-4159 [Electronic] England
• PMID: 21219330 (Publication Type: Journal Article)
• Copyright: © 2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry.

Chemical References

• DNA, Mitochondrial
• Pilocarpine
• Lithium

Topics

• Animals
• Brain (drug effects, metabolism, physiopathology)
• Brain Chemistry (drug effects, physiology)
• DNA, Mitochondrial (drug effects, physiology)
• Disease Models, Animal
• Energy Metabolism (drug effects, physiology)
• Epilepsy, Temporal Lobe (chemically induced, metabolism, physiopathology)
• Genomic Instability (drug effects, physiology)
• Lithium (pharmacology)
• Male
• Mitochondria (drug effects, metabolism)
• Oxidation-Reduction (drug effects)
• Oxidative Stress (drug effects, physiology)
• Pilocarpine (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Time