RGD Reference Report - Mitochondrial DNA damage and impaired base excision repair during epileptogenesis. - Rat Genome Database

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Mitochondrial DNA damage and impaired base excision repair during epileptogenesis.

Authors: Jarrett, SG  Liang, LP  Hellier, JL  Staley, KJ  Patel, M 
Citation: Jarrett SG, etal., Neurobiol Dis. 2008 Apr;30(1):130-8. Epub 2008 Jan 5.
RGD ID: 2317139
Pubmed: PMID:18295498   (View Abstract at PubMed)
PMCID: PMC2696045   (View Article at PubMed Central)
DOI: DOI:10.1016/j.nbd.2007.12.009   (Journal Full-text)

Oxidative stress and mitochondrial dysfunction are acute consequences of status epilepticus (SE). However, the role of mitochondrial oxidative stress and genomic instability during epileptogenesis remains unknown. Using the kainate animal model of temporal lobe epilepsy, we investigated oxidative mitochondrial DNA (mtDNA) damage and changes in the mitochondrial base excision repair pathway (mtBER) in the rat hippocampus for a period of 3 months after SE. Acute seizure activity caused a time-dependent increase in mitochondrial, but not nuclear 8-hydroxy-2-deoxyguanosine (8-OHdG/2dG) levels and a greater frequency of mtDNA lesions. This was accompanied by increased mitochondrial H2O2 production and a transient decrease in mtDNA repair capacity. The mtBER proteins 8-oxoguanine glycosylase (Ogg1) and DNA polymerase gamma (Pol gamma) demonstrated elevated expression at mRNA and protein levels shortly after SE and this was followed by a gradual improvement in mtDNA repair capacity. Recurrent seizures associated with the chronic phase of epilepsy coincided with the accumulation of mtDNA damage, increased mitochondrial H2O2 levels, decreased expression of Ogg1 and Pol gamma and impaired mtDNA repair capacity. Together, increased oxidative mtDNA damage, mitochondrial H2O2 production and alterations in the mtBER pathway provide evidence for mitochondrial oxidative stress in epilepsy and suggest that mitochondrial injury may contribute to epileptogenesis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  

Objects Annotated

Genes (Rattus norvegicus)
Ogg1  (8-oxoguanine DNA glycosylase)
Polg  (DNA polymerase gamma, catalytic subunit)

Genes (Mus musculus)
Ogg1  (8-oxoguanine DNA-glycosylase 1)
Polg  (polymerase (DNA directed), gamma)

Genes (Homo sapiens)
OGG1  (8-oxoguanine DNA glycosylase)
POLG  (DNA polymerase gamma, catalytic subunit)


Additional Information