Mitochondrial Dysfunction and Increased Sensitivity to Excitotoxicity in Mice Deficient in Dna Mismatch Repair.
From: Department of Biomedical Sciences and Biotechnologies, Centre of Excellence for Diagnostic and Therapeutic Innovations, University of Brescia, Brescia, Italy.
Journal of neurochemistry
- Publish Date: Jul 2006
- ISSN: 0022-3042
- Volume: 98
- Issue: 1
- Pages: 223-33
- Medium: Print
- Language: English
- Citation (JAMA): Francisconi Simona, Codenotti Mara, Ferrari Toninelli Giulia, et al. Mitochondrial Dysfunction and Increased Sensitivity to Excitotoxicity in Mice Deficient in Dna Mismatch Repair.. J. Neurochem. Jul 2006;98:223-33
Abstract
The expression profile in the hippocampus of mice lacking one allele of the MutS homologue (Msh2), gene, which is one of the most representative components of the DNA mismatch repair system, was analysed to understand whether defects in the repair or in response to DNA damage could impact significantly on brain function. The overall results suggested a reduction in mitochondrial function as indicated by gene expression analysis, biochemical and behavioural studies. In the hippocampus of Msh2+/- mice, array data, validated by RT-PCR and western blot analysis, showed reduced expression levels of genes for cytochrome c oxidase subunit 2 (CoxII), ATP synthase subunit beta and superoxide dismutase 1. Biochemically, mitochondria from the hippocampus and cortex of these mice show reduced CoxII and increased aconitase activity. Behaviourally, these alterations resulted in mice with increased vulnerability to kainic acid-induced epileptic seizures and hippocampal neuronal loss. These data suggest that lack of an efficient system involved in recognizing and repairing DNA damage may generate a brain mitochondriopathy.
Mesh Headings (Keywords): Animals, Base Pair Mismatch, Brain, Electron Transport Complex IV, Excitatory Amino Acid Agonists, Gene Expression Profiling, Kainic Acid, Mice, Mice, Knockout, Microarray Analysis, Mitochondria, MutS Homolog 2 Protein, RNA, Messenger, Reproducibility of Results, Reverse Transcriptase Polymerase Chain Reaction
Check for Full Text / PubMed Unique Identifier (PMID): 16805809
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