Abstract |
Mutations in the nuclear encoded subunits of mitochondrial complex I ( NADH:ubiquinone oxidoreductase) may cause circumscribed cerebral lesions ranging from degeneration of the striatal and brainstem gray matter ( Leigh syndrome) to leukodystrophy. We hypothesized that such pattern of regional pathology might be due to local differences in the dependence on complex I function. Using in situ hybridization we investigated the relative expression of 33 nuclear encoded complex I subunits in different brain regions of the mouse at E11.5, E17.5, P1, P11, P28 and adult (12 weeks). With respect to timing and relative intensity of complex I gene expression we found a highly variant pattern in different regions during development. High average expression levels were detected in periods of intense neurogenesis. In cerebellar Purkinje and in hippocampal CA1/CA3 pyramidal neurons we found a second even higher peak during the period of synaptogenesis and maturation. The extraordinary dependence of these structures on complex I gene expression during synaptogenesis is in accord with our recent findings that gamma oscillations--known to be associated with higher cognitive functions of the mammalian brain--strongly depend on the complex I activity. However, with the exception of the mesencephalon, we detected only average complex I expression levels in the striatum and basal ganglia, which does not explain the exquisite vulnerability of these structures in mitochondrial disorders.
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Authors | Stefanie Wirtz, Markus Schuelke |
Journal | PloS one
(PLoS One)
Vol. 6
Issue 4
Pg. e18897
(Apr 27 2011)
ISSN: 1932-6203 [Electronic] United States |
PMID | 21556144
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Electron Transport Complex I
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Topics |
- Animals
- Brain
(embryology)
- Electron Transport Complex I
(genetics)
- Gene Expression Regulation, Enzymologic
- In Situ Hybridization
- Mice
- Mice, Inbred C57BL
- Neurogenesis
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