Region-Specific Defects of Respiratory Capacities in the Ndufs4(KO) Mouse Brain

PloS One
Ernst-Bernhard KayserPhilip G Morgan

Abstract

Lack of NDUFS4, a subunit of mitochondrial complex I (NADH:ubiquinone oxidoreductase), causes Leigh syndrome (LS), a progressive encephalomyopathy. Knocking out Ndufs4, either systemically or in brain only, elicits LS in mice. In patients as well as in KO mice distinct regions of the brain degenerate while surrounding tissue survives despite systemic complex I dysfunction. For the understanding of disease etiology and ultimately for the development of rationale treatments for LS, it appears important to uncover the mechanisms that govern focal neurodegeneration. Here we used the Ndufs4(KO) mouse to investigate whether regional and temporal differences in respiratory capacity of the brain could be correlated with neurodegeneration. In the KO the respiratory capacity of synaptosomes from the degeneration prone regions olfactory bulb, brainstem and cerebellum was significantly decreased. The difference was measurable even before the onset of neurological symptoms. Furthermore, neither compensating nor exacerbating changes in glycolytic capacity of the synaptosomes were found. By contrast, the KO retained near normal levels of synaptosomal respiration in the degeneration-resistant/resilient "rest" of the brain. We also investigated...Continue Reading

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Citations

Mar 1, 2019·Scientific Reports·Chi Fung LeeRong Tian
Sep 13, 2020·Molecular Neurobiology·Hayley Christy MillerFrancois Hendrikus van der Westhuizen
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May 28, 2021·Scientific Reports·Subrata Kumar ShilYuji Owada

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Methods Mentioned

BETA
PCR
Assay
Electrophoresis

Software Mentioned

ImageJ
Allen Mouse Brain Atlas

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