Differences in mitochondrial function in homogenated samples from healthy and epileptic specific brain tissues revealed by high-resolution respirometry.

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    • Source:
      Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100968751 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8278 (Electronic) Linking ISSN: 15677249 NLM ISO Abbreviation: Mitochondrion Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam ; New York : Elsevier Science, c2001-
    • Subject Terms:
    • Abstract:
      Mitochondrial dysfunction and oxidative stress are strongly implicated in neurodegenerative diseases and epilepsy. Strikingly, neurodegenerative diseases show regional specificity in vulnerability and follow distinct patterns of neuronal loss. A challenge is to understand, why mitochondria fail in particular brain regions under specific pathological conditions. A potential explanation could be provided by regional or cellular specificity of mitochondrial function. We applied high-resolution respirometry to analyze the integrated Complex I- and II (CI and CII)-linked respiration, the activity of Complex IV, and the combined CI&II-linked oxidative phosphorylation (OXPHOS)- and electron-transfer system (ETS)-capacity in microsamples obtained from distinct regions of the mouse brain. We compared different approaches to assess mitochondrial density and suggest flux control ratios as a valid method to normalize respiration to mitochondrial density. This approach revealed significant differences of CI- and CII-linked OXPHOS capacity and coupling control between motor cortex, striatum, hippocampus and pons of naïve mice. CI-linked respiration was highest in motor cortex, while CII-linked respiration predominated in the striatum. To investigate if this method could also determine differences in normal and disease states within the same brain region, we compared hippocampal homogenates in a chronic epilepsy model. Three weeks after stereotaxic injection of kainate, there was a down-regulation of CI- and upregulation of CII-linked respiration in the resulting epileptic ipsilateral hippocampus compared to the contralateral one. In summary, respirometric OXPHOS analysis provides a very sensitive diagnostic approach using small amounts of distinct brain tissues. In a single assay, information is obtained on numerous OXPHOS parameters as indicators of tissue-specific mitochondrial performance.
    • Grant Information:
      I 977 Austria FWF_ Austrian Science Fund FWF; W 1206 Austria FWF_ Austrian Science Fund FWF
    • Contributed Indexing:
      Keywords: Brain regions; Epilepsy; Mitochondria; Neurodegeneration; Respirometry
    • Publication Date:
      Date Created: 20151031 Date Completed: 20160825 Latest Revision: 20210109
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.mito.2015.10.007
    • Accession Number:
      26516105