Burtscher J 2016 Abstract MitoFit Science Camp 2016
|Oxidative phosphorylation in the healthy and epileptic mouse brain.|
Mitochondrial dysfunction appears to be a common factor in neurodegenerative diseases. Strikingly, neurodegenerative diseases show regional specificity in vulnerability and follow distinct patterns of neuronal loss. A challenge is to understand, how mitochondrial failure in particular brain regions contributes to specific pathological conditions .
High-resolution respirometry revealed significant differences of Complex I- and II- (CI and CII) linked oxidative phosphorylation (OXPHOS) capacity and coupling control between motor cortex, striatum, hippocampus and pons of naïve mice. CI-linked respiration was highest in motor cortex. In contrast, CII-linked capacity was especially important in the striatum. Apparent excess capacities of the electron transfer-pathway (ET-pathway) over OXPHOS also differed between regions. These differences may indicate risk factors for region-specific neuronal vulnerabilities.
In the kainic acid (KA) model of temporal lobe epilepsy in mice, we observed markedly decreased absolute CI- and CII- linked oxygen consumption and also decreased ET-capacity in the injected dorsal hippocampus 2 days after KA. When normalized to ET-capacity, CII-linked respiration was significantly increased compared to controls. 3 weeks after KA-injection, tissue-mass specific CII-linked oxygen consumption reached control levels, but was elevated when normalized to ET-capacity. Tissue-mass specific CI-linked oxygen consumption and ET-capacity remained decreased.
In summary, respirometric OXPHOS analysis allows detailed analysis of mitochondrial function from small amounts of specific brain regions (about 2 mg). It thus enables comparison of different brain tissues implicated in neurodegenerative diseases of the healthy mouse and disease models, while leaving enough material for further studies on the tissues.
Labels: MiParea: Respiration Pathology: Neurodegenerative
Organism: Mouse Tissue;cell: Nervous system Preparation: Homogenate
Coupling state: OXPHOS, ET Pathway: N, S HRR: Oxygraph-2k Event: B2 MitoFit Science Camp 2016
Affiliations and Support
1-Dept Pharmacol, Med Univ Innsbruck; 2-D. Swarowski Research Lab, Dept Visceral, Transplant Thoracic Surgery, Med Univ Innsbruck; 3-Oroboros Instruments, Innsbruck; Austria. - [email protected]
Supported by the Austrian Science Fund (FWF), project W1206-B05
- Burtscher J, Zangrandi L, Schwarzer C, Gnaiger E (2015) Differences in mitochondrial function in homogenated samples from healthy and epileptic specific brain tissues revealed by high-resolution respirometry. Mitochondrion 25:104-12.