Krizova 2016 Abstract IOC116

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Krizova J, Macakova M, Bohuslavova B, Klima J, Ellederova Z, Zeman J, Motlik J, Hansikova H (2016) Complex I-dependent respiration decline is a marker of Huntington`s disease in spermatozoa of transgenic minipig model. Mitochondr Physiol Network 21.11

Link: Mitochondr Physiol Network 21.11

Krizova J, Macakova M, Bohuslavova B, Klima J, Ellederova Z, Zeman J, Motlik J, Hansikova H (2016)

Event: IOC116

Huntington`s disease (HD) is a fatal neurodegenerative disorder with autosomal inheritance. Patients carrying polyglutamine expansion in causal gene, huntingtin, suffer from serious cognitive and behavioral decline. Although the function of causal gene is unknown, previously a metabolic defect and a mitochondrial dysfunction were detected in several studies in HD patients and transgenic animal-models. To study the progression and therapy efficiency, detailed phenotyping even in pre-symptomatic stage of transgenic HD minipig model (TgHD), developed in Libechov, is necessary. However, no major differences in mitochondrial metabolism and respiration in skeletal muscle were observed yet. Here, we would like to present first markers of mitochondrial dysfunction in TgHD presymptomatic spermatozoa.

Spermatozoa samples were collected during three-year study, obtained repeatedly from 12 animals in three generations between 12 and 65 months of age. Mitochondrial metabolism of permeabilized spermatozoa was measured on Oroboros-O2k (respiration) and by detection of radiolabeled-substrates oxidation. The data were pair-wise statistically analyzed.

Out of 36 parameters, measured in TgHD spermatozoa, four parameters were significantly decreased: complex I-dependent respiration, oxidation of [1-14C]pyruvate and oxidation of [U-14C]malate in presence with pyruvate and malonate. None of these measurements were affected by the age of the animal. In conclusion, we observed first biochemical markers of HD in pre-sypmtomatic large-animal TgHD model. In respect of disease progression we suppose that further analyses will enable us to specify this mitochondrial defect, useful in HD etiopathogenesis elucidation.


O2k-Network Lab: CZ Prague Zeman J


Labels: MiParea: Respiration, nDNA;cell genetics, mt-Medicine  Pathology: Neurodegenerative 

Organism: Pig  Tissue;cell: Genital  Preparation: Permeabilized cells 


Pathway:HRR: Oxygraph-2k 


Affiliations

1-Lab- Study Mitochondrial Disorders, Dept Pediatrics Adolescent Med, General Univ Hospital First Fac Med, Charles Univ Prague, Czech Republic 2-Lab Cell Regeneration Plasticity, Inst Animal Physiol Genet, v.v.i., CAS, Libechov, Czech Republic. - Jana.Krizova@vfn.cz

Support

This study was supported by the Project Contract No. MSMT-28477/2014 “HUNTINGTON” 7F14308.