Mitochondrial Metabolism in a Large-Animal Model of Huntington Disease: The Hunt for Biomarkers in the Spermatozoa of Presymptomatic Minipigs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F17%3A10364256" target="_blank" >RIV/00064165:_____/17:10364256 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985904:_____/17:00486661 RIV/00216208:11110/17:10364256

Výsledek na webu

<a href="http://dx.doi.org/10.1159/000475467" target="_blank" >http://dx.doi.org/10.1159/000475467</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1159/000475467" target="_blank" >10.1159/000475467</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Mitochondrial Metabolism in a Large-Animal Model of Huntington Disease: The Hunt for Biomarkers in the Spermatozoa of Presymptomatic Minipigs

Popis výsledku v původním jazyce

Background: Huntington disease (HD) is a fatal neurode-generative disorder involving reduced muscle coordination, mental and behavioral changes, and testicular degeneration. In order to further clarify the decreased fertility and penetration ability of the spermatozoa of transgenic HD minipig boars (TgHD), we applied a set of mitochondrial metabolism (MM) parameter measurements to this promising biological material, which can be collected noninvasively in longitudinal studies. Objective: We aimed to optimize methods for MM measurements in spermatozoa and to establish possible biomarkers of HD in TgHD spermatozoa expressing the N-terminal part of mutated human huntingtin. Methods: Semen samples from 12 TgHD and wild-type animals, aged 12-65 months, were obtained repeatedly during the study. Respiration was measured by polarography, MM was assessed by the detection of oxidation of radiolabeled substrates (mitochondrial energy-generating system; MEGS), and the content of the oxidative phosphorylation system subunits was detected by Western blot. Three possibly interfering factors were statistically analyzed: the effect of HD, generation and aging. Results: We found 5 MM parameters which were significantly diminished in TgHD spermatozoa and propose 3 specific MEGS incubations and complex I-dependent respiration as potential biomarkers of HD in TgHD spermatozoa. Conclusions: Our results suggest a link between the gain of toxic function of mutated huntingtin in TgHD spermatozoa and the observed MM and/or glycolytic impairment. We determined 4 biomarkers useful for HD phenotyping and experimental therapy monitoring studies in TgHD minipigs. (C) 2017 S. Karger AG, Basel

Název v anglickém jazyce

Mitochondrial Metabolism in a Large-Animal Model of Huntington Disease: The Hunt for Biomarkers in the Spermatozoa of Presymptomatic Minipigs

Popis výsledku anglicky

Background: Huntington disease (HD) is a fatal neurode-generative disorder involving reduced muscle coordination, mental and behavioral changes, and testicular degeneration. In order to further clarify the decreased fertility and penetration ability of the spermatozoa of transgenic HD minipig boars (TgHD), we applied a set of mitochondrial metabolism (MM) parameter measurements to this promising biological material, which can be collected noninvasively in longitudinal studies. Objective: We aimed to optimize methods for MM measurements in spermatozoa and to establish possible biomarkers of HD in TgHD spermatozoa expressing the N-terminal part of mutated human huntingtin. Methods: Semen samples from 12 TgHD and wild-type animals, aged 12-65 months, were obtained repeatedly during the study. Respiration was measured by polarography, MM was assessed by the detection of oxidation of radiolabeled substrates (mitochondrial energy-generating system; MEGS), and the content of the oxidative phosphorylation system subunits was detected by Western blot. Three possibly interfering factors were statistically analyzed: the effect of HD, generation and aging. Results: We found 5 MM parameters which were significantly diminished in TgHD spermatozoa and propose 3 specific MEGS incubations and complex I-dependent respiration as potential biomarkers of HD in TgHD spermatozoa. Conclusions: Our results suggest a link between the gain of toxic function of mutated huntingtin in TgHD spermatozoa and the observed MM and/or glycolytic impairment. We determined 4 biomarkers useful for HD phenotyping and experimental therapy monitoring studies in TgHD minipigs. (C) 2017 S. Karger AG, Basel

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10600 - Biological sciences

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Neurodegenerative Diseases

ISSN

1660-2854

e-ISSN

—

Svazek periodika

17

Číslo periodika v rámci svazku

4-5

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

14

Strana od-do

213-226

Kód UT WoS článku

000407170000011

EID výsledku v databázi Scopus

2-s2.0-85021161675