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Sex-associated differences in mitochondrial function in human peripheral blood mononuclear cells (PBMCs) and brain.


ABSTRACT:

Background

Alzheimer's disease (AD) is the most common form of dementia, and it affects more women than men. Mitochondrial dysfunction (MD) plays a key role in AD, and it is detectable at an early stage of the degenerative process in peripheral tissues, such as peripheral mononuclear blood cells (PBMCs). However, whether these changes are also reflected in cerebral energy metabolism and whether sex-specific differences in mitochondrial function occur are not clear. Therefore, we estimated the correlation between mitochondrial function in PBMCs and brain energy metabolites and examined sex-specific differences in healthy participants to elucidate these issues.

Methods

The current pilot study included 9 male and 15 female healthy adults (mean age 30.8?±?7.1 years). Respiration and activity of mitochondrial respiratory complexes were measured using a Clarke-electrode (Oxygraph-2k system), and adenosine triphosphate (ATP) levels were determined using a bioluminescence-based assay in isolated PBMCs. Citrate synthase activity as a mitochondrial marker was measured using a photometric assay. Concentrations of brain energy metabolites were quantified in the same individuals using 1H-magnetic resonance spectroscopy (MRS).

Results

We detected sex-associated differences in mitochondrial function. Mitochondrial complexes I, I+II, and IV and uncoupled respiration and electron transport system (ETS) capacity in PBMCs isolated from blood samples of females were significantly (p??50%) of gray matter (GM) (p?ConclusionsOur study revealed sex-associated differences in mitochondrial function in healthy participants. The underlying mechanisms must be elucidated in more detail, but our study suggests that mitochondrial function in PBMCs is a feasible surrogate marker to detect differences in mitochondrial function and energy metabolism in humans and it underscores the necessity of sex-specific approaches in therapies that target mitochondrial dysfunction.

SUBMITTER: Silaidos C 

PROVIDER: S-EPMC6060503 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Sex-associated differences in mitochondrial function in human peripheral blood mononuclear cells (PBMCs) and brain.

Silaidos C C   Pilatus U U   Grewal R R   Matura S S   Lienerth B B   Pantel J J   Eckert G P GP  

Biology of sex differences 20180725 1


<h4>Background</h4>Alzheimer's disease (AD) is the most common form of dementia, and it affects more women than men. Mitochondrial dysfunction (MD) plays a key role in AD, and it is detectable at an early stage of the degenerative process in peripheral tissues, such as peripheral mononuclear blood cells (PBMCs). However, whether these changes are also reflected in cerebral energy metabolism and whether sex-specific differences in mitochondrial function occur are not clear. Therefore, we estimate  ...[more]

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