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Distinct age and differentiation-state dependent metabolic profiles of oligodendrocytes under optimal and stress conditions.

ABSTRACT: Within the microenvironment of multiple sclerosis lesions, oligodendrocytes are subject to metabolic stress reflecting effects of focal ischemia and inflammation. Previous studies have shown that under optimal conditions in vitro, the respiratory activity of human adult brain-derived oligodendrocytes is lower and more predominantly glycolytic compared to oligodendrocytes differentiated in vitro from post natal rat brain oligodendrocyte progenitor cells. In response to sub-lethal metabolic stress, adult human oligodendrocytes reduce overall energy production rate impacting the capacity to maintain myelination. Here, we directly compare the metabolic profiles of oligodendrocytes derived from adult rat brain with oligodendrocytes newly differentiated in vitro from oligodendrocyte progenitor cells obtained from the post natal rat brain, under both optimal culture and metabolic stress (low/no glucose) conditions. Oxygen consumption and extracellular acidification rates were measured using a Seahorse extracellular flux analyzer. Our findings indicate that under optimal conditions, adult rat oligodendrocytes preferentially use glycolysis whereas newly differentiated post natal rat oligodendrocytes, and the oligodendrocyte progenitor cells from which they are derived, mainly utilize oxidative phosphorylation to produce ATP. Metabolic stress increases the rate of ATP production via oxidative phosphorylation and significantly reduces glycolysis in adult oligodendrocytes. The rate of ATP production was relatively unchanged in newly differentiated post natal oligodendrocytes under these stress conditions, while it was significantly reduced in oligodendrocyte progenitor cells. Our study indicates that both age and maturation influence the metabolic profile under optimal and stressed conditions, emphasizing the need to consider these variables for in vitro studies that aim to model adult human disease.

SUBMITTER: Rao VTS

PROVIDER: S-EPMC5549710 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Distinct age and differentiation-state dependent metabolic profiles of oligodendrocytes under optimal and stress conditions.

Rao Vijayaraghava T S VTS Khan Damla D Cui Qiao-Ling QL Fuh Shih-Chieh SC Hossain Shireen S Almazan Guillermina G Multhaup Gerhard G Healy Luke M LM Kennedy Timothy E TE Antel Jack P JP

PloS one 20170808 8

Within the microenvironment of multiple sclerosis lesions, oligodendrocytes are subject to metabolic stress reflecting effects of focal ischemia and inflammation. Previous studies have shown that under optimal conditions in vitro, the respiratory activity of human adult brain-derived oligodendrocytes is lower and more predominantly glycolytic compared to oligodendrocytes differentiated in vitro from post natal rat brain oligodendrocyte progenitor cells. In response to sub-lethal metabolic stress ...[more]

PMID: 28792512

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Project description:There is much research about those who exit the labour market prematurely, however, comparatively little is known about people working longer and about their employment and working conditions. In this paper, we describe the employment and working conditions of men and women working between 65 and 80 years, and compare them with previous conditions of those retired in the same age group. Analyses are based on wave 4 data from the Survey of Health, Ageing and Retirement in Europe (SHARE) with information collected between 2009 and 2011 from 17,625 older men and women across 16 European countries. Besides socio-demographic and health-related factors (physical and mental health), the focus lies on employment conditions (e.g. employment status, occupational position and working hours) and on stressful working conditions, measured in terms of low control at work and effort-reward imbalance. In case of retired people, information on working conditions refer to the last job before retirement. Following descriptive analyses, we then conduct multivariable analyses and investigate how working conditions and poor health are related to labour market participation (i.e. random intercept models accounting for country affiliation and adjusted for potential confounders). Results illustrate that people working between the ages of 65 and 80 are more likely to be self-employed (either with or without employees) and work in advantaged occupational positions. Furthermore, findings reveal that psychosocial working conditions are generally better than the conditions retired respondents had in their last job. Finally, in contrast to those who work, health tends to be worse among retired people. In conclusion, findings deliver empirical evidence that paid employment beyond age 65 is more common among self-employed workers throughout Europe, in advantaged occupations and under-favourable psychosocial circumstances, and that this group of workers are in considerably good mental and physical health. This highlights that policies aimed at increasing the state pension age beyond the age of 65 years put pressure on specific disadvantaged groups of men and women.

Dataset Information

Distinct age and differentiation-state dependent metabolic profiles of oligodendrocytes under optimal and stress conditions.

Publications

Distinct age and differentiation-state dependent metabolic profiles of oligodendrocytes under optimal and stress conditions.

Similar Datasets

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