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Differential expression of glucose-metabolizing enzymes in multiple sclerosis lesions

Overview of attention for article published in Acta Neuropathologica Communications, December 2015
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Title
Differential expression of glucose-metabolizing enzymes in multiple sclerosis lesions
Published in
Acta Neuropathologica Communications, December 2015
DOI 10.1186/s40478-015-0261-8
Pubmed ID
Authors

Philip G. Nijland, Remco J. Molenaar, Susanne M. A. van der Pol, Paul van der Valk, Cornelis J. F. van Noorden, Helga E. de Vries, Jack van Horssen

Abstract

Demyelinated axons in multiple sclerosis (MS) lesions have an increased energy demand in order to maintain conduction. However, oxidative stress-induced mitochondrial dysfunction likely alters glucose metabolism and consequently impairs neuronal function in MS. Imaging and pathological studies indicate that glucose metabolism is altered in MS, although the underlying mechanisms and its role in neurodegeneration remain elusive. We investigated expression patterns of key enzymes involved in glycolysis, tricarboxylic acid (TCA) cycle and lactate metabolism in well-characterized MS tissue to establish which regulators of glucose metabolism are involved in MS and to identify underlying mechanisms. Expression levels of glycolytic enzymes were increased in active and inactive MS lesions, whereas expression levels of enzymes involved in the TCA cycle were upregulated in active MS lesions, but not in inactive MS lesions. We observed reduced expression and production capacity of mitochondrial α-ketoglutarate dehydrogenase (αKGDH) in demyelinated axons, which correlated with signs of axonal dysfunction. In inactive lesions, increased expression of lactate-producing enzymes was observed in astrocytes, whereas lactate-catabolising enzymes were mainly detected in axons. Our results demonstrate that the expression of various enzymes involved in glucose metabolism is increased in both astrocytes and axons in active MS lesions. In inactive MS lesions, we provide evidence that astrocytes undergo a glycolytic shift resulting in enhanced astrocyte-axon lactate shuttling, which may be pivotal for the survival of demyelinated axons. In conclusion, we show that key enzymes involved in energy metabolism are differentially expressed in active and inactive MS lesions. Our findings imply that, in addition to reduced oxidative phosphorylation activity, other bioenergetic pathways are affected as well, which may contribute to ongoing axonal degeneration in MS.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 44 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 9 20%
Researcher 7 16%
Student > Ph. D. Student 6 14%
Professor 3 7%
Librarian 2 5%
Other 7 16%
Unknown 10 23%
Readers by discipline Count As %
Neuroscience 10 23%
Biochemistry, Genetics and Molecular Biology 10 23%
Medicine and Dentistry 7 16%
Agricultural and Biological Sciences 2 5%
Computer Science 1 2%
Other 6 14%
Unknown 8 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 December 2015.
All research outputs
#3,307,860
of 6,818,838 outputs
Outputs from Acta Neuropathologica Communications
#218
of 328 outputs
Outputs of similar age
#143,807
of 283,414 outputs
Outputs of similar age from Acta Neuropathologica Communications
#23
of 27 outputs
Altmetric has tracked 6,818,838 research outputs across all sources so far. This one is in the 29th percentile – i.e., 29% of other outputs scored the same or lower than it.
So far Altmetric has tracked 328 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one is in the 25th percentile – i.e., 25% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 283,414 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 27 others from the same source and published within six weeks on either side of this one. This one is in the 7th percentile – i.e., 7% of its contemporaries scored the same or lower than it.