Urinary ketone body loss leads to degeneration of brain white matter in elderly SLC5A8-deficient mice.

Details

Serval ID
serval:BIB_207DD46291BD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Urinary ketone body loss leads to degeneration of brain white matter in elderly SLC5A8-deficient mice.
Journal
Journal of cerebral blood flow and metabolism
Author(s)
Suissa L., Flachon V., Guigonis J.M., Olivieri C.V., Burel-Vandenbos F., Guglielmi J., Ambrosetti D., Gérard M., Franken P., Darcourt J., Pellerin L., Pourcher T., Lindenthal S.
ISSN
1559-7016 (Electronic)
ISSN-L
0271-678X
Publication state
Published
Issued date
08/2020
Peer-reviewed
Oui
Volume
40
Number
8
Pages
1709-1723
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
SLC5A8 is a sodium-coupled monocarboxylate and ketone transporter expressed in various epithelial cells. A putative role of SLC5A8 in neuroenergetics has been also hypothesized. To clarify this issue, we studied the cerebral phenotype of SLC5A8-deficient mice during aging. Elderly SLC5A8-deficient mice presented diffuse leukoencephalopathy characterized by intramyelinic oedema without demyelination suggesting chronic energetic crisis. Hypo-metabolism in the white matter of elderly SLC5A8-deficient mice was found using <sup>99m</sup> Tc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission CT (SPECT). Since the SLC5A8 protein could not be detected in the mouse brain, it was hypothesized that the leukoencephalopathy of aging SLC5A8-deficient mice was caused by the absence of slc5a8 expression in a peripheral organ, i.e. the kidney, where SLC5A8 is strongly expressed. A hyper-excretion of the ketone β-hydroxybutyrate (BHB) in the urine of SLC5A8-deficient mice was observed and showed that SLC5A8-deficient mice suffered a cerebral BHB insufficiency. Elderly SLC5A8-deficient mice also presented altered glucose metabolism. We propose that the continuous renal loss of BHB leads to a chronic energetic deficiency in the brain of elderly SLC5A8-deficient mice who are unable to counterbalance their glucose deficit. This study highlights the importance of alternative energetic substrates in neuroenergetics especially under conditions of restricted glucose availability.
Keywords
SLC5A8, brain, ketone body, kidney, white matter
Pubmed
Web of science
Create date
13/09/2019 11:29
Last modification date
28/07/2020 6:21
Usage data