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

Détails

Ressource 1Télécharger: Suissa et al_JCBFM_2019_OA.pdf (1383.24 [Ko])
Etat: Public
Version: de l'auteur⸱e
Licence: Non spécifiée
ID Serval
serval:BIB_207DD46291BD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Urinary ketone body loss leads to degeneration of brain white matter in elderly SLC5A8-deficient mice.
Périodique
Journal of cerebral blood flow and metabolism
Auteur⸱e⸱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
Statut éditorial
Publié
Date de publication
08/2020
Peer-reviewed
Oui
Volume
40
Numéro
8
Pages
1709-1723
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
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.
Mots-clé
SLC5A8, brain, ketone body, kidney, white matter
Pubmed
Web of science
Création de la notice
13/09/2019 10:29
Dernière modification de la notice
22/07/2022 6:08
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