Urinary ketone body loss leads to degeneration of brain white matter in elderly SLC5A8-deficient mice.
Fiche du document
- doi: 10.1177/0271678X19873662
- issn: 0271-678X
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1177/0271678X19873662
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/31506013
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1559-7016
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_207DD46291BD8
info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer
Sujets proches
Mouse House mice Mus musculus House mouseCiter ce document
L. Suissa et al., « Urinary ketone body loss leads to degeneration of brain white matter in elderly SLC5A8-deficient mice. », Serveur académique Lausannois, ID : 10.1177/0271678X19873662
Métriques
Partage / Export
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 99m 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.