Urinary ketone body loss leads to degeneration of brain white matter in elderly SLC5A8-deficient mice.
J Cereb Blood Flow Metab
; 40(8): 1709-1723, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-31506013
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 99mTc-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 ß-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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
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Transportadores de Ácidos Monocarboxílicos
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Leucoencefalopatias
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Substância Branca
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Corpos Cetônicos
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Rim
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article