RS1 (Rsc1A1) deficiency limits cerebral SGLT1 expression and delays brain damage after experimental traumatic brain injury.
J Neurochem
; 147(2): 190-203, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-30022488
ABSTRACT
Acute cerebral lesions are associated with dysregulation of brain glucose homeostasis. Previous studies showed that knockdown of Na+ -D-glucose cotransporter SGLT1 impaired outcome after middle cerebral artery occlusion and that widely expressed intracellular RS1 (RSC1A1) is involved in transcriptional and post-translational down-regulation of SGLT1. In the present study, we investigated whether SGLT1 is up-regulated during traumatic brain injury (TBI) and whether removal of RS1 in mice (RS1-KO) influences SGLT1 expression and outcome. Unexpectedly, brain SGLT1 mRNA in RS1-KO was similar to wild-type whereas it was increased in small intestine and decreased in kidney. One day after TBI, SGLT1 mRNA in the ipsilateral cortex was increased 160% in wild-type and 40% in RS1-KO. After RS1 removal lesion volume 1 day after TBI was reduced by 12%, brain edema was reduced by 28%, and motoric disability determined by a beam walking test was improved. In contrast, RS1 removal did neither influence glucose and glycogen accumulation 1 day after TBI nor up-regulation of inflammatory cytokines TNF-α, IL-1ß and IL-6 or microglia activation 1 or 5 days after TBI. The data provide proof of principle that inhibition or down-regulation of SGLT1 by targeting RS1 in brain could be beneficial for early treatment of TBI.
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Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Moléculas de Adesão Celular
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Transportador 1 de Glucose-Sódio
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Lesões Encefálicas Traumáticas
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha