RS1 (Rsc1A1) deficiency limits cerebral SGLT1 expression and delays brain damage after experimental traumatic brain injury. Issue 2 (20th September 2018)

• Record Type: Journal Article
• Authors: Sebastiani, Anne; Greve, Frederik; Gölz, Christina; Förster, Carola Y.; Koepsell, Hermann; Thal, Serge C.
• Is Part Of: Journal of neurochemistry. Volume 147:Issue 2(2018)
• Page Start: 190
• Page End: 203
• Publication Date: 2018-09-20
• Subjects: controlled cortical impact -- Na+‐D‐glucose cotransporter -- RS1 -- Rsc1A1 -- SGLT1 -- traumatic brain injury; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.14551
• Languages: English
• ISSNs: 0022-3042

Abstract

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‐1β 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. Abstract : Acute cerebral lesions are associated with dysregulation of brain glucose homeostasis. Previous studies showed that RS1 protein is involved in transcriptional and post‐translational down‐regulation of the Na + ‐D‐glucose cotransporter SGLT1. We investigated whether removal of RS1 influences SGLT1 expression and outcome. One day after traumatic brain injury, SGLT1 mRNA in the ipsilateral cortex was increased 160% in wild‐type and 40% in mice lacking RS1. In RS1 KO mice lesion volume 1 day after injury was reduced and motoric disability was improved. The data provide proof of principle that targeting RS1 in brain could be beneficial for early treatment of traumatic brain injury.