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Tytuł:
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RS1 (Rsc1A1) deficiency limits cerebral SGLT1 expression and delays brain damage after experimental traumatic brain injury.
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Autorzy:
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Sebastiani A; Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Greve F; Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Gölz C; Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Förster CY; Department of Anesthesiology, University of Würzburg, Würzburg, Germany.
Koepsell H; Institute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
Thal SC; Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
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Źródło:
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Journal of neurochemistry [J Neurochem] 2018 Oct; Vol. 147 (2), pp. 190-203. Date of Electronic Publication: 2018 Sep 20.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: 2001- : Oxford, UK : Wiley on behalf of the International Society for Neurochemistry
Original Publication: New York : Raven Press
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MeSH Terms:
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Brain/*pathology
Brain Injuries, Traumatic/*metabolism
Brain Injuries, Traumatic/*pathology
Cell Adhesion Molecules/*deficiency
Sodium-Glucose Transporter 1/*biosynthesis
Animals ; Brain Chemistry/genetics ; Brain Edema/pathology ; Brain Edema/prevention & control ; Cell Adhesion Molecules/genetics ; Cerebral Cortex/drug effects ; Cerebral Cortex/metabolism ; Cytokines/metabolism ; Eye Proteins/genetics ; Gene Expression/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microglia/metabolism ; Movement Disorders/etiology ; Movement Disorders/prevention & control ; Up-Regulation
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Contributed Indexing:
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Keywords: Na+-D-glucose cotransporter; RS1; Rsc1A1; SGLT1; controlled cortical impact; traumatic brain injury
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Molecular Sequence:
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GENBANK NM_008907; NM_019810; NM_023544; NM_011400; NM_008361; NM_031168
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Substance Nomenclature:
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0 (Cell Adhesion Molecules)
0 (Cytokines)
0 (Eye Proteins)
0 (RS1 protein, mouse)
0 (Slc5a1 protein, mouse)
0 (Sodium-Glucose Transporter 1)
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Entry Date(s):
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Date Created: 20180720 Date Completed: 20191002 Latest Revision: 20191210
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Update Code:
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20240105
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DOI:
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10.1111/jnc.14551
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PMID:
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30022488
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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.
(© 2018 International Society for Neurochemistry.)
