Sodium/glucose cotransporter 2 is expressed in choroid plexus epithelial cells and ependymal cells in human and mouse brains.
SLC5A2
central nervous system
diabetes mellitus
immunolabeling
mRNA
Journal
Neuropathology : official journal of the Japanese Society of Neuropathology
ISSN: 1440-1789
Titre abrégé: Neuropathology
Pays: Australia
ID NLM: 9606526
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
16
01
2020
revised:
30
03
2020
accepted:
10
04
2020
pubmed:
4
6
2020
medline:
15
10
2021
entrez:
4
6
2020
Statut:
ppublish
Résumé
Diabetes mellitus (DM) is now recognized as one of the risk factors for Alzheimer's disease (AD), and the disease-modifying effects of anti-diabetic drugs on AD have recently been attracting great attention. Sodium/glucose cotransporter 2 (SGLT2) inhibitors are a new class of anti-diabetic drugs targeting the SGLT2/solute carrier family 5 member 2 (SLC5A2) protein, which is known to localize exclusively in the brush border membrane of early proximal tubules in the kidney. However, recent data suggest that it is also expressed in other tissues. In the present study, we investigated the expression of SGLT2/SLC5A2 in human and mouse brains. Immunohistochemical staining of paraffin sections from autopsied human brains and C3H/He mouse brains revealed granular cytoplasmic immunoreactivity in choroid plexus epithelial cells and ependymal cells. Immunoblot analysis of the membrane fraction of mouse choroid plexus showed distinct immunoreactive bands at 70 and 26 kDa. Band patterns around 70 kDa in the membrane fraction of the choroid plexus were different from those in the kidney. Reverse transcription-polymerase chain reaction analysis confirmed the expression of Slc5a2 mRNA in the mouse choroid plexus. Our results provide in vivo evidence that SGLT2/SLC5A2 is expressed in cells facing the cerebrospinal fluid, in addition to early proximal tubular epithelial cells. These findings suggest that SGLT2 inhibitors may have another site of action in the brain. The effects of SGLT2 inhibitors on brain function and AD progression merit further investigation to develop better treatment options for DM patients.
Identifiants
pubmed: 32488949
doi: 10.1111/neup.12665
pmc: PMC7587001
doi:
Substances chimiques
SLC5A2 protein, human
0
Slc5a2 protein, mouse
0
Sodium-Glucose Transporter 2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
482-491Subventions
Organisme : Japan Society for the Promotion of Science
ID : 17K08788
Organisme : Japan Society for the Promotion of Science
ID : 19K07508
Informations de copyright
© 2020 The Authors. Neuropathology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Neuropathology.
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