Mizagliflozin, a selective SGLT1 inhibitor, improves vascular cognitive impairment in a mouse model of small vessel disease

Abstract Previously, we showed that sodium/glucose cotransporter 1 (SGLT1) participates in vascular cognitive impairment in small vessel disease. We hypothesized that SGLT1 inhibitors can improve the small vessel disease induced‐vascular cognitive impairment. We examined the effects of mizagliflozin...

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Autores principales:	Nanae Ishida, Maki Saito, Sachiko Sato, Yu Tezuka, Atsushi Sanbe, Eiichi Taira, Masamichi Hirose
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	cerebral small vessel disease mizagliflozin SGLT1 vascular cognitive impairment Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/1e0e990177ba4dcf88705313dbc2b738
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spelling	oai:doaj.org-article:1e0e990177ba4dcf88705313dbc2b7382021-11-16T13:45:55ZMizagliflozin, a selective SGLT1 inhibitor, improves vascular cognitive impairment in a mouse model of small vessel disease2052-170710.1002/prp2.869https://doaj.org/article/1e0e990177ba4dcf88705313dbc2b7382021-10-01T00:00:00Zhttps://doi.org/10.1002/prp2.869https://doaj.org/toc/2052-1707Abstract Previously, we showed that sodium/glucose cotransporter 1 (SGLT1) participates in vascular cognitive impairment in small vessel disease. We hypothesized that SGLT1 inhibitors can improve the small vessel disease induced‐vascular cognitive impairment. We examined the effects of mizagliflozin, a selective SGLT1 inhibitor, and phlorizin, a non‐selective SGLT inhibitor, on vascular cognitive impairment in a mouse model of small vessel disease. Small vessel disease was created using a mouse model of asymmetric common carotid artery surgery (ACAS). Two and/or 4 weeks after ACAS, all experiments were performed. Cerebral blood flow (CBF) was decreased in ACAS compared with sham‐operated mice. Phlorizin but not mizagliflozin reversed the decreased CBF of ACAS mice. Both mizagliflozin and phlorizin reversed the ACAS‐induced decrease in the latency to fall in a wire hang test of ACAS mice. Moreover, they reversed the ACAS‐induced longer escape latencies in the Morris water maze test of ACAS mice. ACAS increased SGLT1 and proinflammatory cytokine gene expressions in mouse brains and phlorizin but not mizagliflozin normalized all gene expressions in ACAS mice. Hematoxylin/eosin staining demonstrated that they inhibited pyknotic cell death in the ACAS mouse hippocampus. In PC12HS cells, IL‐1β increased SGLT1 expression and decreased survival rates of cells. Both mizagliflozin and phlorizin increased the survival rates of IL‐1β‐treated PC12HS cells. These results suggest that mizagliflozin and phlorizin can improve vascular cognitive impairment through the inhibition of neural SGLT1 and phlorizin also does so through the improvement of CBF in a mouse model of small vessel disease.Nanae IshidaMaki SaitoSachiko SatoYu TezukaAtsushi SanbeEiichi TairaMasamichi HiroseWileyarticlecerebral small vessel diseasemizagliflozinSGLT1vascular cognitive impairmentTherapeutics. PharmacologyRM1-950ENPharmacology Research & Perspectives, Vol 9, Iss 5, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cerebral small vessel disease mizagliflozin SGLT1 vascular cognitive impairment Therapeutics. Pharmacology RM1-950
spellingShingle	cerebral small vessel disease mizagliflozin SGLT1 vascular cognitive impairment Therapeutics. Pharmacology RM1-950 Nanae Ishida Maki Saito Sachiko Sato Yu Tezuka Atsushi Sanbe Eiichi Taira Masamichi Hirose Mizagliflozin, a selective SGLT1 inhibitor, improves vascular cognitive impairment in a mouse model of small vessel disease
description	Abstract Previously, we showed that sodium/glucose cotransporter 1 (SGLT1) participates in vascular cognitive impairment in small vessel disease. We hypothesized that SGLT1 inhibitors can improve the small vessel disease induced‐vascular cognitive impairment. We examined the effects of mizagliflozin, a selective SGLT1 inhibitor, and phlorizin, a non‐selective SGLT inhibitor, on vascular cognitive impairment in a mouse model of small vessel disease. Small vessel disease was created using a mouse model of asymmetric common carotid artery surgery (ACAS). Two and/or 4 weeks after ACAS, all experiments were performed. Cerebral blood flow (CBF) was decreased in ACAS compared with sham‐operated mice. Phlorizin but not mizagliflozin reversed the decreased CBF of ACAS mice. Both mizagliflozin and phlorizin reversed the ACAS‐induced decrease in the latency to fall in a wire hang test of ACAS mice. Moreover, they reversed the ACAS‐induced longer escape latencies in the Morris water maze test of ACAS mice. ACAS increased SGLT1 and proinflammatory cytokine gene expressions in mouse brains and phlorizin but not mizagliflozin normalized all gene expressions in ACAS mice. Hematoxylin/eosin staining demonstrated that they inhibited pyknotic cell death in the ACAS mouse hippocampus. In PC12HS cells, IL‐1β increased SGLT1 expression and decreased survival rates of cells. Both mizagliflozin and phlorizin increased the survival rates of IL‐1β‐treated PC12HS cells. These results suggest that mizagliflozin and phlorizin can improve vascular cognitive impairment through the inhibition of neural SGLT1 and phlorizin also does so through the improvement of CBF in a mouse model of small vessel disease.
format	article
author	Nanae Ishida Maki Saito Sachiko Sato Yu Tezuka Atsushi Sanbe Eiichi Taira Masamichi Hirose
author_facet	Nanae Ishida Maki Saito Sachiko Sato Yu Tezuka Atsushi Sanbe Eiichi Taira Masamichi Hirose
author_sort	Nanae Ishida
title	Mizagliflozin, a selective SGLT1 inhibitor, improves vascular cognitive impairment in a mouse model of small vessel disease
title_short	Mizagliflozin, a selective SGLT1 inhibitor, improves vascular cognitive impairment in a mouse model of small vessel disease
title_full	Mizagliflozin, a selective SGLT1 inhibitor, improves vascular cognitive impairment in a mouse model of small vessel disease
title_fullStr	Mizagliflozin, a selective SGLT1 inhibitor, improves vascular cognitive impairment in a mouse model of small vessel disease
title_full_unstemmed	Mizagliflozin, a selective SGLT1 inhibitor, improves vascular cognitive impairment in a mouse model of small vessel disease
title_sort	mizagliflozin, a selective sglt1 inhibitor, improves vascular cognitive impairment in a mouse model of small vessel disease
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/1e0e990177ba4dcf88705313dbc2b738
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Mizagliflozin, a selective SGLT1 inhibitor, improves vascular cognitive impairment in a mouse model of small vessel disease

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