慢性的脳虚血誘発認知障害に対するmizagliflozinの効果

• Published in: 日本薬理学会年会要旨集 p. 3-P-195
• Main Authors: 弘瀬, 雅教, 佐藤, 幸子, 手塚, 優, 平, 英一, 斉藤, 麻希, 三部, 篤, 石田, 菜々絵
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: ischemia; memory; neuronal death; transporter
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.95.0_3-P-195

Introduction: Sodium/glucose cotransporter 1 (SGLT1) participates in ischemia-reperfusion-induced neural injury and the development of vascular cognitive impairment. However, whether mizagliflozin, a selective SGLT1 inhibitor, can improve the vascular cognitive impairment still unknown. We examined the effects of mizagliflozin on vascular cognitive impairment in mice.Methods: Cerebrovascular hypoperfusion was created using a mouse model of asymmetric common carotid artery surgery (ACAS). Two and/or 4 weeks after ACAS, all experiments were performed.Results: Cerebral blood flow (CBF) was decreased in ACAS compared with sham-operated mice. Mizagliflozin did not reverse the decreased CBF of ACAS mice. Mizagliflozin reversed the ACAS-induced decrease in the latency to fall in a wire hang test of ACAS mice. Moreover, it also reversed the ACAS-induced longer escape latencies in the Morris water maze test of ACAS mice. ACAS increased SGLT1 and interleukin 1β (IL-1β) gene expressions in mouse brains and mizagliflozin did not normalize these gene expressions in ACAS mice. Hematoxylin/eosin staining demonstrated that pyknotic cell death in the ACAS mouse hippocampus was improved in mizagliflozin-treated ACAS mice . In PC12HS cells, IL-1β increased SGLT1 gene expression and decreased survival rates of cells. Mizagliflozin increased the survival rates of IL-1β-treated PC12HS cells.Conclusions: These results suggest that mizagliflozin can improve cerebral hypoperfusion-induced vascular cognitive impairment through the inhibition of neural SGLT1.