SGLT1 participates in the development of vascular cognitive impairment in a mouse model of small vessel disease. (14th May 2020)

• Record Type: Journal Article
• Authors: Ishida, Nanae; Saito, Maki; Sato, Sachiko; Koepsell, Hermann; Taira, Eiichi; Hirose, Masamichi
• Is Part Of: Neuroscience letters. Volume 727(2020)
• Publication Date: 2020-05-14
• Subjects: SGLT1 -- Vascular cognitive impairment -- Small vessel dementia; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2020.134929
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Cerebral hypoperfusion increased SGLT1 but not GLUT1 and 3 gene expression. Deletion of SGLT1 gene protects against cognitive impairment. Deletion of SGLT1 gene reduces several inflammatory cytokine gene expressions. Deletion of SGLT1 gene reduces MCP-1 gene expression. Abstract: Sodium/glucose cotransporter 1 (SGLT1) participates in ischemia-reperfusion-induced cerebral injury. However, whether SGLT1 participates in the development of small vessel disease induced-vascular cognitive impairment is unknown. We examined the roles of SGLT1 in the development of vascular cognitive impairment in a mouse model of small vessel disease. Small vessel disease was created by placement of an ameroid constrictor around the right common carotid artery (CCA) and placement of a microcoil around the left CCA (ACAS) in wild-type (WT) and SGLT1-knock out (KO) mice. Two and/or 4 weeks after ACAS, all experiments were performed. Hematoxylin/eosin staining demonstrated that the number of pyknotic cell deaths was greater in the ACAS WT than ACAS SGLT1-KO hippocampus. The latency to fall in a wire hang test was significantly shorter in ACAS than sham-operated WT mice, whereas it was similar between ACAS and sham-operated SGLT1-KO mice. The Morris water maze test revealed that ACAS WT mice exhibited longer escape latencies than ACAS SGLT1-KO mice. ACAS significantly increased SGLT1 gene expression in WT mouse brains. Gene expressions of MCP-1, IL-1β, TNF-α, and IL-6 were increased in ACAS WT compared with sham-operated WT mouse brains. Their increased gene expressions were significantly decreased in ACAS SGLT1-KO compared with ACAS WT mice. These results suggest that SGLT1 plays important roles in the development of small vessel dementia.