SGLT1 participates in the development of vascular cognitive impairment in a mouse model of small vessel disease
SGLT1 participates in the development of vascular cognitive impairment in a mouse model of small vessel disease
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DOI：
10.1016/j.neulet.2020.134929
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发表时间：
2020-05-14
影响因子：
2.5
通讯作者：
Hirose, Masamichi
中科院分区：
文献类型：
--
作者：
Ishida, Nanae;Saito, Maki;Hirose, Masamichi
钠/葡萄糖共转运体1(SGLT1)参与脑缺血再灌注损伤。然而，SGLT1是否参与小血管疾病所致的血管性认知功能障碍尚不清楚。我们在小血管疾病的小鼠模型中研究了SGLT1在血管认知障碍发展中的作用。在野生型(WT)和SGLT1基因敲除(KO)小鼠的右侧颈总动脉(CCA)周围放置一条无菌缩窄管，在左侧CCA(ACAS)周围放置一个微线圈，造成小血管疾病。ACAS后2周和/或4周，所有实验均完成。苏木精-伊红染色显示，ACAS WT组固缩细胞死亡数明显多于ACAS SGLT1-KO组。在钢丝悬挂测试中，ACAS组小鼠的跌倒潜伏期显著短于假手术的WT小鼠，而ACAS和假手术的SGLT1-KO小鼠的跌倒潜伏期相似。Morris水迷宫实验显示ACAS WT小鼠较ACAS SGLT1-KO小鼠表现出更长的逃避潜伏期。ACAs可显著增加WT小鼠脑组织SGLT1基因的表达。ACAS WT组小鼠脑内MCP-1、IL-1β、TNF-α、IL-6基因表达较假手术组升高。与ACAS WT小鼠相比，ACAS SGLT1-KO小鼠上调的基因表达水平显著降低。这些结果提示SGLT1在小血管性痴呆的发生发展中起重要作用。
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-1 beta, TNF-alpha, 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.