Deletion of interferon-regulatory factor-1 results in cognitive impairment
Deletion of interferon-regulatory factor-1 results in cognitive impairment
复制标题
干扰素调节因子 1 的缺失会导致认知障碍
DOI：
10.1038/s41440-018-0080-y
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Horiuchi M
中科院分区：
文献类型：
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作者：
Mogi M;Iwanami J;Wang XL;Tsukuda K;Kan-No H;Bai HY;Shan BS;Higaki A;Min LJ;Horiuchi M
神经元中的干扰素调节因子（IRF）-1依赖性基因在缺血性神经元死亡中发挥作用;然而，IRF-1在痴呆中的作用尚未得到充分研究。因此，我们使用由慢性脑灌注不足创建的血管性认知障碍小鼠模型评估IRF-1对认知功能的影响。本研究使用雄性10周龄C57 BL/6（野生型; WT）和IRF-1敲除（IRF-1 KO）小鼠。通过双侧颈总动脉狭窄（BCAS）治疗产生慢性脑低灌注小鼠模型。BCAS 6周后，小鼠接受Morris水迷宫测试，每天5次，持续5天。在Morris水迷宫任务中，与假手术WT小鼠相比，假手术IRF-1 KO小鼠的逃避潜伏期显著延长。然而，BCAS治疗消除了WT和IRF-1 KO小鼠之间空间学习的这种差异。BCAS处理降低了CBF，但BCAS后两个品系之间没有观察到显著差异。假手术IRF-1 KO小鼠显示海马中caspase-1 mRNA表达减少，IRF-2表达增加。血管紧张素II 2型（AT 2）受体的表达，诱导更好的认知功能，由IRF-1调节;然而，没有明显的差异，AT 2受体的表达之间观察到的两个菌株，即使在BCAS。这些结果表明，IRF-1在正常情况下对认知下降具有保护作用;然而，慢性脑低灌注治疗后对认知没有明显影响。
Interferon-regulatory factor (IRF)-1-dependent genes in neurons play a role in ischemic neuronal death; however, the roles of IRF-1 in dementia are not well investigated. Therefore, we assessed the effect of IRF-1 on cognitive function using a vascular cognitive impairment mouse model created by chronic cerebral hypoperfusion. Male 10-week-old C57BL/6 (wild-type; WT) and IRF-1-knockout (IRF-1KO) mice were used in this study. A chronic cerebral hypoperfusion mouse model was generated by bilateral common carotid artery stenosis (BCAS) treatment. After 6 weeks of BCAS, the mice were subjected to the Morris water maze test five times a day for 5 days. In the Morris water maze task, escape latency was significantly prolonged in sham-operated IRF-1KO mice compared with sham-operated WT mice. However, BCAS treatment cancelled such difference in spatial learning between WT and IRF-1KO mice. BCAS treatment decreased CBF, but no significant difference was observed between the two strains after BCAS. Sham-operated IRF-1KO mice showed a decrease in mRNA expression of caspase-1 and an increase in IRF-2 expression in the hippocampus. Expression of angiotensin II type 2 (AT2) receptor, which induces better cognitive function, is regulated by IRF-1; however, no obvious difference in AT2receptor expression was observed between the two strains even after BCAS. These results suggest that IRF-1 has a protective effect on cognitive decline in a normal condition; however, there was no obvious effect on cognition after chronic cerebral hypoperfusion treatment.