Deletion of interferon-regulatory factor-1 results in cognitive impairment

• Published in: Hypertension research 2018-10, Vol.41 (10), p.809-816
• Main Authors: Mogi, Masaki, Iwanami, Jun, Wang, Xiao-Li, Tsukuda, Kana, Kan-No, Harumi, Bai, Hui-Yu, Shan, Bao-Shuai, Higaki, Akinori, Min, Li-Juan, Horiuchi, Masatsugu
• Format: Article
• Language: English
• Subjects: Animal memory; Cognitive ability; Dementia; Rodents
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1038/s41440-018-0080-y

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 (AT ) receptor, which induces better cognitive function, is regulated by IRF-1; however, no obvious difference in AT receptor 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.