Improvement of cognitive decline by cerebral AT2 receptor and HDAC2 inhibition

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19974
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Ehime University
• Principal Investigator: Iwanami Jun 愛媛大学, 医学系研究科, 助教 (90624792)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 認知機能 / 血管性認知症 / レニン・アンジオテンシン系 / エピジェネティクス / アンジオテンシンII2型受容体 / ヒストン脱アセチル化酵素２

Outline of Final Research Achievements

Cerebral histone deacetylase (HDAC) 2 has been highlighted in terms of epigenetic modulation of cognitive function. We recently reported that angiotensin II type 2 (AT2) receptor stimulation improved cognitive decline in the mouse model （BCAS) of vascular dementia. These results led us to examine the effects of HDAC on AT2 receptor-mediated improvement of cognitive decline. HDAC2 protein level in the hippocampus did not differ between WT and AT2KO mice at 10 weeks of age, whereas HDAC2 of AT2KO mice at 20 weeks of age was higher compared with that of WT mice. Cognitive impairment after BCAS was more marked in AT2KO mice. Treatment with HDAC inhibitor attenuated BCAS-induced prolongation of escape latency in the Morris water maze test both in WT and AT2KO mice; however this effect of HDAC inhibitor was more marked in AT2KO mice. We speculate that modulation of cerebral AT2 receptor could be new therapeutic tool to prevent cognitive impairment via epigenetic abnormalities.

Free Research Field

医歯薬学