Basic Research
Effects of Isopimaric Acid on cognitive handicap and synaptic plasticity in APP/PS1 mice
Wang Li, Tang Zuoqing, Jia Jun, Jiao Jinsong, Liu Zunjing, Li Xudong, Duan Xiaohui, Dong Mingrui, Xia Qisheng, Wang Kang
Published 2016-12-20
Cite as Chin J Behav Med & Brain Sci, 2016,25(12): 1057-1062. DOI: 10.3760/cma.j.issn.1674-6554.2016.12.001
Abstract
ObjectiveTo investigate the protective effects of isopimaric acid (ISO), the BKCa channel activator, on cognitive function and synaptic plasticity in APP/PS1 mice.
MethodsAlzet osmotic pump was loaded with ISO or DMSO only and assembled with ALZET Brain Infusion Kit III. The cannula was implanted into the lateral ventricle of 4-month-old male APP/PS1 mice or matched wild type (WT) mice. Two weeks later, open field test and Morris water maze were conducted. Paired-pulse facilitation (PPF) and TBS-induced long-term potentiation (LTP) were recorded in CA1 region of hippocampus.
ResultsThe open field test showed that there was no significant difference among the four groups in spontaneous activities and vertical plane movement distance within 30 minutes. Floor plane movement distance was significantly greater in APP/PS1+ DMSO group than that in WT+ DMSO group(P<0.05). Compared with the WT+ DMSO group, APP/PS1+ DMSO group had significantly longer escape latency from the third to fifth day and lower percentage of time spent in the target quadrant ((43.27±3.24)% vs (34.19±2.56)%) and the number of crossing through the platform ((4.25±0.66)times vs (1.93±0.33)times)(P<0.05). Compared with the APP/PS1+ DMSO group, the APP/PS1+ ISO group had significantly shorter escape latency from the fourth to fifth day and higher percentage of time spent in the target quadrant ((46.16±3.51)%) and the number of crossing through the platform ((3.41±0.34) times) (P<0.05). PPF in APP/PS1+ DMSO group significantly reduced compared with that in WT+ DMSO group at 30-50ms interstimulus interval(P<0.05). PPF in APP/PS1+ ISO group((224.50±13.79)%) was significantly augment compared with APP/PS1+ DMSO ((174.99±6.68)%) group at 40 ms interstimulus interval (P<0.05). The LTP at 60 min post-TBS was significantly smaller in the APP/PS1+ DMSO group ((135.19±1.32)%) than that in the WT+ DMSO group ((172.17±4.15)%)(P<0.001). The LTP of the APP/PS1+ ISO group((160.48±1.19)%) became significantly increased compared with that in the APP/PS1+ DMSO group(P<0.001).
ConclusionBKCa channel activator ISO improve the learning and memory function of APP/PS1 mice by promoting PPF and increasing LTP to recover synaptic plasticity in the hippocampus.
Key words:
Alzheimer’s disease; APP/PS1; Isopimaric acid; Synaptic plasticity; BKCa channel
Contributor Information
Wang Li
Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China
Tang Zuoqing
Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
Jia Jun
Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
Jiao Jinsong
Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China
Liu Zunjing
Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China
Li Xudong
Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China
Duan Xiaohui
Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China
Dong Mingrui
Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China
Xia Qisheng
Department of Biochemistry, China-Japan Friendship Hospital, Beijing 100029, China
Wang Kang
Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China
