beta-Asarone prevents autophagy and synaptic loss by reducing ROCK expression in asenescence-accelerated prone 8 mice

作者:Chen Yunbo; Wei Gang; Nie Hui; Lin Yaping; Tian Huijuan; Liu Yu; Yu Xuhua; Cheng Shuyi; Yan Rong; Wang Qi; Liu Dong Hui; Deng Weiye; Lai Yingtao; Zhou Jian Hong; Zhang Sai Xia; Lin Wei Wei; Chen Dong Feng*
来源:Brain Research, 2014, 1552: 41-54.
DOI:10.1016/j.brainres.2014.01.005

摘要

beta-Asarone is an active component of the Acori graminei rhizome that is a traditional Chinese medicine clinically used in treating dementia in China. However, the cognitive effect of beta-asarone and its mechanism has remained elusive. Here, we used asenescence-accelerated prone 8 (SAMP8) mice, which mimic many of the salient features Of Alzheimer's disease (AD), to further investigate whether modulation of the ROCK signaling pathway and/or autophagy, synaptic loss is involved in the effects of beta-asarone on learning and memory. SAMP8 mice at the age of 6 months were intragastrically administered by p-asarone or a vehicle daily for 2 months. Senescence-accelerated-resistant (SAMR1) mice were used as the control. Our results demonstrate that autophagy and ROCK expression were increased significantly in 8 months SAMP8 mice, which were concomitant with that SAMP8 mice at the same age displayed a significant synaptic loss and cognitive deficits. The up-regulation of ROCK expression and autophage in the hippocampus of SAMP8 were significantly reduced by p-asarone, and prevents synaptic loss and improved cognitive function of the SAMP8 mice. beta-asarone decreased neuronophagia and lipofuscin in the hippocampus of SAMP8 mice, but did not reduce A beta 42 levels and malondialdehyde levels and superoxide dismutase activities. Moreover, suppression of ROCK2 by siRNA significantly reduced the effects of p-asarone on the autophage and synaptic proteins expression in PC12 cells damage induced by A beta(1-40 center dot) Taken together, B-asarone prevents autophagy and synaptic loss by reducing ROCK expression in SAMP8 mice.

  • 单位
    广州中医药大学