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

• Published in: Brain research Vol. 1552; pp. 41 - 54
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 13.03.2014; Elsevier
• Subjects: Aging, Premature - drug therapy; Aging, Premature - enzymology; Aging, Premature - psychology; Amyloid beta-Peptides - analysis; Animals; Anisoles - pharmacology; Anisoles - therapeutic use; Autophagy; Autophagy - drug effects; Biological and medical sciences; CA3 Region, Hippocampal - chemistry; CA3 Region, Hippocampal - drug effects; Cognition Disorders - etiology; Cognition Disorders - prevention & control; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia; Drug Evaluation, Preclinical; Drugs, Chinese Herbal - pharmacology; Enzyme Induction - drug effects; Fundamental and applied biological sciences. Psychology; Lipofuscin - analysis; Long-Term Potentiation - drug effects; Malondialdehyde - analysis; Maze Learning - drug effects; Medical sciences; Mice; Microtubule-Associated Proteins - analysis; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neurology; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Oxidative Stress - drug effects; PC12 Cells; Peptide Fragments - analysis; Rats; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - biosynthesis; rho-Associated Kinases - genetics; rho-Associated Kinases - physiology; RNA Interference; RNA, Small Interfering - pharmacology; ROCK; Superoxide Dismutase - analysis; Synapse; Synapses - drug effects; Synapses - enzymology; Up-Regulation - drug effects; Vertebrates: nervous system and sense organs; β-Asarone; senescence-accelerated-resistant mice; PAS; ROCK; ROCK1; DMSO; LTP; MDA; phosphate-buffered saline; Autophagy; Aβ; DMEM; microtubule associated protein1 light chain 3; dimethyl sulphoxide; MAP2; FBS; Rho associated protein kinase 1; SAMP8; malondialdehyde; hematin and eosin; LC3; β-Asarone; PBS; synaptophysin; Dulbecco׳s modified Eagle׳s medium; asenescence-accelerated prone 8 mice; AD; H&E; amyloid-β; SYN; SOD; traditional Chinese medicine; Alzheimer׳s disease; AGR; microtubule associated protein 2; SAMR1; fetal bovine serum; GAP43; Synapse; superoxide dismutase; periodic acid Schiff; Acori graminei rhizoma; growth-associated protein 43; long-term potentiation; TCM; Dementia; Nervous system diseases; Rodentia; Cerebral disorder; Senile dementia; Vertebrata; Mammalia; Mouse; Animal; Central nervous system disease; Degenerative disease
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2014.01.005

Abstract β-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 β-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 β-asarone on learning and memory. SAMP8 mice at the age of 6 months were intragastrically administered by β-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 β-asarone, and prevents synaptic loss and improved cognitive function of the SAMP8 mice. β-asarone decreased neuronophagia and lipofuscin in the hippocampus of SAMP8 mice, but did not reduce Aβ42 levels and malondialdehyde levels and superoxide dismutase activities. Moreover, suppression of ROCK2 by siRNA significantly reduced the effects of β-asarone on the autophage and synaptic proteins expression in PC12 cells damage induced by Aβ1–40 . Taken together, β-asarone prevents autophagy and synaptic loss by reducing ROCK expression in SAMP8 mice.