Alpha-asarone improves striatal cholinergic function and locomotor hyperactivity in Fmr1 knockout mice.
Hyperactivity is a symptom found in several neurological and psychiatric disorders, including Fragile X syndrome (FXS). The animal model of FXS, fragile X mental retardation gene (Fmr1) knockout (KO) mouse, exhibits robust locomotor hyperactivity. Alpha (α)-asarone, a major bioactive component isolated from Acorus gramineus, has been shown in previous studies to improve various disease conditions including central nervous system disorders. In this study, we show that treatment with α-asarone alleviates locomotor hyperactivity in Fmr1 KO mice. To elucidate the mechanism underlying this improvement, we evaluated the expressions of various cholinergic markers, as well as acetylcholinesterase (AChE) activity and acetylcholine (ACh) levels, in the striatum of Fmr1 KO mice. We also analyzed the AChE-inhibitory activity of α-asarone. Striatal samples from Fmr1 KO mice showed decreased m1 muscarinic acetylcholine receptor (m1 mAChR) expression, increased AChE activity, and reduced ACh levels. Treatment with α-asarone improved m1 mAChR expression and ACh levels, and attenuated the increased AChE activity. In addition, α-asarone dose-dependently inhibited AChE activity in vitro. These results indicate that direct inhibition of AChE activity and up-regulation of m1 mAChR expression in the striatum might contribute to the beneficial effects of α-asarone on locomotor hyperactivity in Fmr1 KO mice. These findings might improve understanding of the neurobiological mechanisms responsible for locomotor hyperactivity.
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province, The Ministry of Education, Institute of Neuroscience, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, 510260, China.
Guozhen
G
Qiu
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province, The Ministry of Education, Institute of Neuroscience, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, 510260, China.
Shengqiang
S
Chen
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province, The Ministry of Education, Institute of Neuroscience, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, 510260, China.
Jialing
J
Guo
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province, The Ministry of Education, Institute of Neuroscience, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, 510260, China.
Jie
J
Wu
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province, The Ministry of Education, Institute of Neuroscience, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, 510260, China; Department of Neurology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, Guangdong Province, China. Electronic address: yyh168@sina.com.
Yong-Hong
YH
Yi
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism*; D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000502:physiology*; D005600:Fragile X Syndrome / Q000378:metabolism / Q000523:psychology; D006948:Hyperkinesis / Q000378:metabolism* / Q000517:prevention & control; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011976:Receptors, Muscarinic / Q000378:metabolism*
D000109:Acetylcholine; D000110:Acetylcholinesterase; D000081248:Allylbenzene Derivatives; D000840:Anisoles; D051860:Fragile X Messenger Ribonucleoprotein 1; D011976:Receptors, Muscarinic; C497684:Fmr1 protein, mouse; C012195:asarone
AChE; Alpha-asarone; Fmr1 KO mice; Locomotor hyperactivity; m1 mAChR