The cholinergic system is involved in a broad spectrum of brain function, and its failure has been implicated in Alzheimer＇s disease. Acetylcholine transduces signals through muscarinic and nicotinic acetylcholine re...The cholinergic system is involved in a broad spectrum of brain function, and its failure has been implicated in Alzheimer＇s disease. Acetylcholine transduces signals through muscarinic and nicotinic acetylcholine receptors, both of which influence synaptic plasticity and cognition. However, the mechanisms that relate the rapid gating of nicotinic acetylcholine receptors to persistent changes in brain function have remained elusive. Recent evidence indicates that nicotinic acetylcholine receptors activities affect synaptic morphology and density, which result in persistent rearrangements of neural connectivity. Further investigations of the relationships between nicotinic acetylcholine receptors and rearrangements of neural circuitry in the central nervous system may help understand the pathogenesis of Alzheimer＇s disease.展开更多
Nicotinic acetylcholine receptors （nAChRs） are the targets of neonicotinoids and spinosads, two insecticides used in orchards to effectively control codling moth, Cydia pomonella （L.） （Lepidoptera： Tortricidae）...Nicotinic acetylcholine receptors （nAChRs） are the targets of neonicotinoids and spinosads, two insecticides used in orchards to effectively control codling moth, Cydia pomonella （L.） （Lepidoptera： Tortricidae）. Orchardists in Washington State are concerned about the possibility of codling moth field populations developing resistance to these two insecticides. In an effort to help mitigate this issue, we initiated a project to identify and characterize codling moth nAChR subunits expressed in heads. This study had two main goals; （i） identify transcripts from a codling moth head transcriptome that encode for nAChR subunits, and （ii） determine nAChR subunit expression profiles in various life stages of codling moth. From a codling moth head transcriptome, 24 transcripts encoding for 12 putative nAChR subunit classes were identified and verified by PCR amplification, cloning, and sequence determination. Characterization of the deduced protein sequences encoded by putative nAChR transcripts revealed that they share the distinguishing features of the cys-loop ligand-gated ion channel superfamily with 9 α-type subunits and 3 β- type subunits identified. Phylogenetic analysis comparing these protein sequences to those of other insect nAChR subunits supports the identification of these proteins as nAChR subunits. Stage expression studies determined that there is clear differential expression of many of these subunits throughout the codling moth life cycle. The information from this study will be used in the future to monitor for potential target-site resistance mechanisms to neonicotinoids and spinosads in tolerant codling moth populations.展开更多
In this study, the inhibitory effect of L-theanine, an amino acid derivative of tea, on the rewarding effects of nicotine and its underlying mechanisms of action were studied. We found that L-theanine inhibited the re...In this study, the inhibitory effect of L-theanine, an amino acid derivative of tea, on the rewarding effects of nicotine and its underlying mechanisms of action were studied. We found that L-theanine inhibited the rewarding effects of nicotine in a con- ditioned place preference (CPP) model of the mouse and reduced the excitatory status induced by nicotine in SH-SY5Y cells to the same extent as the nicotine receptor inhibitor dihydro-beta-erythroidine (DH E). Further studies using high performance liquid chromatography, western blotting and immunofluorescence staining analyses showed that L-theanine significantly inhibited nicotine-induced tyrosine hydroxylase (TH) expression and dopamine production in the midbrain of mice. L-theanine treatment also reduced the upregulation of the 4, 2 and 7 nicotine acetylcholine receptor (nAChR) subunits induced by nico- tine in mouse brain regions that related to the dopamine reward pathway, thus decreasing the number of cells that could react to nicotine. In addition, L-theanine treatment inhibited nicotine-induced c-Fos expression in the reward circuit related areas of the mouse brain. Knockdown of c-Fos by siRNA inhibited the excitatory status of cells but not the upregulation of TH induced by nicotine in SH-SY5Y cells. Overall, the present study showed that L-theanine reduced the nicotine-induced reward effects via inhibition of the nAChR-dopamine reward pathway. These results may offer new therapeutic strategies for treatment of tobacco addiction.展开更多
基金supported by the Takeda Science Foundation and JSPS KAKENHI Grant Number 19590247
文摘The cholinergic system is involved in a broad spectrum of brain function, and its failure has been implicated in Alzheimer＇s disease. Acetylcholine transduces signals through muscarinic and nicotinic acetylcholine receptors, both of which influence synaptic plasticity and cognition. However, the mechanisms that relate the rapid gating of nicotinic acetylcholine receptors to persistent changes in brain function have remained elusive. Recent evidence indicates that nicotinic acetylcholine receptors activities affect synaptic morphology and density, which result in persistent rearrangements of neural connectivity. Further investigations of the relationships between nicotinic acetylcholine receptors and rearrangements of neural circuitry in the central nervous system may help understand the pathogenesis of Alzheimer＇s disease.
基金We thank Drs. Man-Yeon Choi and Rodney Cooper for critical review of this manuscript. We are most grate- ful to Laura Willett, Kim Shannon, and Karolynn Tom for maintenance of the codling moth colony. Dr. MichaelParra （Heritage University） is thanked for his helpful dis- cussions and comments. This work was supported by a grant from the Washington Tree Fruit Research Commis- sion （awarded to SFG, CP-13-101） and a grant from the Research Experience for Undergraduates program of the National Science Foundation （awarded to Nina Barcenas, Heritage University, NSF-REU Award# 1156603）.
文摘Nicotinic acetylcholine receptors （nAChRs） are the targets of neonicotinoids and spinosads, two insecticides used in orchards to effectively control codling moth, Cydia pomonella （L.） （Lepidoptera： Tortricidae）. Orchardists in Washington State are concerned about the possibility of codling moth field populations developing resistance to these two insecticides. In an effort to help mitigate this issue, we initiated a project to identify and characterize codling moth nAChR subunits expressed in heads. This study had two main goals; （i） identify transcripts from a codling moth head transcriptome that encode for nAChR subunits, and （ii） determine nAChR subunit expression profiles in various life stages of codling moth. From a codling moth head transcriptome, 24 transcripts encoding for 12 putative nAChR subunit classes were identified and verified by PCR amplification, cloning, and sequence determination. Characterization of the deduced protein sequences encoded by putative nAChR transcripts revealed that they share the distinguishing features of the cys-loop ligand-gated ion channel superfamily with 9 α-type subunits and 3 β- type subunits identified. Phylogenetic analysis comparing these protein sequences to those of other insect nAChR subunits supports the identification of these proteins as nAChR subunits. Stage expression studies determined that there is clear differential expression of many of these subunits throughout the codling moth life cycle. The information from this study will be used in the future to monitor for potential target-site resistance mechanisms to neonicotinoids and spinosads in tolerant codling moth populations.
基金supported by the National Natural Science Foundation of China (Grant No. 30870587)National Basic Research Program of China from the Department of Science and Technology of China(Grant No. 2006CB500700)
文摘In this study, the inhibitory effect of L-theanine, an amino acid derivative of tea, on the rewarding effects of nicotine and its underlying mechanisms of action were studied. We found that L-theanine inhibited the rewarding effects of nicotine in a con- ditioned place preference (CPP) model of the mouse and reduced the excitatory status induced by nicotine in SH-SY5Y cells to the same extent as the nicotine receptor inhibitor dihydro-beta-erythroidine (DH E). Further studies using high performance liquid chromatography, western blotting and immunofluorescence staining analyses showed that L-theanine significantly inhibited nicotine-induced tyrosine hydroxylase (TH) expression and dopamine production in the midbrain of mice. L-theanine treatment also reduced the upregulation of the 4, 2 and 7 nicotine acetylcholine receptor (nAChR) subunits induced by nico- tine in mouse brain regions that related to the dopamine reward pathway, thus decreasing the number of cells that could react to nicotine. In addition, L-theanine treatment inhibited nicotine-induced c-Fos expression in the reward circuit related areas of the mouse brain. Knockdown of c-Fos by siRNA inhibited the excitatory status of cells but not the upregulation of TH induced by nicotine in SH-SY5Y cells. Overall, the present study showed that L-theanine reduced the nicotine-induced reward effects via inhibition of the nAChR-dopamine reward pathway. These results may offer new therapeutic strategies for treatment of tobacco addiction.
文摘目的探讨神经元烟碱受体(neuronal nicotinic acetyl-choline receptor,nnAchR)与吸入麻醉药恩氟烷催眠、遗忘作用的关系。方法小鼠腹腔注射不同剂量的恩氟烷(2.2,0.4ml.kg-1)建立模型,催醒实验中观察不同剂量的烟碱(nicotine,N)侧脑室注射(intracerebroventricular,icv)对小鼠睡眠时间(sleeping time,ST)的影响;跳台、避暗实验中观察不同剂量的烟碱icv对跳台潜伏期(step down latency,SDL)、步入潜伏期(step through latency,STL)和错误次数的影响。自主活动实验观察恩氟烷(0.4ml.kg-1)对小鼠自主活动次数的影响。结果和对照组相比,脑室注射烟碱能缩短恩氟烷麻醉小鼠的ST,延长恩氟烷所致记忆障碍小鼠的SDL、STL,减少错误次数。0.4ml.kg-1腹腔注射对小鼠自主活动无明显影响。结论本实验结果提示脑内的神经元烟碱受体是恩氟烷催眠、遗忘作用的重要靶位之一。
