title: Tong Luo Jiu Nao ameliorates Aβ1-40-induced cognitive impairment on adaptive behavior learning by modulating ERK/CaMKII/CREB signaling in the hippocampus.
abstract: BACKGROUND
  Tong Luo Jiu Nao (TLJN), a modern formula of Chinese medicine extracts on the basis of Traditional Chinese Medicine theory, has been used to treat dementia. The present study aimed to investigate its ameliorating effects on Aβ1-40-induced cognitive impairment in rats using a series of novel reward-directed instrumental learning (RDIL) tasks, and to determine its possible mechanism of action.
  
  
  METHODS
  Rats were pretreated with TLJN extract (0.9 and 1.8 g/kg, p.o.) for 10 daysbefore surgery, and were trained to gain reward reinforcement by lever pressing at the meantime. Thereafter, rats received a bilateral microinjection of Aβ1-40 in CA1 regions of the hippocampus. Cognitive performance was evaluated with the goal directed (higher response ratio) and habit (visual signal discrimination and extinction) learning tasks, as well as on the levels of biochemical parameters and molecules.
  
  
  RESULTS
  Our findings first demonstrated that TLJN can improve Aβ1-40-induced amnesia in RDIL via enhancing the comprehension of action-outcome association and the utilization of cue information to guide behavior. Then, its ameliorating effects should attribute to the modulation of ERK/CaMKII/CREB signaling in the hippocampus.
  
  
  CONCLUSIONS
  TLJN can markedly enhance cognitions of Aβ1-40 microinjection animal model in adaptive behavioral tasks. It has the potential, possibly as complementary and alternative therapy, to prevent and/or delay the deterioration of cognitive impairment in AD.
authors.affiliation: Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Malianwa North Road No. 151, Beijing, 100193, China. zhe.shield@gmail.com.|Division of Stem Cell Regulation and Application, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. zhe.shield@gmail.com.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Malianwa North Road No. 151, Beijing, 100193, China. lucong198912@126.com.
authors.forename: Cong
authors.initials: C
authors.lastname: Lu
authors.affiliation: Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Malianwa North Road No. 151, Beijing, 100193, China. supering_sun@126.com.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Sun
authors.affiliation: Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Malianwa North Road No. 151, Beijing, 100193, China. luyiwangqiong@163.com.|Division of Stem Cell Regulation and Application, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. luyiwangqiong@163.com.|China Astronaut Research and Training Center, Yuanmingyuan West Road No. 1, Beijing, 100094, China. luyiwangqiong@163.com.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: China Astronaut Research and Training Center, Yuanmingyuan West Road No. 1, Beijing, 100094, China. tigercsg@163.com.
authors.forename: Shanguang
authors.initials: S
authors.lastname: Chen
authors.affiliation: China Astronaut Research and Training Center, Yuanmingyuan West Road No. 1, Beijing, 100094, China. yinghuidd@vip.sina.com.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.affiliation: China Astronaut Research and Training Center, Yuanmingyuan West Road No. 1, Beijing, 100094, China. linaqu@263.net.
authors.forename: Lina
authors.initials: L
authors.lastname: Qu
authors.affiliation: Division of Stem Cell Regulation and Application, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. linglingchen@126.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Division of Stem Cell Regulation and Application, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. bulanlan216@163.com.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Bu
authors.affiliation: Division of Stem Cell Regulation and Application, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. dfliao@aliyun.com.
authors.forename: Duanfang
authors.initials: D
authors.lastname: Liao
authors.affiliation: Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Malianwa North Road No. 151, Beijing, 100193, China. liuxinmin@hotmail.com.|Division of Stem Cell Regulation and Application, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. liuxinmin@hotmail.com.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Liu
mesh_terms: D000223:Adaptation, Psychological; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000647:Amnesia / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000009:adverse effects / Q000378:metabolism; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003704:Dementia; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D030141:Feedback, Psychological / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007858:Learning / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008516:Medicine, Chinese Traditional; D010446:Peptide Fragments / Q000009:adverse effects / Q000378:metabolism; D008517:Phytotherapy; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D017362:Cyclic AMP Response Element-Binding Protein; D004365:Drugs, Chinese Herbal; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C528243:tongluo jiunao; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2