title: Compound danshen tablet ameliorated aβ25-35-induced spatial memory impairment in mice via rescuing imbalance between cytokines and neurotrophins.
abstract: BACKGROUND
  Compound Danshen Tablet (CDT), a Traditional Chinese Medicine, has recently been reported to improve spatial cognition in a rat model of Alzheimer's disease. However, in vivo neuroprotective mechanism of the CDT in models of spatial memory impairment is not yet evaluated. The present study is aimed to elucidate the cellular mechanism of CDT on Aβ25-35-induced cognitive impairment in mice.
  
  
  METHODS
  Mice were randomly divided into 5 groups: the control group (sham operated), the Aβ25-35 treated group, the positive drug group, and large and small dosage of the CDT groups, respectively. CDT was administered at a dose of 0.81 g/kg and 0.405 g/kg for 3 weeks. The mice in the positive drug group were treated with 0.4 mg/kg of Huperzine A, whereas the mice of the control and Aβ25-35 treated groups were administrated orally with equivalent saline. After 7 days of preventive treatment, mice were subjected to lateral ventricle injection of Aβ25-35 to establish the mice model of Alzheimer's disease. Spatial memory impairment was evaluated by Morris water maze test. Choline acetyltransferase (ChAT) contents in hippocampus and cortex were quantified by ELISA. The levels of cytokines, receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in hippocampus were measured by RT-PCR and ELISA.
  
  
  RESULTS
  The results showed that Aβ25-35 caused spatial memory impairment as demonstrated by performance in the Morris water maze test. CDT was able to confer a significant improvement in spatial memory, and protect mice from Aβ25-35-induced neurotoxicity. Additionally, CDT also inhibited the increase of TNF-α and IL-6 level, and increased the expression of choline acetyltransferase (ChAT), receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in brain as compared to model mice.
  
  
  CONCLUSIONS
  These findings strongly implicate that CDT may be a useful treatment against learning and memory deficits in mice by rescuing imbalance between cytokines and neurotrophins.
authors.forename: Yan
authors.initials: Y
authors.lastname: Teng
authors.forename: Meng-Qi
authors.initials: MQ
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Li-Tao
authors.initials: LT
authors.lastname: Liu
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhou
authors.forename: Shi-Kun
authors.initials: SK
authors.lastname: Miao
authors.affiliation: Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, PR China. wanlihong1976@sina.com.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Wan
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000075370:Receptors for Activated C Kinase; D027561:Salvia miltiorrhiza / Q000737:chemistry; D065852:Spatial Memory / Q000187:drug effects*; D013607:Tablets; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D015850:Interleukin-6; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C090294:RACK1 protein, mouse; D000075370:Receptors for Activated C Kinase; D013607:Tablets; D014409:Tumor Necrosis Factor-alpha; C074636:amyloid beta-protein (25-35); C028972:dan-shen root extract; D002795:Choline O-Acetyltransferase