title: Tanshinone IIA attenuates Aβ25-35-induced spatial memory impairment via upregulating receptors for activated C kinase1 and inhibiting autophagy in hippocampus.
abstract: OBJECTIVE
  Tanshinone IIA (Tan IIA) may exert significant protective effects against the neurotoxicity induced by β-amyloid protein (Aβ). This study was designed to investigate the possible neuroprotective mechanism of Tan IIA on Aβ25-35-induced spatial memory impairment in mice.
  
  
  METHODS
  After 3 weeks of preventive treatment (Tan IIA or oil), all male Kunming mice were subjected to Aβ25-35(10 μl, intracerebroventricularly (i.c.v.)) to establish the spatial memory impairment model. The Morris water maze (MWM), haematoxylin and eosin staining, real-time PCR and Western blot were performed to determine the ability of spatial memory, neuronal damage and expression of extracellular signal-regulated kinase (ERK), receptors for activated C kinase1 (RACK1) and autophagy-related genes. Additionally, ShRACK1 was used to decrease the level of RACK1 in the hippocampus to test Beclin1 in hippocampus by real-time PCR and Western blot.
  
  
  RESULTS
  Tanshinone IIA (Tan IIA, 80 mg/kg) administration notably protected mice from Aβ25-35-induced spatial memory impairment and neurotoxicity, increased pERK/ERK and the expression of RACK1, and reduced the elevated levels of BECLIN1 and LC3-II/I in the hippocampus. In addition, ShRACK1 i.c.v markedly upregulated BECLIN1 level, but not altered Beclin1 mRNA expression in the hippocampus.
  
  
  CONCLUSIONS
  Tanshinone IIA may exert neuroprotective effects via upregulating RACK1 and inhibiting autophagy in the hippocampus of mice.
authors.affiliation: Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Jiejun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Functional Laboratory, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Shiping
authors.initials: S
authors.lastname: Liao
authors.affiliation: Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China.|Sichuan University '985 Project - Science and Technology Innovation Platform for Novel Drug Development', Sichuan University, Chengdu, Sichuan, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China.|Sichuan University '985 Project - Science and Technology Innovation Platform for Novel Drug Development', Sichuan University, Chengdu, Sichuan, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Wan
mesh_terms: D045784:Abietanes / Q000494:pharmacology* / Q000627:therapeutic use*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000633:toxicity*; D034741:RNA, Small Interfering / Q000494:pharmacology; D000075370:Receptors for Activated C Kinase; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D045784:Abietanes; D016229:Amyloid beta-Peptides; D000071186:Beclin-1; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C090294:RACK1 protein, mouse; D034741:RNA, Small Interfering; D000075370:Receptors for Activated C Kinase; C074636:amyloid beta-protein (25-35); C021751:tanshinone; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Aβ25-35; Tanshinone IIA; autophagy; receptors for activated C kinase1; spatial memory impairment