Jiejun Zhu1, Shiping Liao2, Liming Zhou1,3, Lihong Wan1,3. 1. Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China. 2. Functional Laboratory, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China. 3. Sichuan University '985 Project - Science and Technology Innovation Platform for Novel Drug Development', Sichuan University, Chengdu, Sichuan, China.
Abstract
OBJECTIVES: 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. KEY FINDINGS: 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.
OBJECTIVES: 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. KEY FINDINGS: 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.