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.
Keywords: Aβ25-35; Tanshinone IIA; autophagy; receptors for activated C kinase1; spatial memory impairment.
© 2016 Royal Pharmaceutical Society.