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Tanshinone I enhances learning and memory, and ameliorates memory impairment in mice via the extracellular signal‐regulated kinase signalling pathway
Author(s) -
Kim Dong Hyun,
Kim Sunho,
Jeon Su Jin,
Son Kun Ho,
Lee Seungjoo,
Yoon Byung Hoon,
Cheong Jae Hoon,
Ko Kwang Ho,
Ryu Jong Hoon
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00378.x
Subject(s) - creb , mapk/erk pathway , western blot , kinase , hippocampus , memory impairment , dizocilpine , pharmacology , protein kinase a , chemistry , neuroscience , medicine , psychology , nmda receptor , cognition , receptor , biochemistry , transcription factor , gene
Background and purpose: The intracellular signalling kinase, extracellular signal‐regulated kinase 1/2 (ERK1/2) is required for new memory formation, suggesting that control of ERK signalling might be a target for the treatment of cognitive dysfunction. Previously, we reported that tanshinone congeners have ameliorating effects on drug‐induced memory impairment in mice. Here, we have investigated possible modes of action of tanshinone I on learning and memory, associated with ERK phosphorylation. Experimental approach: Using immunohistochemical, Western blot techniques, and behavioural testing, we studied the effect of tanshinone I on memory impairment induced by diazepam or dizocilpine (MK‐801) in mice. Key results: Tanshinone I (2 or 4 mg·kg −1 , p.o.) increased latency times versus vehicle‐treated control group in the passive avoidance task. Western blot analysis and immunohistochemical data showed that tanshinone I (4 mg·kg −1 ) increased levels of phosphorylated cAMP response element binding protein (pCREB) and phosphorylated ERK (pERK) in the hippocampus. These increases in pCREB and pERK were blocked by U0126 (inhibitor of ERK1/2), which also prevented the increase in passive avoidance task latency time after tanshinone I. In models of learning and memory impairment induced by diazepam and MK‐801, tanshinone I (4 mg·kg −1 ) reversed learning and memory impairments detected by the passive avoidance test. Western blot analysis showed that tanshinone I reversed the diazepam‐ and MK‐801‐induced inhibitions of ERK and CREB activation in hippocampal tissues. These effects were also blocked by U0126. Conclusions and implications: Tanshinone I ameliorates the learning and memory impairments induced by diazepam and MK‐801 through activation of ERK signalling.