Tanshinone I enhances learning and memory,and ameliorates memory impairment in mice via the extracellular signal-regulated kinase signalling pathway

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.