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


METHODS
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.


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
Tanshinone I ameliorates the learning and memory impairments induced by diazepam and MK-801 through activation of ERK signalling.
Kim
Dong Hyun
DH
Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, Korea.
Kim
Sunho
S
Jeon
Su Jin
SJ
Son
Kun Ho
KH
Lee
Seungjoo
S
Yoon
Byung Hoon
BH
Cheong
Jae Hoon
JH
Ko
Kwang Ho
KH
Ryu
Jong Hoon
JH
D045784:Abietanes; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007858:Learning / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000188:drug therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation
D045784:Abietanes; D004365:Drugs, Chinese Herbal; D010616:Phenanthrenes; C021751:tanshinone; D048049:Extracellular Signal-Regulated MAP Kinases