Activation of ERK1/2-CREB pathway during potentiating synaptic transmission of ( − )clausenamide in rat dentate gyrus

Abstract

To investigate the signal mechanism of ( − )clausenamide (( − )-3-hydroxy-5-(hydroxy-phenyl-methyl)-1-methyl-4-phenyl-pyrrolidin-2-one, 1) and for understanding its effect on synaptic transmission, electrophysiological recording was done for basal synaptic transmission determination. Western blot analysis was employed to examine the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP responsive element-binding protein (CREB). Immunohistochemistry and tissue in situ hybridization were applied to detect the expression of Zif268. The results showed that ( − )clausenamide (1) increased the population spike of hippocampal dentate gyrus. The phosphorylation of ERK1/2 in hippocampus and cortex was increased and reached the maximum at 5 min and 30 min, respectively. ( − )Clausenamide (1) promoted the phosphorylation of CREB, the downstream protein of ERK1/2. The expression of Zif268 protein and mRNA increased in both hippocampal dentate gyrus and cortex. Therefore, ( − )clausenamide (1) activated the ERK1/2-CREB pathway, which may provide an explanation for its effect on potentiating synaptic transmission and improving learning and memory.

Keywords:

• ( − )clausenamide
• synaptic transmission
• ERK1/2
• CREB
• Zif268

Acknowledgements

The authors thank Prof Daniel Nathans for providing the zif268 cDNA probe. This work was financially supported by the National Natural Science Foundation of China (Nos. 30801527, 30973887, U832008, and 90713045).

Notes

^1. These two authors contributed equally to this work.