Abstract
To investigate the signal mechanism of (-)clausenamide ((-)-3-hydroxy-5- (hydroxyphenyl- 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.
Original language | English (US) |
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Pages (from-to) | 256-262 |
Number of pages | 7 |
Journal | Journal of Asian Natural Products Research |
Volume | 14 |
Issue number | 3 |
DOIs | |
State | Published - 2012 |
Externally published | Yes |
Keywords
- (-)clausenamide
- CREB
- ERK1/2
- Synaptic transmission
- Zif268
ASJC Scopus subject areas
- Analytical Chemistry
- Molecular Medicine
- Pharmacology
- Pharmaceutical Science
- Drug Discovery
- Complementary and alternative medicine
- Organic Chemistry