(-)Clausenamide facilitates synaptic transmission at hippocampal Schaffer collateral-CA1 synapses.

Abstract

Clausenamide is a chiral compound isolated from leaves of the traditional Chinese herb Clausena lansium (lour) Skeels. It has been shown that (-)clausenamide, but not (+)clausenamide, improved learning and memory in amnesia animal models. However, the precise mechanism of clausenamide's actions remains unknown. Here we used an electrophysiological approach to observe the effect of (-)clausenamide on facilitating field excitatory postsynaptic potential (f-EPSP) in the CA1 area of hippocampal slices from rats. The results showed that (-)clausenamide enhanced synaptic transmission at doses 0.1, 1 and 10 μM. The increase of f-EPSP induced by (-)clausenamide was completely inhibited by preincubation with nimodipine (L-voltage-dependent calcium channel blocker, 10 μM), but there was no change when nimodipine was added after (-)clausenamide application. However, ryanodine (ryanodine receptors blocker, 100 μM) attenuated the slope of f-EPSP before or after (-)clausenamide incubation. The data suggested that (-)clausenamide promoted calcium influx to trigger intracellular calcium release which was responsible for potentiating synaptic transmission. Intracellular calcium release induced by (-)clausenamide promoted the activation of CaMKIIα at concentrations of 0.1, 1 and 10 μM, and pretreatment with KN93 (CaMKIIα inhibitor, 10 μM) completely blocked the enhancement of synaptic transmission induced by (-)clausenamide. cAMP response element-binding protein (CREB) was activated by (-)clausenamide and inhibited by KN93 preincubation, but H89 (PKA inhibitor, 10 μM) had no effect, indicating that (-)clausenamide facilitated synaptic transmission by a PKA-independent pathway. Collectively, (-)clausenamide facilitated synaptic transmission by promoting calcium influx to trigger intracellular calcium release, subsequently activating CaMKIIα-CREB signal pathway.

• Authors: Na Ning, Jin-Feng Hu, Jian-Dong Sun, Ning Han, Jun-Tian Zhang, Nai-Hong Chen
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 682 Issue 1-3 Pg. 50-5 (May 05 2012) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 22366429 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Cyclic AMP Response Element-Binding Protein
• Lactams
• Lignans
• clausenamide
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Calcium

Topics

• Animals
• Axons (drug effects, metabolism)
• CA1 Region, Hippocampal (cytology, drug effects, metabolism, physiology)
• Calcium (metabolism)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (metabolism)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Excitatory Postsynaptic Potentials (drug effects)
• In Vitro Techniques
• Lactams (pharmacology)
• Lignans (pharmacology)
• Male
• Memory (drug effects, physiology)
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Phosphorylation (drug effects)
• Rats
• Rats, Wistar
• Synapses (drug effects, metabolism)
• Synaptic Transmission (drug effects)