Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5829687 | European Journal of Pharmacology | 2012 | 6 Pages |
Abstract
Clausenamide is a chiral compound isolated from leaves of the traditional Chinese herb Clausena lansium (lour) Skeels. It has been shown that (â)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 (â)clausenamide on facilitating field excitatory postsynaptic potential (f-EPSP) in the CA1 area of hippocampal slices from rats. The results showed that (â)clausenamide enhanced synaptic transmission at doses 0.1, 1 and 10 μM. The increase of f-EPSP induced by (â)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 (â)clausenamide application. However, ryanodine (ryanodine receptors blocker, 100 μM) attenuated the slope of f-EPSP before or after (â)clausenamide incubation. The data suggested that (â)clausenamide promoted calcium influx to trigger intracellular calcium release which was responsible for potentiating synaptic transmission. Intracellular calcium release induced by (â)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 (â)clausenamide. cAMP response element-binding protein (CREB) was activated by (â)clausenamide and inhibited by KN93 preincubation, but H89 (PKA inhibitor, 10 μM) had no effect, indicating that (â)clausenamide facilitated synaptic transmission by a PKA-independent pathway. Collectively, (â)clausenamide facilitated synaptic transmission by promoting calcium influx to trigger intracellular calcium release, subsequently activating CaMKIIα-CREB signal pathway.
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Authors
Na Ning, Jin-Feng Hu, Jian-Dong Sun, Ning Han, Jun-Tian Zhang, Nai-Hong Chen,