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The mechanism of tianeptine's neurotrophic effect on hippocampal neuron

7AP5-5

Chu, C.; Shui, H.; Shieh, J.; Wang, J.; Ho, S.

European Journal of Anaesthesiology (EJA): May-June 2008 - Volume 25 - Issue - p 102–103
Abstracts and Programme, EUROANAESTHESIA 2008: Neurosciences
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Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan

Background and Goal of Study: Tianeptine is a clinically effective antidepressant that has been found capable of preventing and reversing stress- and glucocorticoid-induced changes in hippocampal morphology that result in cognitive impairment. Therefore, tianeptine has a potential neuroprotective effect. However, whether tianeptine promote the neurite growth or synaptic formation has never been studied on a cultured hippocampal model. In addition, the mechanism of its neuroprotective effect remains unknown.

Materials and Methods: On hippocampal neuron primary culture, we investigated whether Tianeptine, as compared with vehicle or nerve growth factor β, could enhance neuritic arborization, outgrowth and synaptic formation. The signaling pathway of the neurotrophic effect of tianeptine on the structural plasticity was studied by evaluation of the possible kinases phosphorylation after treatment. Also specific kinase antagonists was pre-treated to confirm the signaling pathway.

Results and Discussion: We found that tianeptine dose dependently (0, 0.3, 0.6, 1, 5,and 10 μg/ml) enhanced the dendritic arborization and synaptic formation. The neurotrophic effects were as effective as nerve growth factor β. At the same time, tianeptine dose dependently up regulated the expression of cytoskeletal protein MAP 2, Neuro filament L and synaptophysin. Tianeptine at 10μg/ml significantly phosphorylated CaMK II, and pretreating with CaMK II antagonist (KN93) decreased the neutrophic effect of tianeptine.

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Conclusion(s): Tianeptine had neurotrophic effects as effective as nerve growth factor β by activation of CaMK II phosphorylation.

© 2008 European Society of Anaesthesiology