| Title | Knockdown of the Aryl Hydrocarbon Receptor Attenuates Excitotoxicity and Enhances NMDA-Induced BDNF Expression in Cortical Neurons. | | Author(s) | Lin CH, Chen CC, Chou CM, Wang CY, Hung CC, Chen JY, Chang HW, Chen YC, Yeh GC, Lee YH | | Institution | Division of Cell Physiology and Neuroscience, Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan. | | Source | J Neurochem 2009 Aug 27. | | Abstract | Abstract NMDA receptors play dual and opposing roles in neuronal survival by mediating the activity-dependent neurotrophic signaling and excitotoxic cell death via synaptic and extrasynaptic receptors, respectively. In this study, we demonstrate that the aryl hydrocarbon receptor (AhR), also known as the dioxin receptor, is involved in the expression and the opposing activities of NMDA receptors. In primary cultured cortical neurons, we found that NMDA excitotoxicity is significantly enhanced by an AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and AhR knockdown with siRNA significantly reduces NMDA excitotoxicity. AhR knockdown also significantly reduces NMDA-increased intracellular calcium concentration, NMDA receptor expression and surface presentation, and moderately decreased the NMDA receptor-mediated spontaneous as well as miniature EPSCs. However, AhR knockdown significantly enhances the bath NMDA application- but not synaptic NMDA receptor-induced BDNF gene expression, and activating AhR reduces the bath NMDA-induced BDNF expression. Furthermore, AhR knockdown reveals the calcium dependency of NMDA-induced BDNF expression and the binding activity of CREB and its calcium-dependent coactivator CBP to the BDNF promoter upon NMDA treatment. Together, our results suggest that AhR opposingly regulates NMDA receptor-mediated excitotoxicity and neurotrophism possibly by differentially regulating the expression of synaptic and extrasynaptic NMDA receptors. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19712055 |
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