NMDA receptors and neuronal survival
Hetman Lab Research Area 2: Signaling of the NMDA receptor-dependent neuronal survival.
N-Methyl-D-Aspartate Receptors (NMDAR) are calcium-permeable ion channels that are activated by the excitatory neurotransmitter glutamate. While their excessive activation induces excitotoxic death of neurons, their moderate activity is critical for neuronal survival at least during brain development. Our laboratory studies the signaling pathways underlying the NMDAR-dependent neuronal survival. We are particularly interested in identifying signaling kinases as well as transcription factors that are critical for this process.
Figure 1. At the pro-survival concentration of 10 mikroM, exogenous NMDA induces nuclear translocation of a calcium regulated transcription factor NFATc4 (Nuclear Factor of Activated T-cells, isoform c4). Primary rat cortical neurons were transfected with an expression plasmid for EGFP-NFATc4 (green) on in vitro day 4. On in vitro day 6, cells were stimulated with NMDA, as indicated. Nuclei were counterstained withch Hoechst-33258 (blue).
To learn more please see:
M.Hetman, G.Kharebava. Survival signaling pathways activated by NMDA receptors. (2006) Current Top. Med. Chem. 6: 787-799 (click here to download a pdf file containing the manuscript)
A.Habas, G.Kharebava, E.Szatmari, and M.Hetman. NMDA neuroprotection against a Phosphatidylinositol-3 Kinase inhibitor, LY294002 by NR2B-mediated suppression of Glycogen Synthase Kinase-3beta-induced apoptosis. (2006) J.Neurochem. 96: 335-348 (PDF file available through )