Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Nervous system--Degeneration; T cells
Nuclear Factor of Activated T-cells (NFAT) is a calcium-responsive transcription factor that orchestrates immune response and cardiovascular development. NFAT is also present in neurons and glia from the Central Nervous System (CNS) where it participates in calcium signaling. In physiological conditions, neuronal NFAT may contribute to the plasticity-related transcriptional regulation. On the other hand, excessive activation of calcium signaling and the subsequent overactivation of NFAT may contribute to neuronal death. To explore the possibility of NFAT-involvement in neuronal death I have determined which components of NFAT signaling are expressed in cultured rat hippocampal or cortical neurons. I found the presence of mRNAs for NFATc1, c3, c4 and c5. I also found that in primary neurons, NFAT transcriptional activity is increased by KCl-mediated depolarization or by chemical trophic deprivation induced by a PI3K/Akt signaling inhibitor LY294002. This transcriptional activity may be blocked by calcineurin inhibitors: cyclosporin A and FK506 and ERK1/2 pathway inhibitor, U0126. Interestingly, overexpression of NFATc4 potentiated apoptosis induced by trophic deprivation in cortical neurons. In summary, these data support the idea that excessive activation of NFAT may produce neuronal death following trophic deprivation. In future, I plan to study the mechanism of NFAT involvement in neuronal death.
Habas, Agata M. 1976-, "The role of nuclear factors of activated T-cells (NFAT) in neuronal death." (2004). Electronic Theses and Dissertations. Paper 555.