Sci. Signal., 14 October 2008
Exciting Changes in Inhibitory ReceptorsIn adult rats, prolonged seizures lead to independent changes in the expression of different subunits of the -aminobutyric acid (GABA) type A receptor (GABAAR), which is the main inhibitory neurotransmitter receptor in the brain, in the dentate gyrus of the hippocampus. These changes in subunit expression, which are accompanied by functional changes in GABAAR-mediated synaptic inhibition, are associated with the development of epilepsy. Seizures increase the abundance of brain-derived neurotrophic factor (BDNF), and Lund et al. now report that both prolonged seizures and BDNF activate the JAK/STAT signaling pathway to decrease transcription of the GABAAR 1 subunit by means of the transcription factors CREB and ICER. Previous research has shown that BDNF increases the abundance of the GABAAR 4 subunit independently of JAK/STAT signaling, suggesting that BDNF regulates GABAergic synaptic transmission through at least two distinct signaling pathways.
Citation: I. V. Lund, Y. Hu, Y. H. Raol, R. S. Benham, R. Faris, S. J. Russek, A. R. Brooks-Kayal, BDNF Selectively Regulates GABAA Receptor Transcription by Activation of the JAK/STAT Pathway. Sci. Signal. 1, ra9 (2008).
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