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A new relationship between brain derived neurotrophic factor and inflammatory signaling
Date:10/22/2008

(Boston)-In the October 14th edition of Science Signaling researchers at Boston University School of Medicine (BUSM), The Children's Hospital of Philadelphia/University of Pennsylvania School of Medicine and The University of Colorado Denver School of Medicine have shown that the development of epilepsy in adult rats is linked to functional changes in the expression of alpha 1 containing GABA-A receptors, the main inhibitory neurotransmitter receptor in the brain, that may be dependent upon BDNF-induced activation of the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway. Activation of the JAK/STAT pathway has previously been shown to be dependent upon cytokines and is implicated in a large number of inflammatory diseases.

The multiple subunits of the GABA-A receptor show developmental and region specific expression in the brain and produce a diverse set of functional receptor isoforms. Drs. Shelley Russek, a molecular neuroscientist/pharmacologist from Boston University School of Medicine and Dr. Amy Brooks-Kayal, a pediatric neurologist researcher from the University of Colorado Denver School of Medicine, believe that changes in inhibitory receptors in a portion of the brain known as the dentate gyrus may be crtically important to the development of temporal lobe epilepsy, the most common type of epilepsy in children and adults. Decrease of GABA-A receptors containing alpha 1 subunits at the synapse, and increase of receptors containing alpha 4, has been associated with spontaneous seizures. The senior authors recent publication associates the marked rise in BDNF that accompanies prolonged seizures with a specific decrease in the levels of alpha 1 that is reversed upon in vivo delivery of a JAK/STAT pathway inhibitor. Alpha 1 gene regulation is dependent upon the induction of a transcriptional repressor called inducible cAMP early repressor (ICER) that binds to the alpha 1 gene in coordination with the cAMP regul
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Contact: Gina Digravio
gina.digravio@bmc.org
617-638-8491
Boston University
Source:Eurekalert

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