title: GABA(A) receptor regulation after experimental traumatic brain injury.
abstract: The gamma-aminobutyric acid (GABA) type A receptor (GABA(A)R) is responsible for most fast synaptic inhibition in the adult brain. The GABA(A)R protein is composed of multiple subunits that determine the distribution, properties, and dynamics of the receptor. Several studies have shown that the Janus kinase/signal transducer and activator of transcription (JaK/STAT) and early growth response 3 (Egr3) signaling pathways can alter GABA(A)R subunit expression after status epilepticus (SE). In this study we investigated changes in these pathways after experimental TBI in the rat using a lateral fluid percussion injury (FPI) model. Our results demonstrated changes in the expression of several GABA(A)R subunit levels after injury, including GABA(A)R α1 and α4 subunits. This change appears to be transcriptional, and there is an associated increase in the phosphorylation of STAT3, and an increase in the expression of Egr3 and inducible cAMP element repressor (ICER) after FPI. These findings suggest that the activation of the JaK/STAT and Egr3 pathways after TBI may regulate injury-related changes in GABA(A)R subunit expression.
authors: Neuroscience Program, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
authors: Daniel J
authors: DJ
authors: Raible
authors: Lauren C
authors: LC
authors: Frey
authors: Yasmin
authors: Y
authors: Cruz Del Angel
authors: Shelley J
authors: SJ
authors: Russek
authors: Amy R
authors: AR
authors: Brooks-Kayal
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism*; D004195:Disease Models, Animal; D051776:Early Growth Response Protein 3 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D053612:Janus Kinases / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C497370:Egr3 protein, rat; D011963:Receptors, GABA-A; D050791:STAT Transcription Factors; D051776:Early Growth Response Protein 3; D053612:Janus Kinases