title: Alterations of GABA(A) and glutamate receptor subunits and heat shock protein in rat hippocampus following traumatic brain injury and in posttraumatic epilepsy.
abstract: Traumatic brain injury (TBI) can result in the development of posttraumatic epilepsy (PTE). Recently, we reported differential alterations in tonic and phasic GABA(A) receptor (GABA(A)R) currents in hippocampal dentate granule cells 90 days after controlled cortical impact (CCI) (Mtchedlishvili et al., 2010). In the present study, we investigated long-term changes in the protein expression of GABA(A)R α1, α4, γ2, and δ subunits, NMDA (NR2B) and AMPA (GluR1) receptor subunits, and heat shock proteins (HSP70 and HSP90) in the hippocampus of Sprague-Dawley rats evaluated by Western blotting in controls, CCI-injured animals without PTE (CCI group), and CCI-injured animals with PTE (PTE group). No differences were found among all three groups for α1 and α4 subunits. Significant reduction of γ2 protein was observed in the PTE group compared to control. CCI caused a 194% and 127% increase of δ protein in the CCI group compared to control (p<0.0001), and PTE (p<0.0001) groups, respectively. NR2B protein was increased in CCI and PTE groups compared to control (p=0.0001, and p=0.011, respectively). GluR1 protein was significantly decreased in CCI and PTE groups compared to control (p=0.003, and p=0.001, respectively), and in the PTE group compared to the CCI group (p=0.036). HSP70 was increased in CCI and PTE groups compared to control (p=0.014, and p=0.005, respectively); no changes were found in HSP90 expression. These results provide for the first time evidence of long-term alterations of GABA(A) and glutamate receptor subunits and a HSP following CCI.
authors: Center for Neuroscience Research, Allegheny-Singer Research Institute, Allegheny General Hospital, 320 East North Avenue, Pittsburgh, PA 15212-4772, United States. ekharlam@wpahs.org
authors: Elena A
authors: EA
authors: Kharlamov
authors: Eka
authors: E
authors: Lepsveridze
authors: Maia
authors: M
authors: Meparishvili
authors: Revaz O
authors: RO
authors: Solomonia
authors: Bo
authors: B
authors: Lu
authors: Eric R
authors: ER
authors: Miller
authors: Kevin M
authors: KM
authors: Kelly
authors: Zakaria
authors: Z
authors: Mtchedlishvili
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism*; D004834:Epilepsy, Post-Traumatic / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006624:Hippocampus / Q000293:injuries / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis* / Q000235:genetics; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor