title: Expression of GABA A receptor alpha1 subunit mRNA and protein in rat neocortex following photothrombotic infarction.
abstract: Photothrombotic infarcts of the neocortex result in structural and functional alterations of cortical networks, including decreased GABAergic inhibition, and can generate epileptic seizures within 1 month of lesioning. In our study, we assessed the involvement and potential changes of cortical GABA A receptor (GABA AR) alpha1 subunits at 1, 3, 7, and 30 days after photothrombosis. Quantitative competitive reverse transcription-polymerase chain reaction (cRT-PCR) and semi-quantitative Western blot analysis were used to investigate GABA AR alpha1 subunit mRNA and protein levels in proximal and distal regions of perilesional cortex and in homotopic areas of young adult Sprague-Dawley rats. GABA AR alpha1 subunit mRNA levels were decreased ipsilateral and contralateral to the infarct at 7 days, but were increased bilaterally at 30 days. GABA AR alpha1 subunit protein levels revealed no significant change in neocortical areas of both hemispheres of lesioned animals compared with protein levels of sham-operated controls at 1, 3, 7, and 30 days. At 30 days, GABA AR alpha1 subunit protein expression was significantly increased in lesioned animals within proximal and distal regions of perilesional cortex compared with distal neocortical areas contralaterally (Student's t-test, p<0.05). Short- and long-term alterations of mRNA and protein levels of the GABA AR alpha1 subunit ipsilateral and contralateral to the lesion may influence alterations in cell surface receptor subtype expression and GABA AR function following ischemic infarction and may be associated with formative mechanisms of poststroke epileptogenesis.
authors.affiliation: Department of Neurology, Center for Neuroscience Research, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA, USA.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Kharlamov
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Downey
authors.forename: Peter I
authors.initials: PI
authors.lastname: Jukkola
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Grayson
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Kelly
mesh_terms: D000818:Animals; D002544:Cerebral Infarction / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007839:Functional Laterality / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D020767:Intracranial Thrombosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D007834:Lasers; D008028:Light Coagulation; D019579:Neocortex / Q000098:blood supply / Q000378:metabolism*; D009433:Neural Inhibition / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012395:Rose Bengal; D009435:Synaptic Transmission / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C546242:Gabra1 protein, rat; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D012395:Rose Bengal; D005680:gamma-Aminobutyric Acid