Regulation of GABA transporter mRNA and protein after photothrombotic infarct in rat brain.
Animal models of focal ischemic infarcts reveal an impaired GABAergic (gamma-aminobutyric acid) neurotransmission. GABA, the main inhibitory neurotransmitter, is primarily taken up by specific sodium-dependent transporters. As these transporters play a crucial role in maintaining levels of GABA concentration, they may be functionally involved in ischemic processes. We investigated whether the mRNA and protein expression of GAT-1, the dominant neuronal GABA transporter, is altered after cortical infarct induced by photothrombosis in Wistar rats. In situ hybridization was performed to analyze GAT-1 mRNA-positive cells in cortical brain regions and the hippocampus. The lesion dramatically raised the number of GABA transporter mRNA-expressing cells in all investigated cortical regions. Double-labeling studies with a general neuronal marker and a marker for astrocytes revealed that cells expressing GAT-1 mRNA after photothrombosis are neurons. The mRNA expression pattern of all hippocampal subfields remained unchanged. In contrast, cortical GAT-1 protein density was only slightly affected and surprisingly in the opposite way. In the primary and secondary somatosensory cortex, density values were significantly reduced. Immunoreactivity was not altered in all investigated hippocampal areas. We found a marked discordance between the increased number of cells expressing GAT-1 mRNA in the cortex and the reduced tissue GAT-1 protein content. Focal brain ischemia obviously triggers mechanisms that interfere with GAT-1 transcriptional regulation and protein synthesis or turnover.
Frahm
Christiane
C
Department of Neurology, Friedrich-Schiller-University, 07745 Jena, Germany. christiane.frahm@med.uni-jena.de
Haupt
Corinna
C
Weinandy
Franziska
F
Siegel
Gabriele
G
Bruehl
Claus
C
Witte
Otto W
OW
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002544:Cerebral Infarction / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D050485:GABA Plasma Membrane Transport Proteins; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D050485:GABA Plasma Membrane Transport Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C493415:Slc6a1 protein, rat