Spreading depression and reverberatory seizures induce the upregulation of mRNA for glial fibrillary acidic protein.
The present study evaluates the relative roles of seizure activity and spreading depression in upregulating glial fibrillary acidic protein (GFAP) mRNA expression. Stimulating electrodes were placed bilaterally in the angular bundle, and recording electrodes were placed bilaterally in the dentate gyrus of adult rats. Intense electrographic seizures were induced by delivering stimulus trains through one stimulating electrode. In some cases, spreading depression accompanied the seizures, while in other cases, the seizures occurred in the absence of spreading depression. Animals were killed 24 h following the last stimulus train, and the forebrains were prepared for quantitative in situ hybridization. Seizure activity and spreading depression led to significant increases in GFAP mRNA levels in the hippocampal formation. Seizure activity alone (without spreading depression) induced a 4-fold increase in GFAP mRNA levels in the hilus and molecular layer of the dentate gyrus and in stratum lacunosum-moleculare of the hippocampus. When seizure activity was accompanied by spreading depression, there was a 10-fold increase in GFAP mRNA levels in these same regions. Regional differences within the hippocampal formation in glial cell response were evident. While GFAP mRNA levels in stratum lacunosum-moleculare of the hippocampus were upregulated by seizure activity and spreading depression, levels in hippocampal stratum radiatum of the hippocampus remained unchanged. The results suggest that abnormal neuronal activity can influence glial cell gene expression and that spreading depression is a stronger signal than seizure activity in upregulating GFAP mRNA levels.
Bonthius
D J
DJ
Department of Neuroscience, University of Virginia Health Sciences Center, Charlottesville 22908.
Stringer
J L
JL
Lothman
E W
EW
Steward
O
O
D000818:Animals; D013181:Cortical Spreading Depression / Q000235:genetics*; D004558:Electric Stimulation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006624:Hippocampus / Q000503:physiopathology; D017403:In Situ Hybridization; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000235:genetics*
D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger