Induction of cortical spreading depression with potassium chloride upregulates levels of messenger RNA for glial fibrillary acidic protein in cortex and hippocampus: inhibition by MK-801.
The present study evaluates the time course and spatial extent of changes in GFAP mRNA expression following the induction of spreading depression. Spreading depression was elicited by applying filterpaper pledgets soaked in KCl (3 M) to exposed parietal cortex for ten minutes. Animals were killed 1.5, 3, 6, 12, 24, 48, 96 and 192 h post-KCl application, and the forebrains were prepared for quantitative in situ hybridization. The KCl treatment led to a many-fold increase in GFAP mRNA content in the ipsilateral hippocampus and neocortex and, to a lesser extent, in the contralateral hippocampus, but did not affect GFAP mRNA levels in the contralateral cortex or in the thalamus. The time course of increased expression of GFAP mRNA in the hippocampus differed markedly from that of the cortex. In the hippocampus, GFAP mRNA levels rose rapidly to a maximum at 24 h post-exposure, then fell rapidly. In the cortex, levels rose more slowly and did not reach a maximum until 4 days post-exposure. Analysis of GFAP mRNA levels by dot blot hybridization using samples from a separate set of animals killed at one and 4 days following the KCl exposure confirmed both the upregulation in GFAP mRNA levels and the regional time course differences. Intraperitoneal injection of MK-801, a non-competitive NMDA antagonist which prevents spreading depression, blocked the upregulation of GFAP mRNA in both the hippocampus and the cortex, as demonstrated by both in situ and dot blot hybridization. The results suggest that the physiological changes accompanying spreading depression have a powerful influence on glial cell gene expression.
Bonthius
D J
DJ
Department of Neuroscience, University of Virginia Health Sciences Center, Charlottesville 22908.
Steward
O
O
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D013181:Cortical Spreading Depression / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D006624:Hippocampus / Q000187:drug effects*; D015151:Immunoblotting; D017403:In Situ Hybridization; D008297:Male; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D011189:Potassium Chloride; D016291:Dizocilpine Maleate