Glial response to neuronal activity: GFAP-mRNA and protein levels are transiently increased in the hippocampus after seizures.
We have recently demonstrated that electrically induced seizures lead to dramatic increases in mRNA for GFAP in areas in which seizures occur. The present study evaluates the time course of the changes in the GFAP-mRNA levels after seizures and the relationship between these changes and GFAP protein levels to understand the role of neuronal activity in regulating glial gene expression. GFA protein and mRNA levels were measured in hippocampi from rats in which seizures were induced by: (1) 50-Hz stimulus trains delivered 12 times over the course of 1 day via indwelling electrodes implanted chronically in the CA3 region of the hippocampus; and (2) intraperitoneal injections of pentylenetetrazol. In the case of the electrically induced seizures, we also compared the glial response in animals that had never experienced a seizure with the response in animals that previously had been kindled but had not experienced a seizure for 30 days. Electrically induced seizures led to rapid transient increases in GFAP-mRNA levels in the hippocampus ipsi- and contralateral to the stimulation. GFAP-mRNA increased about five-fold 1 day after the end of seizure activity and returned to near-control levels by 4 days. There were no detectable increases in GFA protein at 1 day but by 2 days GFA protein levels had increased about two-fold. GFA protein levels remained elevated until 4 days poststimulation and then began to decrease. The responses were similar when seizures were induced in kindled animals, except that the GFAP protein levels remained elevated for somewhat longer.(ABSTRACT TRUNCATED AT 250 WORDS)
Torre
E R
ER
Department of Neuroscience, University of Virginia Health Sciences Center, Charlottesville 22908.
Lothman
E
E
Steward
O
O
D000818:Animals; D015153:Blotting, Western; D004567:Electrodes, Implanted; D004597:Electroshock; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis* / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism*; D007696:Kindling, Neurologic / Q000502:physiology; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D010433:Pentylenetetrazole; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D015347:RNA Probes; D012333:RNA, Messenger; D010433:Pentylenetetrazole