The role of postlesion seizures and spreading depression in the upregulation of glial fibrillary acidic protein mRNA after entorhinal cortex lesions.
Unilateral lesions of the entorhinal cortex have been shown to lead to dramatic increases in GFAP mRNA levels in denervated zones in the hippocampus and dentate gyrus and sometimes (but not always) in nondenervated zones in the contralateral hippocampus and dentate gyrus. The variable distribution of the increases in GFAP mRNA expression suggests that the events which trigger changes in GFAP mRNA levels occur to a variable extent in individual animals. The companion paper characterizes two candidate triggering events: spreading depression (SD) that occurs to a variable extent at the time of the lesion and recurrent seizures that occur during the early postlesion interval. The goal of the present study was to evaluate whether individual differences in the extent or spatial distribution of lesion-induced increases in GFAP mRNA are related to the occurrence of either SD or seizures. We quantified the increases in GFAP mRNA levels in individual animals that had been monitored physiologically to define the incidence of SD and postlesion seizures. The results revealed that the quantitative extent of the increases in GFAP mRNA in denervated zones and was not related to either SD or postlesion seizures. The increases in GFAP mRNA in nondenervated zones also were not related to episodes of spreading depression that occurred at the time of lesion production but were related to the spontaneous seizures that developed during the first 24 h postlesion after the animals had recovered from the surgical anesthesia. Taken together, these data indicate that physiological events that occur during the early postlesion interval can play an important role in determining the pattern and extent of altered cellular gene expression in response to an injury.
Kelley
M S
MS
Department of Neuroscience, University of Virginia, Charlottesville 22908, USA.
Steward
O
O
D000818:Animals; D013181:Cortical Spreading Depression / Q000502:physiology*; D003714:Denervation; D018891:Dentate Gyrus / Q000503:physiopathology; D018728:Entorhinal Cortex / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D017403:In Situ Hybridization; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology*
D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger