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Prolonged Infusion of Cycloheximide Does Not Block Mossy Fiber Sprouting in a Model of Temporal Lobe Epilepsy
Author(s) -
Toyoda Izumi,
Buckmaster Paul S.
Publication year - 2005
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2005.04605.x
Subject(s) - mossy fiber (hippocampus) , sprouting , temporal lobe , epilepsy , neuroscience , cycloheximide , medicine , clinical neurology , psychology , biology , hippocampal formation , dentate gyrus , botany , protein biosynthesis , microbiology and biotechnology
Summary: Purpose: The role of protein synthesis in mossy fiber sprouting is unclear. Conflicting reports exist on whether a single dose of the protein synthesis–blocker cycloheximide administered around the time of an epileptogenic injury can block the eventual development of mossy fiber sprouting. Methods: In rats, osmotic minipumps and cannulae were implanted to deliver 8 mg/ml cycloheximide to one dentate gyrus and vehicle to the other. This method has been used to block protein synthesis in the infused region for up to 5 days with minimal neurotoxic effects (Taha and Stryker, Neuron 2002;34:425–36). After 2 days of infusion, rats were treated with pilocarpine to induce status epilepticus. Pumps were removed 3 days later. Thirty days after pilocarpine treatment, rats were perfused, and hippocampal sections were processed for Timm staining. Results: Timm staining revealed aberrant mossy fiber sprouting in the inner molecular layer regardless of whether hippocampi were treated with cycloheximide or vehicle. Cycloheximide‐treated hippocampi displayed more aberrant Timm staining and more tissue damage around the infusion site than did vehicle‐treated hippocampi. Conclusions: Prolonged infusion of cycloheximide, spanning the period of pilocarpine treatment, did not block mossy fiber sprouting. This finding suggests that protein‐dependent mechanisms around the time of an epileptogenic injury are not necessary for the eventual development of synaptic reorganization.