Prolonged infusion of cycloheximide does not block mossy fiber sprouting in a model of temporal lobe epilepsy.
OBJECTIVE
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.
Toyoda
Izumi
I
School of Veterinary Medicine, University of California-Davis, Davis, CA, U.S.A.
Buckmaster
Paul S
PS
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects* / Q000503:physiopathology; D009473:Neuronal Plasticity; D010862:Pilocarpine; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D011500:Protein Synthesis Inhibitors; D010862:Pilocarpine; D003513:Cycloheximide