Pharmacological inhibition of the mammalian target of rapamycin pathway suppresses acquired epilepsy.
Inhibition of mTOR by rapamycin has been shown to suppress seizures in TSC/PTEN genetic models. Rapamycin, when applied immediately before or after a neurological insult, also prevents the development of spontaneous recurrent seizures (epileptogenesis) in an acquired model. In the present study, we examined the mTOR pathway in rats that had already developed chronic spontaneous seizures in a pilocarpine model. We found that mTOR is aberrantly activated in brain tissues from rats with chronic seizures. Furthermore, inhibition of mTOR by rapamycin treatment significantly reduces seizure activity. Finally, mTOR inhibition also significantly suppresses mossy fiber sprouting. Our findings suggest the possibility for a much broader window for intervention for some acquired epilepsies by targeting the mTOR pathway.
Huang
Xiaoxing
X
Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA.
Zhang
Hailong
H
Yang
Jun
J
Wu
Jingfan
J
McMahon
John
J
Lin
Yufan
Y
Cao
Zhonglian
Z
Gruenthal
Michael
M
Huang
Yunfei
Y
D000818:Animals; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology*
D003292:Convulsants; D010862:Pilocarpine; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus