%0 Journal Article %A Angela N. Carter %A Heather A. Born %A Amber T. Levine %A An T. Dao %A Amanda J. Zhao %A Wai Ling Lee %A Anne E. Anderson %T WORTMANNIN ATTENUATES SEIZURE-INDUCED HYPERACTIVE PI3K-Akt-mTOR SIGNALING, IMPAIRED MEMORY, and SPINE DYSMORPHOLOGY iN RATS %D 2017 %R 10.1523/ENEURO.0354-16.2017 %J eneuro %P ENEURO.0354-16.2017 %X Numerous studies have shown epilepsy-associated cognitive deficits, but less is known about the effects of one single generalized seizure. Recent studies demonstrate that a single, self-limited seizure can result in memory deficits and induces hyperactive phosphoinositide 3-kinase/Akt (protein kinase B)/mechanistic target of rapamycin (PI3K/Akt/mTOR) signaling. However, the effect of a single seizure on subcellular structures such as dendritic spines and the role of aberrant PI3K/Akt/mTOR signaling in these seizure-induced changes are unclear. Using the pentylenetetrazole (PTZ) model, we induced a single generalized seizure in rats and: 1) further characterized short and long-term hippocampal and amygdala-dependent memory deficits, 2) evaluated whether there are changes in dendritic spines, and 3) determined whether inhibiting hyperactive PI3K/Akt/mTOR signaling rescued these alterations. Using the PI3K inhibitor wortmannin, we partially rescued short and long-term memory deficits, and altered spine morphology. These studies provide evidence that pathological PI3K/Akt/mTOR signaling plays a role in seizure-induced memory deficits as well as aberrant spine morphology.Significance Statement Epilepsy-associated memory deficits were originally thought to only arise in chronic epilepsy. However, the current studies demonstrate that a single generalized seizure can result not only short, but also long-term memory deficits. Furthermore, the mechanisms of how a single generalized seizure impairs memory are not well known. We find that the seizure-induced memory impairments are transient and are linked, in part, to dysregulated signaling of a memory related cascade (PI3K/Akt/mTOR) and possibly also disruptions in spine morphology, both of which are crucial for memory formation. Our studies are clinically relevant as we demonstrate that a single generalized seizure can profoundly impair memory, particularly long-term memory, despite the transient nature of the molecular and structural perturbations. %U https://www.eneuro.org/content/eneuro/early/2017/05/05/ENEURO.0354-16.2017.full.pdf