PT  - JOURNAL ARTICLE
AU  - Carter, Angela N.
AU  - Born, Heather A.
AU  - Levine, Amber T.
AU  - Dao, An T.
AU  - Zhao, Amanda J.
AU  - Lee, Wai L.
AU  - Anderson, Anne E.
TI  - Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats
AID  - 10.1523/ENEURO.0354-16.2017
DP  - 2017 May 01
TA  - eneuro
PG  - ENEURO.0354-16.2017
VI  - 4
IP  - 3
4099  - http://www.eneuro.org/content/4/3/ENEURO.0354-16.2017.short
4100  - http://www.eneuro.org/content/4/3/ENEURO.0354-16.2017.full
SO  - eNeuro2017 May 01; 4
AB  - 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 (Wort), 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.