Abstract
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.
- learning and memory
- seizures
- phosphosinositide-3 kinase
- mechanistic target of rapamycin
- mTOR inhibitor
- wortmannin
- spine morphology
- protein kinase B/Akt
Footnotes
The authors declare no competing financial interests.
This work was supported by the National Institutes of Health/National Institute for Neurologic Disorders and Stroke (NIH/NINDS) R01 NS081053 (to A.E.A.) as well as by the NIH/NINDS Predoctoral Fellowship F31 NS080566 (to A.N.C.).
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