Seizures Affect Long-Term Memory in Animal Study

Inhibiting the pathway upstream of mTOR at the level of PI3K signaling, a locus of significant molecular crosstalk in this pathway, restored the seizure-induced learning and memory deficits.

PHILADELPHIA — Research in animals suggests that seizures may impact the signaling cascades necessary for long-term memory formation, and that inhibition of phosphoinositide 3-kinase (PI3K) signaling may restore seizure-induced memory deficits.

“Our findings indicate that in genetically normal animals, a single generalized convulsive seizure results in cognitive deficits and is associated with dysregulation of the PI3K-mTOR signaling pathway,” Angela N. Carter, PhD candidate at Baylor College of Medicine, Houston, told Neurology Advisor. “Currently, the focus is on targeting this pathway in genetic disorders of PI3K-mTOR signaling, such as tuberosclerosis, but based on our findings consideration should be given to a more broad application in epilepsy-associated cognitive dysfunction.”

In the study, which was presented at the 2015 American Epilepsy Society Annual Meeting in Philadelphia, Carter, principle investigator Anne E. Anderson, MD, and colleagues sought to better understand how a single generalized tonic-clonic seizure affected learning and memory, and whether hyperactivation of the PI3K and mechanistic target of rapamycin (mTOR) cascades contributed to seizure-induced learning and memory deficits.

The study included rats that were given either saline (control) or the chemoconvulsant pentylenetetrazole (PTZ) to induce a generalized seizure. Researchers collected brain tissue at hours 1, 3, and 24 and examined the tissue to establish how seizures impact PI3K and mTOR activation.

“We hypothesized that hyperactivation of the PI3K and mTOR cascade contributes to learning and memory deficits that are associated with a single generalized seizure,” Carter said. “Previous studies emphasized the role of hyperactive signaling of the mTOR pathway in epilepsy-associated learning and memory disorders, but this pathway had not been investigated for a role in these deficits following a single generalized seizure.”