Memory loss following a single generalized seizure is transient and reversible
Rajalaxmi Natarajan, PhD
A study conducted by Dr. Anne Anderson, epileptologist at Texas Children’s Hospital and an investigator at the Gordon and Mary Cain Pediatric Neurology Research Foundation Laboratories at the Jan and Dan Duncan Neurological Research Institute shows that structural alterations in neurons and the resulting memory deficits that arise after a single generalized seizure can be reversed by inhibiting the Phosphoinositide 3-kinase/Akt kinase/mechanistic target of rapamycin (i.e. PI3K/Akt/mTOR) signaling pathway. The study was published in eNeuro.
Seizures occur due to abnormal brain activity. The presence of two or more unprovoked seizures is defined as epilepsy. In addition to frequent seizures, severe chronic epilepsy is often characterized by cognitive defects, such as memory deficits.
Most nerve cells possess multiple branched dendrites that receive signals from neighboring neurons. Each dendrite has hundreds of small knob-like protrusion called ‘spines’ on its surface. Dendritic spines provide an anatomical substrate for memory storage and in particular, long-term memory is mediated by the growth of new or the enlargement of existing spines to reinforce a new neural pathway.
In this study, researchers found that a single self-limiting seizure induced by a chemoconvulsant, impairs learning and memory, hyper-activates the PI3K/Akt/mTOR signaling pathway and decreases the number of mature dendritic spines while increasing immature dendritic spines in rats. While these alterations were transient and resolved within a day of the seizure event, they affected short-and long-term memory of these animals.
More importantly, the team found that treating these animals with wortmannin, an inhibitor of PI3K, significantly improved their performance in short-and long-term memory-related behavioral tasks and reduced the number of immature dendritic spines, although it was not sufficient to prevent the loss of mature spines.
With this study, for the first time, we are being offered into glimpse into the molecular and structural alterations that occur in neurons after a single episode of generalized seizure. Researchers hope this will lay the groundwork for understanding and finding ways to prevent long-term memory loss after a seizure.