Researchers find link between mossy cells and epilepsy

Loss of mossy cells may contribute to both the convulsive seizures suffered by patients with temporal lobe epilepsy (TLE) and their frequent memory difficulties, according to researchers of a recent study published in Science.

“The role of mossy cells in epilepsy has been debated for decades. This study reveals how critical these cells are in the disease, and the findings suggest that preventing loss of mossy cells or finding ways to activate them may be potential therapeutic targets,” said Vicky Whittemore, PhD, National Institute of Neurological Disorders and Stroke (NINDS) program director.

Found in the hippocampus, mossy cells are named for the moss-like protrusions that cover their surfaces.

In adults, TLE is the most common form of epilepsy—patients can have spontaneous seizures and are at an increased risk of developing serious cognitive impairment.

Researchers led by senior author Ivan Soltesz, PhD, professor of neurosurgery and neurosciences, Stanford University, Palo Alto, CA, found that they could turn mossy cells ”on” and ”off” to assess what effects they had in a murine model of epilepsy.

“This study would not have been possible without the rapid advancement of technology, thanks in part to the BRAIN Initiative, which has encouraged scientists to develop innovative instruments and new ways to look at the brain,” said Dr. Soltesz. “It’s remarkable that we can manipulate specific brain cells in the hippocampus of a mouse. Using 21st century tools brings us closer than ever to unlocking the mysteries behind this debilitating disease.”

Using electroencephalography scans, Dr. Soltesz and colleagues could detect focal seizures, which can result in symptoms such as twitching and a strange taste or smell. Focal seizures in patients with TLE can become generalized, spreading through the brain and causing convulsions and loss of consciousness.

The researchers were able to detect focal seizures in murine models and found that turning ”on” the mossy cells prevented the focal seizures from becoming generalized and resulting in convulsive seizures. When they turned the mossy cells “off,” however, convulsive seizures were more likely to occur. Although the mossy cells did not have a significant effect on the occurrence of focal seizures, this evidence of their link to convulsive seizures is exciting.

“This was the first time we were able to show specifically that mossy cell activity can control convulsive seizures,” said lead author Anh Bui, an MD, PhD student, University of California-Irvine, Irvine, CA. “These mice were missing most of their mossy cells, yet we were able to see effects just by manipulating the small number of surviving cells.” 

Dr. Soltesz, Bui, and fellow researchers then looked at the effects of mossy cells on two types of memory: object recognition and spatial memory. Patients with TLE often experience cognitive changes and problems with long-term memory.

They placed the mice into a chamber with two identical items. To test the mice’s object recognition, researchers replaced one of the items the next day with a different item. To test for spatial memory, they moved one of the items to a different location.

The spatial memory task was problematic for the mice with epilepsy, but their object recognition was not affected.

Further, in healthy mice in which mossy cells were turned “off,” problems with spatial memory began to occur. This suggests that a decrease in mossy cells may lead to memory deficits and to convulsive seizures.

More research on mossy cells is necessary to understand their role in seizure progression and early disease, concluded Dr. Soltesz and colleagues.

This study was funded by the NINDS of the National Institutes of Health.