Study Finds Mossy Cell Degeneration Contributes to Seizure Disorders
Convulsive seizures in temporal lobe epilepsy (TLE) are serious and can be debilitating and life-threatening. A new study has found that the loss of a group of cells in the brain can contribute no only to seizures in TLE, but also to memory problems that accompany the seizures in the people with the disorder.
These cells, called mossy cells for the appearance of moss-like protrusions that cover their cell surface, are found in the hippocampus, a brain area that is known to play key roles in memory. Numerous studies have reported that TLE is associated with the loss of mossy cells. A team from Stanford University modified a cellular system to switch mossy cells on, and off, in mice that are used as a research model of TLE.
The important part of the study by the group, led by Dr. Ivan Soltesz, was that the switch they used could prevent local seizure activity from developing into full-blown generalized convulsive seizures. The absence of functioning mossy cells increased the likelihood of the occurrence of full-blown seizures. The mice the Stanford investigators used were bioengineered so that their mossy cells responded to pulses of light, conveyed to those cells via an implanted optical fiber. Blue light caused mossy cells to fire, while amber light caused them to resist firing. So, by flipping a laser switch, the scientists could activate or inhibit the mice’s mossy cells at will.
“This was the first time we were able to show specifically that mossy cell activity can control convulsive seizures,” said Anh Bui, an M.D., Ph.D. student at the University of California-Irvine, and first author of the paper. “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.”
The study also examined the effects of mossy cell activity on mouse memory and found that mossy cells contribute to spatial memory, but not to the ability of the mice to recognize objects.
While these findings suggest that a decrease in mossy cells may lead to convulsive seizures as well as memory deficits, the study did not address the root causes of the loss of mossy cells as part of their experimental design.
Known causes of mossy cell death include exposure to methamphetamines, alcohol, pilocarpine (a medicine used for glaucoma), zinc deficiency, traumatic brain injury, and exposures to neurotoxic metals. Aluminum in particular is known to cause inflammation of the hippocampus and other parts of the brain, and injected aluminum hydroxide, a salt used as an adjuvant in vaccines, can be used to induce aquired epilepsy in mice (Avanzini et al., 2016).
One study found that berberine, a plant compound, could normalize mossy cell growth. [See more studies here].
Avanzini, G. et al., 2016. Animal Models of Acquired Epilepsies and Status Epilepticus. Neupsy Key, 2016. [Web Link]
More info: Bui AD et al. Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial memory. Science. February 16, 2018.
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