Researchers have found that low levels of a protein associated with bipolar disorder also triggers epileptic seizures in mice — a discovery that may explain some of the similarities between the two conditions.
The protein, called ANK3, controls the balance between inhibitory and excitatory brain signals. When it’s lacking, it leads to the excessive nerve signaling seen in both epilepsy and bipolar disorder.
Researchers behind the study, “Ankyrin-G isoform imbalance and interneuronopathy link epilepsy and bipolar disorder,” hope the insights will lead to research for better treatments for both epilepsy and bipolar disorder. The work was published in the journal Molecular Psychiatry.
“We became very interested in a gene called ankyrin 3, or ANK3, a decade ago when we discovered it coded for a partner of two other genes that are mutated in some people with epilepsy,” Dr. Edward C. Cooper, associate professor of neurology, molecular and human genetics, and neuroscience at Baylor College of Medicine in Texas, said in a press release.
Large genetic studies in patients with bipolar disorder revealed that ANK3 was also connected to the psychiatric condition.
“Although there are important differences, we noted similarities between bipolar disorder and epilepsy: both cycle, both are risk factors for the other, and both are currently treated using many of the same drugs,” Cooper said.
But although researchers noticed the similarities, they could not explain them. The ANK3 gene can give rise to several alternative proteins, and researchers didn’t know what the variant linked to bipolar disorder did in the brain.
To better understand these connections, the research team started studying a mouse model of bipolar disorder. The team discovered that brain cells that sent inhibitory signals — decreasing the output of other cells — contained a different version of the protein than excitatory neurons, which increase the output of their target cells.
The version of the protein that is low in bipolar patients was selectively lost from the inhibitory neurons, making them lose their normal signaling patterns. Since excitatory nerve cells were unaffected, the result was an excessive activating signaling.
Mice that lacked the “inhibitory” version of ANK3 did not only develop behavior similar to that seen in bipolar patients, they also had severe seizures and an increased risk of sudden death.
“This showed us that imbalance in ANK3 function can result not only in excessive circuit sensitivity and output leading to bipolar disorder, but also severe epilepsy,” Cooper said.