Blader Continuing Study of Seizures Caused by Parasitic Infections

The research will be funded by a five-year, $2.7 million grant from the National Institute of Allergy and Infectious Diseases.

Blader’s prior research revealed that when Toxoplasma actively grows in the brain (a condition known as toxoplasmic encephalitis), it causes a massive reorganization of inhibitory synapses.

“We published a paper in 2015 showing that in mice infected with Toxoplasma, the enzyme that makes a neurotransmitter called gamma-aminobutyric acid (GABA) is misplaced, and this likely leads to a defect in the synthesis and function of GABA,” he says.

“The reason this is important is because GABA’s primary function is to regulate electrical activity in the brain,” Blader says. “So when GABA activity is reduced, the electrical signaling in the brain becomes dysregulated, which can result in the development of seizures.”

Indeed, the researchers found that mice suffering from toxoplasmic encephalitis developed seizures.

The researchers now aim to:

• define how the proteins are mislocalized
• determine the role of inflammatory cells in GABAergic protein mislocalization
• identify the parasite factors that affect GABAergic protein localization and onset of seizures

“We are focused on identifying the parasite factors that cause mislocalization of the GABA synthesizing protein, how this factor functions and what happens to other proteins that are associated with GABA neurotransmission,” Blader says.

T. gondii causes one of the most widespread infections, with more than one-third of the world’s population estimated to be affected.

Most people are asymptomatic because the parasite resides latently within the brain and other tissues.

However, individuals who are immunocompromised or are infected in utero face serious, life-threatening illness.

Besides its own medical importance, Blader says Toxoplasma is studied because it represents an ideal model system.

“It is a great model system because it can easily be grown in vitro, its genome is sequenced and it can be genetically manipulated,” he says.

The hope is that continued research will shed light on the mechanisms that are responsible for seizures and to use the resulting information to enhance patient outcomes.

“The long-term goal of this work is to determine how seizures develop in Toxoplasma-infected individuals and use this information to generate novel therapies to treat these patients and others suffering from infection-induced seizures,” Blader says.

The research project is being done in collaboration with Michael Fox, PhD, of the Virginia Tech Carilion Research Institute.