The cure for Alzheimer’s may be found inside a mouse’s brain.

A group of students and professors from the University are attempting to understand the function of Hirano bodies in the brain to learn more about their associations with diseases like Alzhiemer’s. Marcus Fechheimer, Josiah Meigs Professor of cellular biology at the University, has been doing research at UGA for a 27-year span — however he and his students initially researched slime molds, not the medical analysis of Hirano bodies.

It was not until the discovery that Hirano bodies can be studied directly from slime molds that the group decided they would focus their research on the Hirano bodies.

“It was serendipitous,” Fechheimer said. “We now had a chance to do something with a more medical focus. We thought that we had a chance to work on something no one else in the world was working on, so we would try to do it.”

Hirano bodies are enriched inclusions and are primarily composed of a protein called actin. They are observed usually in autopsy examinations in association with a variety of conditions including Alzheimer’s disease, but because they are usually observed at autopsy there is no good way to investigate their contribution to the disease process they are associated with.

“The two major pathologies that people know about Alzheimer’s disease are plaques and tangles.” Said Connor Sweetnam, sophomore cell biology major from Suwanee, Georgia. “That’s what you often see after the death of someone with the disease, but Hirano bodies are something we haven’t been able to learn as much about.”

People do not know if Hirano bodies make the disease worse, are protective to the body, or have no effect on the disease at all. Fechheimer partnered up with Dr. Ruth Furukawa, who is an associate research scientist, and together they work with undergraduate and graduate students like Sweetnam to learn the secrets of Hirano bodies.

“Working with students is something I really enjoy at the university. I teach all levels at the school, but I really love working with undergrad and graduate students in the laboratory,” Fechheimer said.

Fechheimer allows his students to take leading roles in the research they do. Years ago, when the group first began looking at Hirano bodies in the slime mold, one of Fechheimer’s students named Sangdeuk Ha first suggested studying the Hirano bodies in the brains of mice.

“Dr. Ha wanted to create a model that would allow us to study the function of Hirano bodies,” Fechheimer said. “We had studied the Hirano bodies in slime mold at first and then watched the effects in culture dishes.  Dr. Ha found that the Hirano bodies would even protect cells from dying in culture dishes, so he thought we should be able to study this in the context of a brain.”

Ha and Fechheimer used a recombinant DNA approach to take the transgene that was used to induce the Hirano bodies and  targeted it into an embryonic stem cell. They labeled it with green fluorescent protein so it could be seen and then flanked it with DNA so the expression of the gene (turning it on) could be manipulated.

Hirano bodies were then put into one lab mouse. Then, the mouse was crossed to another mouse carrying a gene that recognized the flanking DNA sequences, and the gene was expressed and made in the brain. After six months time the Hirano bodies to began to show in the second mouse. The researchers have noted the mice appeared healthy, were fertile, and the part of the brain responsible for learning and memory looked normal.

Yearning for deeper meanings to their discovery, Fechheimer and his many students involved in the research turned to Dr. John Wagner from the College of Veterinary medicine at UGA for help. Together, Wagner’s students and Fechheiemer’s students used electrophysiology to study the signals between different neurons in the hippocampus. Electrophysiology entails making slices of the hippocampus and impaling it with microelectrodes.

Because the hippocampus deals with memory and learning abilities that are affected in Alzheimer’s disease, the researchers are hoping to find what Hirano bodies may do to enhance or deter the disease progression.

“Hirano bodies are in several diseases, but we focus on Alzheimer’s because there are so many people with this terrible condition and other researchers have already created mice that do model Alzheimer’s,” Fechheimer said.  “These are mice that develop the same inclusions in their brain that people do when they have Alzheimer’s.”

The researchers aim to study four types of mice after crossing their mice with mice that have Alzheimer’s—regular mice, Alzheimer’s mice, mice with Hirano bodies, and Alzheimer’s mice with Hirano bodies. The focus will be on deposits that form in the brain, their learning and memory by means of a mouse maze, and signals between the neurons.

“It’s most important that  through electrophysiology we found differences in the way that the neurons were communicating in the brains of Hirano body mice were different than the control mice,” Wagner said. “That showed there was something different about the Hirano body mice that Dr. Fechheimer and his students generated.”

Fechheimer said basic exploration can lead to tremendous insights in medical research.

“We did not set out initially to do something that was so targeted in a medical way, but because we discovered something it gave us a chance to do something related to medicine and disease.”