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Mouse Model Developed to Study Alzheimer’s

Wed, 11/09/2011 - 10:56am

Hirano bodies are tiny objects found in nerve cells of people suffering from conditions such as Alzheimer's, bovine spongiform encephalopathy or mad cow, and Lou Gehrig's diseases. Yet for decades, researchers weren't sure if these structures helped cause the conditions or appeared after onset of the disease and had some other role.

In research at the University of Georgia, a cellular biologist and his colleagues have found that Hirano bodies may play a protective role in the progression of neurodegenerative diseases such as Alzheimer's. And to find out why this may be happening, they have developed a transgenic mouse model that has Hirano bodies, which will open frontiers on how these poorly understood structures may be involved with these difficult-to-treat diseases.

"This work gives us a first view of the possible effects of Hirano bodies," says Marcus Fechheimer, Josiah Meigs Professor of cellular biology at UGA. "Now we know that Hirano bodies do not kill cells and are not toxic to mice. This new model will allow us to ask whether Hirano bodies have any effect on progression of disease in the brain."

While the research offers no cure for such diseases, it does create a new area of research into understanding how these diseases operate in the human body and why they are so difficult to treat.

Researchers discovered Hirano bodies decades ago but studying them in the lab proved so difficult that all the medical community could say was that the bodies were in some way associated with diseases such as Alzheimer's. It was clear that Hirano bodies are composed primarily of filaments of actin, a protein that participates in many important cellular processes. But no one understood their function.

In 2002, Fechheimer's lab reported a method of inducing the bodies to form. Interestingly, these "inclusions" also show up in autopsies of people suffering from diabetes, alcoholism, and cancer. Hirano bodies also are associated with normal aging. So understanding what they do when neurological processes go off the rails could add an important step in understanding how diseases progress.

In a companion paper to the mouse model research, Fechheimer and his co-authors discovered that Hirano bodies may act as a "corral" into which more damaging cellular molecules are "rounded up," thus actually promoting cell survival and possibly even slowing the impact of disease.
The idea that Hirano bodies may actually help protect cells from such disorders as Alzheimer's came as a surprise to the team, though much research remains to be done to make sure exactly what is happening.

"The new results show us that Hirano bodies reduce cell death in a model system in a culture dish," says Fechheimer. "Now we need to know if Hirano bodies have any harmful or protective effects on cells in the brain in a mouse and in human patients. We developed the new mouse model to begin to answer this question."

The model system will allow Fechheimer and his colleagues to study the impact of Hirano bodies in a living, mammalian system and to investigate the pathways for formation and degradation of the bodies. It will also allow them to test whether Hirano bodies promote or modulate the development of pathology or affect the deterioration of learning and memory that characterize both the human disease and the mouse models of these conditions.

The research was published in BMC Neuroscience.

Release Date: Nov. 7, 2011
Source: University of Georgia 

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