A new study describes for the first time a method of culturing important but poorly understood cell structures called Hirano bodies. The report by cellular biologists at the University of Georgia could shed light on numerous diseases in which Hirano bodies may play some role--including Alzheimer's disease, Lou Gehrig's Disease and cancer.
The research was published in the May issue of the Journal of Cell Science and was funded by the National Science Foundation (NSF) and the Alzheimer's Association.
Hirano bodies -- named for their discoverer -- have been known for several decades, and their presence in autopsy tissue of Alzheimer's patients has led to speculation that they may play a role in disease processes. Studying Hirano bodies, however, has been extremely difficult because they have been resistant to culturing in the laboratory.
The new study, led by cellular biologist Marcus Fechheimer, reports a novel way to create Hirano bodies in the lab, giving scientists their first tool to understand how the bodies may aid-or hinder--the progress of disease.
“This is a wonderful example of why it is so important for scientists to pursue very basic, fundamental, curiosity-driven studies in cell biology,” says Eve Barak, program director in NSF’s division of cellular and molecular biosciences. “Eventually such research will lead to something of great value to society.”
Scientists have for three decades found Hirano bodies in the post-mortem examination of brain tissue from patients with neurodegenerative diseases, diabetes, alcoholism and cancer.
Understanding just what Hirano bodies do remains murky at best. They may change cells to make them more vulnerable to disease, but it's currently just as likely that they help battle disease; nobody knows. That's why the new results are exciting and offer a key tool for investigations of these structures.
The team used an unlikely candidate for a model system for neuro-degenerative disease: the slime mold Dictyostelium. The discovery of Hirano bodies in Dictyostelium was an accidental offshoot of basic cell biology research that Fechheimer and his students pursued for more than a decade. The research team found at least five points of similarity between Dictyostelium Hirano bodies and those found from human autopsy samples.
Until now, Hirano bodies have been found by autopsy most often in the hippocampus region of the brain, though the bodies are not restricted to neurons. Still, the bodies appear to have some association with a wide range of diseases, including ataxic Creutzfeldt-Jakob disease, Pick's disease (both neurodegenerative disorders) and diabetes.
The presence of Hirano bodies in association with all these diseases has led scientists to speculate that they have some role in neurological deterioration--especially in diseases like Alzheimer's. Fechheimer and his colleagues, however, argue that their results support a broader interpretation. They propose that a range of conditions may generate signals that induce the formation of Hirano bodies.
So far, nobody knows if these bodies are doing good or bad things for cells. Some researchers had speculated that the bodies played a role in apoptosis or so-called "programmed cell death," in which cells signal for their own demise, often for the good of the entire organism. However, Fechheimer’s work shows that Hirano bodies are not necessarily linked to a stage in cell death. The new ability to create Hirano bodies in the lab will allow researchers to explore their mechanisms with greater understanding.
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