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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Dictyostelium cells (see left column)
containing Hirano bodies that contain
actin filaments (middle column) were stained
with a panel of antibodies to determine
the presence of other selected cytoskeletal
proteins (right column). Dictyostelium
Hirano bodies contain actin, cofilin (C),
myosin II (B), and alpha-actinin (D),
but not tubulin (A), ABP 120 (E), or EF
1-alpha (F).
Credit: Courtesy of Marcus Fechheimer,
Professor of Cellular Biology, University
of Georgia
Select image for larger version
(Size: 164KB)
A Hirano body in a Dictyostelium amoeba
is shown in panel A. Transverse and longitudinal
sections reveal the filament organization
in the Hirano bodies. The filaments are
approximately 10 nanometers (nm) in diameter,
and spaced at intervals of 20 nm within
rows.
Credit: Courtesy of Marcus Fechheimer,
Professor of Cellular Biology, University
of Georgia
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