Alzheimer's, Dementia & Mental Health
Death of Nerve Cells Caused by Alzheimer’s is
Observed in Live Organism for First Time
Zebrafish used by German researchers for
breakthrough that may advance search for drugs that can stop this
extensive cell death
April 14, 2009 – The death of nerve cells that lead
to severe dementia for patients with Alzheimer’s disease has, for the
first time, been observed in a living organism – a zebrafish. Until
now, it has only been possible to investigate the nerve cell devastation
in post mortem animal models, and by using complicated methods.
Researchers at the German Center for
Neurodegenerative Disease at Ludwig-Maximilians-Universitaet (LMU)
Muenchen, headed by Professor Christian Haass, have now successfully
observed this demise of nerve cells by life imaging.
The scientists inserted a gene into zebrafish
that
leads to a severe form of Alzheimer's in humans. The translucent larvae
thereupon developed characteristic symptoms such as the death of neurons
– the first directly observable instance in a living organism.
"Our discovery now allows us to perform a targeted
search for drugs that can stop the extensive cell death, and thereby
stop dementia in patients," says Haass.
"The first findings have already shown that we can
in principle use drugs to block at least some of the disease-related
processes in the zebrafish
."
The report on the study was posted online today by
the Journal of Clinical Investigation.
There are an estimated 12 to 18 million AD patients
around the world. This trend is growing rapidly with the longer life
expectancy of people in western society.
The search for AD therapies is highly sought, since
neuronal cell death in the brains of Alzheimer's patients can still not
be defeated. Moreover, the death of neurons can only be truly confirmed
after the death of the patient. Even in animal models, the destruction
of nerve cells has only been observable to a very limited extent and
with great difficulty, the researchers say.
Professor Christian Haass and his two colleagues
Dr. Bettina Schmidt and Dominik Paquet of the Deutsche Zentrum für
Neurodegenerative Erkrankungen, DZNE (German Center for
Neurodegenerative Disease) at LMU Muenchen and the cluster of excellence
Center for Integrated Protein Science (CIPSM) report they have now
inserted a gene responsible for a severe form of Alzheimer's in people
into zebrafish
, with great success. The animals exhibited the
characteristic symptoms, such as deposits in nerve cells and the
selective loss of neurons.
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About
Zebrafish
The zebrafish (Danio rerio)
is a small tropical fresh-water fish which lives in rivers of
northern India, northern Pakistan, Nepal, and Bhutan in South
Asia. Due to its small size and ease of culture, the zebrafish
has become a favorite model organism for biologists studying
embryonic development.
The development of the zebrafish is very similar to the
embryogenesis in higher vertebrates, including humans. But
unlike mammals, zebrafish develop from a fertilized egg to an
adult outside the female in a transparent egg. This makes it
possible to observe developing embryos in their "natural
environment". Moreover, the embryos themselves are transparent
during the first few days of their lives. This allows
researchers to observe the formation of internal organs "live"
inside the living organism.
>>
More at ZF-Models - Zebrafish Models for Human Development and
Disease
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They were even able to observe this while it was
happening.
"The translucent larvae of the zebrafish can be
studied under a laser microscope over an extended period of time,"
reports Haass.
"If you add a color dye to the water to
specifically stain dying cells, you can even directly watch the neurons
as they die. That way, it should also be possible to watch and test
directly whether potential drugs actually do have a protective action.
“First experiments using newly developed drugs have
already confirmed this: One drug did have an effect in the living fish –
and was able to block the disease-related processes in the zebrafish
at
least to some extent."
The work has already been honored by those in the
field: In March, Dominik Paquet, PhD student at Haass' lab and first
author of the study, was honored with the Verum Award 2009 and the Leda
Hanin Award at the International Conference on Alzheimer's and
Parkinson's Diseases in Prague. Both distinctions are awarded to
outstanding young researchers.
Information Source:
Publication: "A transgenic zebrafish model
for Tauopathies allows in vivo imaging of neuronal cell death and drug
evaluation",
Dominik Paquet, Ratan Bhat, Astrid Sydow, Eva-Maria Mandelkow, Stefan
Berg, Sven Hellberg, Johanna Fälting, Martin Distel, Reinhard W. Köster,
Bettina Schmid, Christian Haass
Journal of Clinical Investigation Online, 13 April 2009
