Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mouse brain cells rapidly recover after Alzheimer’s plaques are cleared

21.01.2005


Brain cells in a mouse model of Alzheimer’s disease have surprised scientists with their ability to recuperate after the disorder’s characteristic brain plaques are removed.



Researchers at Washington University School of Medicine in St. Louis injected mice with an antibody for a key component of brain plaques, the amyloid beta (Abeta) peptide. In areas of the brain where antibodies cleared plaques, many of the swellings previously observed on nerve cell branches rapidly disappeared. "These swellings represent structural damage that seemed to be well established and stable, but clearing out the plaques often led to rapid recovery of normal structure over a few days," says senior author David H. Holtzman, M.D., the Charlotte and Paul Hagemann Professor and head of the Department of Neurology. "This provides confirmation of the potential benefits of plaque-clearing treatments and also gets us rethinking our theories on how plaques cause nerve cell damage."

Prior to the experiment, Holtzman and some other scientists had regarded plaque damage to nerve cells as a fait accompli--something that the plaques only needed to inflict on nerve cells once. According to Holtzman, the new results suggest that plaques might not just cause damage but also somehow actively maintain it.


The study, will appear in the Feb. 5 issue of the Journal of Clinical Investigation.

Lead author Robert Brendza, Ph.D., research instructor, began the experiment with one key question: how did clearance of brain plaques, made possible by the development of Abeta antibodies, affect the progression of Alzheimer’s disease? Through collaborations with researchers at other institutions, he had acquired several key techniques and technologies that allowed him to closely track changes in live brain cells in mice with an Alzheimer’s-like condition.

The mice he used for the study had two mutations. One, utilized by scientists at Eli Lilly, causes amyloid plaques to build up, creating the Alzheimer’s-like condition. The second, developed by scientists at Washington University, causes some of the mouse brain cells to produce a dye that allowed Brendza to obtain detailed images of nerve cell branches.

To correlate brain cell changes with plaque development, Brendza injected another dye, developed by scientists at the University of Pittsburgh, that temporarily sticks to amyloid. He showed that as the plaques appeared, nearby branches of nerve cells developed bumps and swellings. "If you look under the electron microscope at these swellings, they are filled with abnormal amounts of different types of cellular parts known as organelles," Holtzman explains. "Normally any given segment of a nerve cell branch would have only very small amounts of these organelles."

Nerve cells move organelles along their branches as a part of their regular function. Holtzman suspects that this transport breaks down in the mice, leading to pileups that become swellings. Scientists have previously demonstrated that such swellings make it difficult or impossible for nerve-cell branches to send signals.

After showing that the swellings were mostly stable in number and size over the course of three to seven days, Brendza injected Abeta antibodies directly onto the surface of the mouse brains. In the region of the injection, the antibodies cleared the plaques, confirming earlier research results. Then Brendza closely monitored the swellings for three days. "We thought that clearing the plaques would halt the progression of the damage--stop the development of new swellings," says Brendza. "But what we saw was much more striking: in just three days, there were 20 to 25 percent reductions in the number or size of the existing swellings."

The nerve cells’ rapid ability to regain normal structure has Holtzman and Brendza wondering if the nerve cells are constantly trying to restore their normal structure. If so, that recuperative effort must somehow be countered on an ongoing basis by the effects of the plaques. More research is needed to determine if similar effects will occur in humans. Abeta antibodies are currently being considered for use in Alzheimer’s patients in clinical trials.

In the mice, the largest swellings were least likely to heal. Brendza plans to look into whether additional treatment can prompt their recovery. Holtzman and Brendza plan to continue using the mouse model to study disease treatments and the cellular abnormalities caused by their Alzheimer’s-like condition. "For example, we’d like to know what’s going wrong in the nerve cell branches that get these swellings," Holtzman says. "Is it really a cellular transport problem, or do the swellings result from the plaques’ effects on nearby support cells? Or is it something else?"

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Stiffness matters
22.02.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Separate brain systems cooperate during learning, study finds
22.02.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Stiffness matters

22.02.2018 | Life Sciences

Magnetic field traces gas and dust swirling around supermassive black hole

22.02.2018 | Physics and Astronomy

First evidence of surprising ocean warming around Galápagos corals

22.02.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>