Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Common anesthetic may induce cell death, generation of Alzheimer's-associated protein

08.02.2007
A new study has found how one of the most commonly used anesthetics may produce Alzheimer's-like changes in the brain. Previous studies have shown that applying the anesthetic isoflurane to cultured neural cells can lead to generation of amyloid-beta protein -- the key component of senile plaques seen in the brains of Alzheimer's patients -- and to the cell-death process known as apoptosis.

In the Feb. 7 Journal of Neuroscience, researchers from Massachusetts General Hospital (MGH) and colleagues describe how isoflurane may set off a process in which A-beta generation and apoptosis interact with and magnify each other. Since this work was done in cell cultures, it is unknown whether the findings reflect a possible effect of the anesthetic on human brains.

"Our studies have shown that isoflurane may induce a vicious cycle of apoptosis, amyloid-beta generation, and further rounds of apoptosis leading to cell death," says Zhongcong Xie, MD, PhD, of the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND), the study's lead author. "If future studies support these findings, they suggest that caution be used in choosing this anesthetic for elderly patients, who already are at increased risk for Alzheimer's and for postoperative cognitive dysfunction." Xie is also associated with the MGH Department of Anesthesia and Critical Care.

Alzheimer's disease is characterized by plaques within the brain of amyloid-beta protein (A-beta), which is toxic to brain cells. A-beta is formed when the larger amyloid precursor protein (APP) is clipped by two enzymes -- beta-secretase, also known as BACE, and gamma-secretase -- to release the A-beta fragment. Normal processing of APP by an enzyme called alpha-secretase produces an alternative, non-toxic protein.

Some studies have indicated that general anesthesia may increase the risk of developing Alzheimer's disease. It also is known that a small but significant number of surgical patients experience a form of dementia in the postoperative period, but there is insufficient evidence of a direct connection between anesthesia and the risk of dementia. Previous articles -- including a recent report from the same research team -- have shown that isoflurane increases both A-beta generation and apoptosis in several types of cultured cells. The current study was designed to investigate the relationship between isoflurane-induced apoptosis and A-beta generation.

In a series of experiments, the researchers first found that applying isoflurane to cultured neural cells increased the activation of the enzyme caspase -- a key player in a pathway leading to apoptosis -- with no change in A-beta generation or APP processing. When they applied isoflurane to neural cells that express APP and had been treated with a caspase inhibitor, the expected changes in APP processing and A-beta generation were significantly reduced, indicating that caspase activation is essential to the pathway leading to A-beta generation and aggregation.

The researchers also found that isoflurane appears to raise levels of the A-beta-releasing enzymes BACE and gamma secretase and that generation of A-beta plaques further increases isoflurane-induced caspase activation. In addition, adding A-beta to neuronal cells that do not express APP also increased caspase activation in response to isoflurane. Overall, the study's results define molecular pathways by which isoflurane induces deposition of A-beta, both directly and via caspase activation, and by which A-beta deposits lead to further caspase activation and apoptosis.

"Even though our findings and those from other studies suggest that isoflurane may affect Alzheimer's pathogenesis, these experiments were performed in cultured cells only," says Rudolph Tanzi, PhD, director of the MGH-MIND Genetics and Aging Research Unit and senior author of the current paper. "We need to conduct in vivo studies before we can determine whether these results might be relevant to the development of delirium or Alzheimer's disease in human patients." Tanzi is a professor of Neurology at Harvard Medical School, where Xie is an assistant professor of Anesthesia. The researchers also plan to investigate whether other anesthetic agents may produce the same results seen with isoflurane, which is the only anesthetic tested in previous studies.

Sue McGreevey | EurekAlert!
Further information:
http://www.mgh.harvard.edu/

More articles from Studies and Analyses:

nachricht Physics of bubbles could explain language patterns
25.07.2017 | University of Portsmouth

nachricht Obstructing the ‘inner eye’
07.07.2017 | Friedrich-Schiller-Universität Jena

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA mission surfs through waves in space to understand space weather

25.07.2017 | Physics and Astronomy

Strength of tectonic plates may explain shape of the Tibetan Plateau, study finds

25.07.2017 | Earth Sciences

The dense vessel network regulates formation of thrombocytes in the bone marrow

25.07.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>