Featured Research

from universities, journals, and other organizations

Common Anesthetic Induces Alzheimer's-associated Changes In Mouse Brains

Date:
November 14, 2008
Source:
Massachusetts General Hospital
Summary:
For the first time researchers have shown that a commonly used anesthetic can produce changes associated with Alzheimer's disease in the brains of living mammals, confirming previous laboratory studies. Scientists have shown how administration of the gas isoflurane can lead to generation of the toxic amyloid-beta protein in the brains of mice.

For the first time researchers have shown that a commonly used anesthetic can produce changes associated with Alzheimer's disease in the brains of living mammals, confirming previous laboratory studies.

Related Articles


In their Annals of Neurology report, which has received early online release, a team of Massachusetts General Hospital (MGH) investigators shows how administration of the gas isoflurane can lead to generation of the toxic amyloid-beta (A-beta) protein in the brains of mice.

"These are the first in vivo results indicating that isoflurane can set off a time-dependent cascade inducing apoptosis [cell death] and enhanced levels of the Alzheimer's-associated proteins BACE and A-beta," says Zhongcong Xie, MD, PhD, of the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND) and the MGH Department of Anesthesia and Critical Care, the study's lead and corresponding author. "This work needs to be confirmed in human studies, but it's looking like isoflurane may not be the best anesthesia to use for patients who already have higher A-beta levels, such as the elderly and Alzheimer's patients."

Alzheimer's disease is characterized by deposition of A-beta plaques within the brain. The A-beta protein 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.

Several studies have suggested that surgery and general anesthesia may increase the risk of developing Alzheimer's disease, and it is well known that a small but significant number of surgical patients experience a transient form of dementia in the postoperative period. Last year the MGH team showed that applying isoflurane to cultured neural cells increased activation of the cell-death protein caspase and raised levels of BACE and gamma-secretase as part of a pathway leading to the generation of A-beta. The current study was designed to see if the same process takes place in mice.

Neurologically normal mice received isoflurane for two hours at doses comparable to what would be administered to human patients. Their brains were examined 2, 6, 12 and 24 hours after they received the anesthesia and compared with the brains of control mice. Results at 6 hours showed that caspase levels were elevated and BACE had modestly increased in mice that received isoflurane. At 12 hours moderate caspase activation persisted, and BACE levels were even higher in the treated mice; and at 24 hours BACE levels were more than four times higher than in controls, and A-beta levels had also risen, while caspase activation had fallen off.

Another group of mice had been treated for seven days with the drug clioquinol before the two-hour isoflurane administration. Laboratory studies have found that clioquinol inhibits the aggregation of A-beta into neurotoxic deposits, and a clioquinol derivative is currently in clinical trials as an Alzheimer's treatment drug. Six hours after they received isoflurane, caspase levels in the clioquinol-treated mice were significantly less than in other animals that had received the anesthetic, suggesting both that A-beta aggregation contributes to a vicious cycle of further cell death – echoing a finding from the team's 2007 study – and that a drug like clioquinol might block isoflurane's neurotoxic effects.

"This study cannot tell us about the long-term effects of isoflurane administration; that's something we will examine in future investigations," notes Xie, who is an assistant professor of Anesthesia at Harvard Medical School (HMS) and director of the Geriatric Anesthesia Research Unit in the MGH Department of Anesthesia and Critical Care.

"Until we can directly assess the impact of isoflurane on biomarkers like A-beta levels in the plasma or cerebrospinal fluid of human patients, we cannot conclusively determine its role in increasing the risk for Alzheimer's or postoperative dementia," adds Rudolph Tanzi, PhD, director of the MGH-MIND Genetics and Aging Research Unit, senior author of the study, and the Joseph P. and Rose F. Kennedy Professor of Neurology at HMS.

Gregory Crosby, MD, of Brigham and Women's Hospital (BWH) is a co-corresponding author of the Annals of Neurology paper. Additional co-authors are Yuanlin Dong, Guohua Zhang, and Bin Zhang, MGH-MIND and MGH Anesthesia; Robert D. Moir, PhD, MGH-MIND; Matthew Frosch, MD, PhD, MGH Neurology, and Deborah Culley, MD, BWH.

The study was supported by grants from the National Institutes of Health, the American Geriatrics Society, the Alzheimer's Association, Harvard University and the Cure Alzheimer's Fund. Tanzi is a co-founder, consultant and holds equity in Prana Biotechnology, Ltd, the company conducting a clinical trial of clioquinol derivative PBT2. Xie is a consultant of Baxer Healthcare, the company that produces isoflurane. Neither company supported or had any other connection with the current study.


Story Source:

The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.


Cite This Page:

Massachusetts General Hospital. "Common Anesthetic Induces Alzheimer's-associated Changes In Mouse Brains." ScienceDaily. ScienceDaily, 14 November 2008. <www.sciencedaily.com/releases/2008/11/081112124410.htm>.
Massachusetts General Hospital. (2008, November 14). Common Anesthetic Induces Alzheimer's-associated Changes In Mouse Brains. ScienceDaily. Retrieved March 1, 2015 from www.sciencedaily.com/releases/2008/11/081112124410.htm
Massachusetts General Hospital. "Common Anesthetic Induces Alzheimer's-associated Changes In Mouse Brains." ScienceDaily. www.sciencedaily.com/releases/2008/11/081112124410.htm (accessed March 1, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, March 1, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Rehab Robot Helps Restore Damaged Muscles and Nerves

Rehab Robot Helps Restore Damaged Muscles and Nerves

Reuters - Innovations Video Online (Mar. 1, 2015) A rehabilitation robot prototype to help restore deteriorated nerves and muscles using electromyography and computer games. Ben Gruber reports. Video provided by Reuters
Powered by NewsLook.com
Could a $34 Smartphone Device Improve HIV Diagnosis in Africa?

Could a $34 Smartphone Device Improve HIV Diagnosis in Africa?

Reuters - Innovations Video Online (Feb. 27, 2015) A dongle that plugs into a Smartphone mimics a lab-based blood test for HIV and syphilis and can detect the diseases in 15 minutes, say researchers. Tara Cleary reports. Video provided by Reuters
Powered by NewsLook.com
Doctor Says Head Transplants Possible Within Two Years

Doctor Says Head Transplants Possible Within Two Years

Buzz60 (Feb. 27, 2015) An Italian doctor is saying he could stick someone&apos;s head onto someone else&apos;s body. Patrick Jones (@Patrick_E_Jones) reports. Video provided by Buzz60
Powered by NewsLook.com
How Your Dentist Could Help Screen You For Diabetes

How Your Dentist Could Help Screen You For Diabetes

Newsy (Feb. 27, 2015) A new study from researchers at New York University suggests dentists could soon use blood samples taken from patients&apos; mouths to test for diabetes. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins