Navigation Links
Common anesthetic induces Alzheimer's-associated changes in mouse brains
Date:11/12/2008

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. 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.


'/>"/>

Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

Related medicine news :

1. UK junior doctors gaining less experience of common procedures
2. New insights into common knee injuries
3. High and mighty: first common height gene identified by researchers behind obesity gene finding
4. Figure Skater Peggy Fleming, HealthSaver Says: Take Pains For Back Strains, 2nd Most Common Doctor Complaint
5. Exelixis Commences Public Offering of Common Stock
6. Common misdiagnosis: most women believe they have a yeast infection when they dont
7. Business Executives Discuss National Health Care Reform at Conference Sponsored by The Century Foundation, with Support from The Commonwealth Fund, and AARP
8. New Expert Report Dispels Common Myths About Aspartame
9. Common Foot Myths Trip Us Up
10. AHPC Holdings, Inc. Announces Intent to Deregister Common Stock With Securities and Exchange
11. Allergy-Induced Asthma More Common in Affluent Countries
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/11/2016)... ... , ... The president released a FY 2017 budget request on Tuesday that ... the cost burden to military beneficiaries. , MOAA’s president, retired Air Force Lt. ... including limited quantifiable benefit fixes mixed with numerous beneficiary fee hikes. , “We were ...
(Date:2/11/2016)... ... 2016 , ... The Chartis Group, a national advisory services ... the “2015/2016 Best in KLAS: Software and Services” report in two categories: IT ... insights firm on a global mission to improve healthcare delivery by amplifying the ...
(Date:2/11/2016)... (PRWEB) , ... February 11, 2016 , ... ... to reverse diabetes has been gearing up for their simultaneous grand openings in ... It’s about right now that you’re probably wondering, is reversing diabetes possible? According ...
(Date:2/11/2016)... (PRWEB) , ... February 11, 2016 , ... ... advocates will discuss how to improve care by making data on heart procedures ... disease. The Summit on Transparency and Public Reporting of Pediatric and Congenital Heart ...
(Date:2/11/2016)... ... February 11, 2016 , ... Thermi™, a world leader ... to announce the promotions of Allison Kelly to executive vice president of the ... vice president of North American capital sales, and Wendy Oseas to vice president ...
Breaking Medicine News(10 mins):
(Date:2/11/2016)... , Feb. 11, 2016 Potrero Medical, Inc., ... pleased to announce the appointment of George M. Rapier, ... San Antonio, TX , WellMed is one of ... 200,000 patients and HMO members in Texas ... in 1990 out of his own internal medicine practice, he ...
(Date:2/11/2016)... , Feb. 11, 2016  NOIT™ Research LLC, a ... "Gift of Change" campaign to assist needy families in ... such unit sold between February 10, 2016 and March ... a needy family. The NOIT is an auditory stimulus ... individuals develop language skills. Beth Shier ...
(Date:2/11/2016)... , Feb. 11, 2016  MiMedx Group, Inc. ... utilizing human amniotic membrane and other birth tissues, human ... to develop and market advanced products and therapies, announced ... Markets, 2016 Global Healthcare Conference in New ... and CEO, Michael J. Senken , Chief Financial ...
Breaking Medicine Technology: