Navigation Links
Common anesthetic induces Alzheimer's-associated changes in mouse brains

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
Massachusetts General Hospital

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:
(Date:11/25/2015)... ... November 25, 2015 , ... Privately ... has undertaken significant expansion of its current state of the art research, development ... PharmaTech’s strategy to increase its manufacturing capacity as well as to support its ...
(Date:11/25/2015)... ... November 25, 2015 , ... Many people know of the ... gain, cold hands, and dry skin. But many people who find their cholesterol levels ... regimen instead of their thyroid, especially if they don’t have any of the other ...
(Date:11/25/2015)... ... November 25, 2015 , ... ... on providing comprehensive solutions involving adult stem cell therapies to patients with chronic ... the “Regenestem” name as a Registered Trademark (RTM). , Organizations are required to ...
(Date:11/25/2015)... ... November 25, 2015 , ... ... prices in an early celebration of the early holiday shopping season. Starting Wednesday ... each (normally $33.95 ea). Black Friday promotional pricing is in addition to any ...
(Date:11/24/2015)... ... November 24, 2015 , ... Eric C. ... the many benefits of the revolutionary BIOLASE WaterLase iPlus 2.0™ system. This advanced ... traditionally used by a dentist in Gettysburg, PA . From routine visits ...
Breaking Medicine News(10 mins):
(Date:11/25/2015)... announced the issue of United States patent No. 9,192,509  entitled: " Methods ... the company,s AVACEN 100 dry heat therapy medical device and specific methods of use, referred to ... Photo - ... ... ...
(Date:11/25/2015)... , Nov. 25, 2015 USP ... hazardous drug preparations (e.g. pharmacists, pharmacy technicians, nurses, ... veterinary technicians). The chapter also covers all entities ... (e.g., pharmacies, hospitals, other healthcare institutions, patient treatment ... --> --> What ...
(Date:11/25/2015)... Nov. 25, 2015  Mindray Medical ... MR ), a leading developer, ... worldwide, today announced that it will ... of shareholders at the Company,s Hong Kong office ... Prince Edward West Road, Mongkok KL, Hong ...
Breaking Medicine Technology: