Featured Research

from universities, journals, and other organizations

Possible Mechanistic Link Between Stress And The Development Of Alzheimer Tangles

Date:
June 15, 2007
Source:
Salk Institute
Summary:
Subjecting mice to repeated emotional stress, the kind we experience in everyday life, may contribute to the accumulation of neurofibrillary tangles, one of the hallmarks of Alzheimer's disease.

Subjecting mice to repeated emotional stress, the kind we experience in everyday life, may contribute to the accumulation of neurofibrillary tangles, one of the hallmarks of Alzheimer's disease, report researchers at the Salk Institute for Biological Studies. While aging is still the greatest risk factor for Alzheimer's disease, a number of studies have pointed to stress as a contributing factor.

Related Articles


"A long-term study of about 800 members of religious orders had found that the people who were most prone to stress were twice as likely to develop Alzheimer's disease, but the nature of the link between the two has been elusive," says Paul E. Sawchenko, Ph.D., a professor in the Neuronal Structure and Function Laboratory, who led a phalanx of Salk researchers contributing to the current study.

The group's findings, detailed in this week's Journal of Neuroscience, suggest that the brain-damaging effects of negative emotions are relayed through the two known corticotropin-releasing factor receptors, CRFR1 and CRFR2, which are part of a central switchboard that mediates the body's responses to stress and stress-related disorders.

Alzheimer's disease is defined by the accumulation of amyloid plaques and neurofibrillary tangles. While plaques accumulate outside of brain cells, tangles litter the inside of neurons. They consist of a modified form of the tau protein, which--in its unmodified form--helps to stabilize the intracellular network of microtubules. In Alzheimer's disease, as well as various other neurodegenerative conditions, phosphate groups are attached to tau. As a result, tau looses its grip on the microtubules, and starts to collapse into insoluble protein fibers, which ultimately cause cell death.

Previous studies had shown that extreme physiological stress, such as plunging mice into ice water or starving them for three days, can induce tau phosphorylation. "But what we wanted to know was whether exposure to milder stress, of the kind we experience in our daily lives, can induce tau phosphorylation," explains senior research associate and first author Robert A. Rissman, Ph.D.

Restraining mice for half an hour, a situation that replicates the body's reaction to low-level anxiety, fear or social stress, resulted only in a transient phosphorylation of tau. However, when Rissman simulated chronic stress by repeating the procedure every day for two weeks, the modification lasted long enough to let tau molecules tumble off the cytoskeleton and pile up in insoluble heaps of protein.

The first thing you consider when you think about stress-induced changes in the brain is glucocorticoids because they are such pervasive mediators of stress responses, says Rissman. But even without available glucocorticoids, tau was still modified under stressful conditions and he had to look elsewhere. "The next obvious candidate was the CRF system, which has been broadly implicated in many kinds of stress adaptation," he says.

So, Rissman and Sawchenko teamed up with their Salk colleagues Kuo-Fen Lee, Ph.D., and Wylie W. Vale, Ph.D., both professors in the Clayton Foundation Laboratories for Peptide Biology. Vale, Lee and their colleagues have been instrumental in piecing together a global view of how the corticotropin-releasing family of molecules regulate our bodies' responses to physiological and emotional stress.

Lee made available his mice that had been genetically engineered to lack either CRFR1 or CRFR2. "And sure enough, the CRF receptors turn out to be integrally and differentially involved," says Sawchenko. In the absence of CRFR1, stress-induced tau phosphorylation was abrogated, while in mice missing CRFR2 the effect was amplified. Pharmacological studies with small molecule inhibitors replicated the effect.

Currently, several companies are actively pursuing small molecule drugs that bind CRF receptors and a few of them are already in stage 2 clinical trials for depression and other mood disorders. "We may have discovered another application. Such drugs could have a prophylactic effect or delay the progression of Alzheimer's disease," Sawchenko says.


Story Source:

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


Cite This Page:

Salk Institute. "Possible Mechanistic Link Between Stress And The Development Of Alzheimer Tangles." ScienceDaily. ScienceDaily, 15 June 2007. <www.sciencedaily.com/releases/2007/06/070614155344.htm>.
Salk Institute. (2007, June 15). Possible Mechanistic Link Between Stress And The Development Of Alzheimer Tangles. ScienceDaily. Retrieved November 29, 2014 from www.sciencedaily.com/releases/2007/06/070614155344.htm
Salk Institute. "Possible Mechanistic Link Between Stress And The Development Of Alzheimer Tangles." ScienceDaily. www.sciencedaily.com/releases/2007/06/070614155344.htm (accessed November 29, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Saturday, November 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Tryptophan Isn't Making You Sleepy On Thanksgiving

Tryptophan Isn't Making You Sleepy On Thanksgiving

Newsy (Nov. 27, 2014) — Tryptophan, a chemical found naturally in turkey meat, gets blamed for sleepiness after Thanksgiving meals. But science points to other culprits. Video provided by Newsy
Powered by NewsLook.com
Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) — A new study links greater authority with increased depressive symptoms among women in the workplace. Video provided by Newsy
Powered by NewsLook.com
Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) — Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) — Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. 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