Navigation Links
Broken cellular 'clock' linked to brain damage
Date:11/25/2013

A new discovery may help explain the surprisingly strong connections between sleep problems and neurodegenerative conditions such as Alzheimer's disease.

Sleep loss increases the risk of Alzheimer's disease, and disrupted sleeping patterns are among the first signs of this devastating disorder.

Scientists at Washington University School of Medicine in St. Louis and the University of Pennsylvania have shown that brain cell damage similar to that seen in Alzheimer's disease and other disorders results when a gene that controls the sleep-wake cycle and other bodily rhythms is disabled.

The researchers found evidence that disabling a circadian clock gene that controls the daily rhythms of many bodily processes blocks a part of the brain's housekeeping cycle that neutralizes dangerous chemicals known as free radicals.

"Normally in the hours leading up to midday, the brain increases its production of certain antioxidant enzymes, which help clean up free radicals," said first author Erik Musiek, MD, PhD, assistant professor of neurology at the School of Medicine. "When clock genes are disabled, though, this surge no longer occurs, and the free radicals may linger in the brain and cause more damage."

Musiek conducted the research in the labs of Garret FitzGerald, MD, chairman of pharmacology at the University of Pennsylvania, and of David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology at Washington University School of Medicine, who are co-senior authors.

The study appears Nov. 25 in The Journal of Clinical Investigation.

Musiek studied mice lacking a master clock gene called Bmal1. Without this gene, activities that normally occur at particular times of day are disrupted.

"For example, mice normally are active at night and asleep during the day, but when Bmal1 is missing, they sleep equally in the day and in the night, with no circadian rhythm," Musiek said. "They get the same amount of sleep, but it's spread over the whole day. Rhythms in the way genes are expressed are lost."

FitzGerald uses mice lacking Bmal1 to study whether clock cells have links to diabetes and heart disease. He has shown that clock genes influence blood pressure, blood sugar and lipid levels.

Several years ago, Musiek, who at the time was a neurology resident at the University of Pennsylvania, and FitzGeralddecided to investigate how knocking out Bmal1 affects the brain. Holtzman, who has published pioneering work on sleep and Alzheimer's disease, encouraged Musiek to continue and expand these studies when he came to Washington University as a postdoctoral fellow.

In the new study, Musiek found that as the mice aged, many of their brain cells became damaged and did not function normally. The patterns of damage were similar to those seen in Alzheimer's disease and other neurodegenerative disorders.

"Brain cell injury in these mice far exceeded that normally seen in aging mice," Musiek said. "Many of the injuries appear to be caused by free radicals, which are byproducts of metabolism. If free radicals come into contact with brain cells or other tissue, they can cause damaging chemical reactions."

This led Musiek to examine the production of key antioxidant enzymes, which usually neutralize and help clear free radicals from the brain, thereby limiting damage. He found levels of several antioxidant proteins peak in the middle of the day in healthy mice. However, this surge is absent in mice lacking Bmal1. Without the surge, free radicals may remain in the brain longer, contributing to the damage Musiek observed.

"We're trying to identify more specifics about how problems in clock genes contribute to neurodegeneration, both with and without influencing sleep," Musiek said. "That's a challenging distinction to make, but it needs to be made because clock genes appear to control many other functions in the brain in addition to sleeping and waking."


'/>"/>

Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

Related biology news :

1. A sea of broken promises
2. Could a diet high in fish and flax help prevent broken hips?
3. Putting the spring back in broken hearts
4. Salk scientists open new window into how cancers override cellular growth controls
5. Increased fructose consumption may deplete cellular energy in patients with obesity and diabetes
6. Cellular secrets of plant fatty acid production understood
7. Make or break for cellular tissues
8. A non-invasive intracellular thermometer with fluorescent proteins has been created
9. Groundbreaking discovery of the cellular origin of cervical cancer
10. BUSM study shows role of cellular protein in regulation of binge eating
11. Stealthy microscopy method visualizes E. coli sub-cellular structure in 3-D
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/21/2017)... 21, 2017 Der weltweite Biobanking-Sektor ... Nach einem Gespräch mit mehr als 50 Vertretern aus verschiedenen ... überwinden gilt, um diese Prognose zu realisieren. ... Zu ... der finanziellen Mittel für die Biobank, die Implementierung Zeit ...
(Date:2/14/2017)... , Feb. 14, 2017  Wake Forest Baptist ... as its new chief executive officer (CEO). Freischlag joins ... John D. McConnell , M.D., who last year ... at the Medical Center, after leading it since 2008. ... full scope of Wake Forest Baptist,s academic health system, ...
(Date:2/13/2017)... Former 9/11 Commission border counsel and Special ... Kephart of Identity Strategy Partners, LLP, today releases ... "Executive Order: Protecting the Nation From Foreign Terrorist Entry ... "As President Trump,s ,Travel Ban, Executive Order gains more ... the travel ban, it is important that our national ...
Breaking Biology News(10 mins):
(Date:2/23/2017)... (PRWEB) , ... February 23, 2017 , ... The ... announce a new partnership with Compass Research . GGI's mission is to advance ... vaccine to a child in need in honor of each clinical trial volunteer. The ...
(Date:2/23/2017)... SAN FRANCISCO , Feb. 23, 2017   ... Beyond Type 1, a not-for-profit advocacy and education group ... a grant from Beyond Type 1 to support ViaCyte,s ... and other insulin-requiring diabetes.  For more ... cell-derived cell replacement therapies with a focus on the ...
(Date:2/22/2017)... ... February 22, 2017 , ... ... acquired Kendall Research Systems, LLC (KRS) clinical development program. KRS is ... interface technology for research and clinical applications. The terms of the transaction were ...
(Date:2/22/2017)... , Feb. 22, 2017 Scientists propose in ... and organ damage in Gaucher and maybe other lysosomal ... and lower costs than current therapies. An ... Medical Center , which also included investigators from the ... report their data Feb. 22. The study was conducted ...
Breaking Biology Technology: