Scientists uncover mechanism by which chronic stress causes brain disease
Chronic stress has long been linked with neurodegeneration. Scientists at USC now think they may know why.
The study, which has tremendous implications for understanding and treating Alzheimer's disease, was published in the June issue of The FASEB Journal.
Corresponding author Kelvin J. A. Davies, the James E. Birren Chair at the USC Davis School of Gerontology, and Professor of Molecular & Computational Biology in the USC Dornsife College, examined the brains of rats that had experienced psychological stresses and found high levels of the RCAN1 gene. Davies and his colleagues suggest that chronic stress physical or mental causes overexpression of RCAN1, in turn leading to neurodegenerative disease.
Think of a gene as a pattern or mold that generates specific proteins. For example, if 200 RCAN1 proteins are built where only 100 were needed, scientists would describe this as "overexpression" of the RCAN1 gene.
In a healthy person, the RCAN1 gene helps cells cope with stress. Overproduction, however, can eventually damage neurons, preventing the brain's signals from traveling and causing disease.
Chronic overproduction of RCAN1 causes hyper-phosphorylation of tau proteins in the brain.
Tau proteins stabilize microtubules, which are like the scaffolding used to build the brain's neurons. Previous research has shown that when the tau protein binds too much phosphate a process called hyperphosphorylation it forms snarls that prevent the brain's signals from effectively traveling.
"One can imagine that it becomes sticky and makes tangled scaffolding," Davies said.
These neurofibrillary tangles eventually choke the life out of neurons, killing off brain function a tiny piece at a time in what is outwardly recognized as degenerative brain disease.
Currently, there are two competing theories about the leading cause of neurodegeneration in Alzheimer's disease: overproduction of the Amyloid Beta peptide and tau hyperphosphorylation. Research in the Davies lab suggests that overexpression of RCAN1 is connected to both, and appears to unite the Amyloid Beta and tau theories of neurodegeneration.
"Both are clearly important, and RCAN1 could be the link," Davies said.
RCAN1 has been shown to be chronically overexpressed from birth in the brains of patients with Down syndrome. These patients develop neurofibrillary tangles and typically start to experience the onset of Alzheimer's disease around age 40.
Davies' lab has also shown a connection between too little RCAN1 production and Huntington's disease. "Our results suggest that the cellular levels of RCAN1 proteins must be kept within a fairly narrow range in order to avoid serious dysfunction," Davies said.
"By publishing this hypothesis, we hope to stimulate more research on the subject," he said.
Provided by University of Southern California
- New hope for treatment of neurodegenerative disorder Apr 20, 2009 | not rated yet | 0
- Researchers find critical link between Down syndrome and Alzheimer's disease Jan 12, 2011 | not rated yet | 0
- Acetylation may contribute to dementia and Alzheimer's disease Sep 22, 2010 | not rated yet | 0
- Scientists identify 'missing link' in process leading to Alzheimer's disease Feb 08, 2007 | not rated yet | 0
- Pin1 is beneficial in Alzheimer's disease, detrimental to some forms of dementia Apr 23, 2008 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
4 hours ago Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
(HealthDay)—Migraines and depression can each cause a great deal of suffering, but new research indicates the combination of the two may be linked to something else entirely—a smaller brain.
Neuroscience 15 hours ago | 4.3 / 5 (3) | 0 |
Moving objects attract greater attention – a fact exploited by video screens in public spaces and animated advertising banners on the Internet. For most animal species, moving objects also play a major ...
Neuroscience 18 hours ago | not rated yet | 0 |
It is known that signs of neurological disorders such as Alzheimer's and Huntington's disease can appear years before the disease becomes manifest; these signs take the form of subtle changes in the brain and behavior of ...
Neuroscience 18 hours ago | not rated yet | 0
Scientists have reversed behavioral and brain abnormalities in adult mice that resemble some features of schizophrenia by restoring normal expression to a suspect gene that is over-expressed in humans with ...
Neuroscience 20 hours ago | 5 / 5 (2) | 0 |
Researchers at Johns Hopkins have unraveled the molecular foundations of cocaine's effects on the brain, and identified a compound that blocks cravings for the drug in cocaine-addicted mice. The compound, already proven safe ...
Neuroscience 20 hours ago | not rated yet | 0 |
(Medical Xpress)—Researchers at the University of Virginia School of Medicine have identified a promising target for treating glioblastoma, one that appears to avoid many of the obstacles that typically frustrate efforts ...
28 minutes ago | not rated yet | 0 |
(Medical Xpress)—The first symptoms of major depression may be behavioral, but the common mental illness is based in biology—and not limited to the brain.
23 minutes ago | not rated yet | 0 |
(Medical Xpress)—Scientists at Emory Vaccine Center have shown that an immune regulatory molecule called IL-21 is needed for long-lasting antibody responses in mice against viral infections.
17 minutes ago | not rated yet | 0 |
Human breastmilk responds quickly to protect the child when there is an infection in mothers or babies, according to new international research led by The University of Western Australia.
29 minutes ago | not rated yet | 0
More than half of patients diagnosed with Non-Hodgkin Lymphoma (NHL) are now surviving the disease thanks to improved diagnosis and treatment, according to a new report1 from Cancer Research UK.
3 minutes ago | not rated yet | 0
To coincide with the broadcast of Jabbed: Love, Fear and Vaccines (SBS ONE, Sunday 26 May at 8.30pm) the first ever national survey on Australian attitudes to vaccination reveals surprising statistics including half of Australians ...
10 minutes ago | not rated yet | 0