PD-like sleep and motor problems observed in alpha-synuclein mutant mice

June 7, 2013, IOS Press

The presence of Lewy bodies in nerve cells, formed by intracellular deposits of the protein α-synuclein, is a characteristic pathologic feature of Parkinson's Disease (PD). In the quest for an animal model of PD that mimics motor and non-motor symptoms of human PD, scientists have developed strains of mice that overexpress α-synuclein. By studying a strain of mice bred to overexpress α-synuclein via the Thy-1 promoter, scientists have found these mice develop many of the age-related progressive motor symptoms of PD and demonstrate changes in sleep and anxiety. Their results are published in the latest issue of Journal of Parkinson's Disease.

PD is the second most common in the United States, affecting approximately one million Americans and five million people worldwide. Its prevalence is projected to double by 2030. The most obvious symptoms are movement-related, such as involuntary shaking and ; non-motor symptoms, such as increases in anxiety and , can appear prior to the onset of motor symptoms. Although the drug levodopa can relieve some symptoms, there is no cure – intensifying the pressure to find an animal model that can help clarify the pathological processes underlying human PD and find new medications to treat the pathology and/or relieve symptoms.

Investigators at the National Institute on Aging compared wild type mice with specially bred mice that were transgenic for the A53T mutation of the human α-synuclein (SNCA) gene under the control of a human thymus cell antigen 1, theta (THY-1) promoter. As the mice aged, their on a rotarod test (which measures how long the mouse can remain on a rotating rod) became impaired and the length of their strides were significantly shorter than the wild type .

The study also found that SNCA mice displayed fragmented nighttime compared to wild type controls and appeared to have a reduced overall . "Despite the prevalence of abnormal sleep patterns in PD, very few studies to date have outlined sleep disturbances in animal models of PD," says Sarah M. Rothman, PhD, a researcher with the National Institute on Aging, in Baltimore, MD.

Many PD patients typically show an increase in anxiety and depression, and in this respect the SNCA mouse model did not replicate the human condition. SNCA mice displayed an early and significant decrease in anxiety-like behavior that persisted throughout their lifespan, as shown by both open field and elevated plus maze tests (in which mice have the choice of spending time in open or closed arms of a maze). Other rodent models that utilize changes in expression of α-synuclein have also reported lower anxiety levels. The authors suggest that higher levels of serotonin found in the hypothalamus of the SNCA mice may be associated with the reduced anxiety observed.

The authors say it is important to remember that the SNCA "model utilizes the presence of a mutation that only occurs very rarely in PD. While all PD patients display α-synuclein pathology, they do not all express the mutated form of the protein," says Dr. Rothman.

Explore further: Diabetes drug tested in Parkinson's disease patients

Related Stories

Diabetes drug tested in Parkinson's disease patients

May 20, 2013
Parkinson's disease (PD) is a degenerative neurological disorder marked by a progressive loss of motor control. Despite intensive research, there are currently no approved therapies that have been demonstrated to alter the ...

Researchers provide rationale for use of targeted immunotherapy in sarcomatoid lung carcinomas

May 28, 2013
Sarcomatoid carcinomas of the lung include rare subtypes of poorly differentiated non–small-cell lung carcinomas of high grade and aggressive behavior. The biology of these neoplasms is poorly understood and these tumors ...

Blocking LRRK2 activity is not a simple answer to Parkinson's disease

May 29, 2012
Mutations in the LRRK2 gene are the most common cause of genetic Parkinson's disease (PD). New research published in BioMed Central's open access journal Molecular Neurodegeneration demonstrates that loss of function of LRRK2 ...

Parkinson's disease protein causes disease spread and neuron death in healthy animals

November 15, 2012
Understanding how any disease progresses is one of the first and most important steps towards finding treatments to stop it. This has been the case for such brain-degenerating conditions as Alzheimer's disease. Now, after ...

Shedding light on early Parkinson's disease pathology

April 1, 2013
In a mouse model of early Parkinson's disease (PD), animals displayed movement deficits, loss of tyrosine-hydroxylase (TH)-positive fibers in the striatum, and astro-gliosis and micro-gliosis in the substantia nigra (SN), ...

Flies model a potential sweet treatment for Parkinson's disease

April 6, 2013
Researchers from Tel Aviv University describe experiments that could lead to a new approach for treating Parkinson's disease (PD) using a common sweetener, mannitol. This research is presented today at the Genetics Society ...

Recommended for you

Early synaptic dysfunction found in Parkinson's Disease

May 24, 2018
Northwestern Medicine scientists identified a cellular mechanism that leads to neurodegeneration in patients with Parkinson's disease, according to a study published in Proceedings of the National Academy of Sciences.

Study uncovers cause of pesticide exposure, Parkinson's link

May 23, 2018
A new University of Guelph study has discovered why exposure to pesticides increases some people's risk of developing Parkinson's disease.

Link between tuberculosis and Parkinson's disease discovered

May 22, 2018
The mechanism our immune cells use to clear bacterial infections like tuberculosis (TB) might also be implicated in Parkinson's disease, according to a new collaborative study led by scientists from the Francis Crick Institute ...

Link between IBD and Parkinson's might allow doctors to slow down condition

May 21, 2018
Doctors may be able to modify or slow down the progress of the neurological condition Parkinson's disease in the future by spotting signs of it in patients with inflammatory bowel disease (IBD), suggest a study published ...

Untangling brain neuron dysfunction in Parkinson's disease and dementia with Lewy bodies

May 10, 2018
A decay of brain function is a hallmark of Parkinson's disease and dementia with Lewy bodies, or DLB. Specifically, cognitive dysfunction defines DLB, and nearly eight of every 10 Parkinson's patients develop dementia.

Diverse Parkinson's-related disorders may stem from different strains of same protein

May 9, 2018
Different Parkinson's-related brain disorders, called synucleionpathies, are characterized by misfolded proteins embedded in cells. Researchers in the Perelman School of Medicine at the University of Pennsylvania found that ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.