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 Potential mechanism causing RBD 
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Joined: Fri Aug 11, 2006 1:46 pm
Posts: 4811
Location: SF Bay Area (Northern CA)
Post Potential mechanism causing RBD
RBD (REM sleep behavior disorder) is the acting out of dreams. Well over half of those with RBD develop PD (Parkinson's Disease), MSA (Multiple System Atrophy), or LBD (Lewy Body Dementia). Some Canadian research was published recently that is the first identification of a "potential mechanism for RBD." The researchers "show that deficits in glycine- and GABA(A)- mediated inhibition trigger the full spectrum of RBD symptoms" in mice.

I've copied the easily-understandable University of Toronto press release below. It talks about a "potential genetic cause" of RBD being found. And I've copied the harder-to-understand Journal of Neuroscience abstract further down.

Robin



Here's the press release:

Potential genetic cause of severe sleep disorder discovered, implications for Parkinson’s disease research
Posted on June 15, 2011
University of Toronto

TORONTO, ON – Researchers at the University of Toronto are the first to indentify a potential cause for a severe sleep disorder that has been closely linked to Parkinson’s disease and other neurodegenerative diseases.

“Our research is the first to establish a potential genetic link to human REM sleep behaviour disorder (RBD). That’s important because between 60 and 80 per cent of people diagnosed with human RBD develop Parkinson’s disease or other neurodegenerative disorders later in life,” says Dr. John Peever, lead author of the study that recently appeared in The Journal of Neuroscience.

Rapid-eye-movement sleep behaviour disorder (RBD) is most often characterized by violent movements that occur during dreaming sleep, also called rapid-eye-movement sleep. People who suffer from RBD do not experience normal muscle paralysis that prevents them from enacting their dreams and they often hurt themselves or their bed partners with their rapid, forceful movements. In some cases, patients need to be tied to their bed to prevent serious injury to themselves or their bedpartners.

Peever’s team focused on investigating a genetic cause of RBD because the underlying cause of this disorder is unknown. There is evidence indicating that reduced brain inhibition could cause RBD, so Peever’s team genetically reduced brain inhibition in mice and then recorded their sleep and muscle activity.

“We found that mice with reduced brain inhibition acted just like human RBD patients and they moved violently during REM sleep,” says Peever. “This link strongly suggests that patients with RBD may also have impaired brain inhibition.”

They also found that RBD symptoms in mice could be alleviated by giving them clonazepam – a drug used to treat human RBD.

Peever’s research underscores the importance of identifying a cause of RBD as 60 – 80 per cent of RBD sufferers subsequently develop Parkinson’s.

“Treating RBD could have direct implications for understanding and perhaps treating Parkinson’s disease,” says Peever.



And here's the abstract:

Journal of Neuroscience. 2011 May 11;31(19):7111-21.

Impaired GABA and Glycine Transmission Triggers Cardinal Features of Rapid Eye Movement Sleep Behavior Disorder in Mice.

Brooks PL, Peever JH.
Systems Neurobiology Laboratory, Department of Cell and Systems Biology, and Department of Physiology, University of Toronto, Toronto, Ontario, Canada.

Abstract
Rapid eye movement (REM) sleep behavior disorder (RBD) is a neurological disease characterized by loss of normal REM motor inhibition and subsequent dream enactment. RBD is clinically relevant because it predicts neurodegenerative disease onset (e.g., Parkinson's disease) and is clinically problematic because it disrupts sleep and results in patient injuries and hospitalization. Even though the cause of RBD is unknown, multiple lines of evidence indicate that abnormal inhibitory transmission underlies the disorder. Here, we show that transgenic mice with deficient glycine and GABA transmission have a behavioral, motor, and sleep phenotype that recapitulates the cardinal features of RBD. Specifically, we show that mice with impaired glycine and GABA(A) receptor function exhibit REM motor behaviors, non-REM muscle twitches, sleep disruption, and EEG slowing-the defining disease features. Importantly, the RBD phenotype is rescued by drugs (e.g., clonazepam and melatonin) that are routinely used to treat human disease symptoms. Our findings are the first to identify a potential mechanism for RBD-we show that deficits in glycine- and GABA(A)-mediated inhibition trigger the full spectrum of RBD symptoms. We propose that these mice are a useful resource for investigating in vivo disease mechanisms and developing potential therapeutics for RBD.

PubMed ID#: 21562273


Fri Jun 17, 2011 5:19 pm
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Joined: Fri Dec 31, 2010 3:07 pm
Posts: 1039
Location: Minnesota
Post Re: Potential mechanism causing RBD
Wow.

_________________
Jeanne, 68 cared for husband Coy, 86. RBD for 30+ years; LDB since 2003, Coy at home, in early stage, until death in 2012


Fri Jun 17, 2011 9:39 pm
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Joined: Fri Aug 11, 2006 1:46 pm
Posts: 4811
Location: SF Bay Area (Northern CA)
Post Re: Potential mechanism causing RBD
As we've realized time and time again, mice are not humans. But it is interesting that the same meds used to treat RBD in humans work in mice.


Sat Jun 18, 2011 1:18 am
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