Navigation Links
Fruitfly study: Epilepsy drug target implications for sleep disruption in brain disorders
Date:4/1/2014

PHILADELPHIA A new study in a mutant fruitfly called sleepless (sss) confirmed that the enzyme GABA transaminase, which is the target of some epilepsy drugs, contributes to sleep loss. The findings, published online in Molecular Psychiatry, were led by Amita Sehgal, PhD, head of the Chronobiology Program at the University of Pennsylvania's Perelman School of Medicine. The findings shed light on mechanisms that may be shared between sleep disruption and some neurological disorders. A better understanding of this connection could enable treatments that target both types of symptoms and perhaps provide better therapeutic efficacy.

"Epilepsy is essentially an increase-in-firing disorder of the brain and maybe a decrease in activity of the neurotransmitter GABA, too," says Sehgal, who is also a professor of Neuroscience and an investigator with the Howard Hughes Medical Institute (HHMI). "This connects our work to drugs that inhibit GABA transaminase. Changes in GABA transaminase activity are implicated in epilepsy and some other psychiatric disorders, which may account for some of the associated sleep problems."

The team looked at the proteomics of the sss mutant brain a large-scale study of the structure and function of related proteins -- and found that GABA transaminase is increased in the sss brain compared to controls. This enzyme breaks down GABA, so GABA is decreased in the sss brain. Because GABA promotes sleep, there is a decrease in sleep in the sss mutant fly, as the name implies.

The relationship between the SSS protein and GABA is not fully understood. The SSS protein controls neural activity, and its absence results in increased neural firing, which likely uses up a lot of energy, says Sehgal. GABA transaminase works in the mitochondria, the energy-production organelle in the glial cells of the brain, which provide fuel for neurons. The large energy demand created by the increased neural firing in sss brains probably alters mitochondrial metabolism, including GABA transaminase function in glia.

In the sss mutant fly, there is a stream of connections that leads to its signature loss of sleep: The sss mutant has increased neuron firing caused by downregulation of a potassium channel protein called Shaker. Recently, the Sehgal lab showed that SSS also affects activity of acetylcholine receptors. Both of these actions may directly cause an inability to sleep. In addition, increased energy demands on glia, which increase GABA transaminase and decrease GABA, may further contribute to sleep loss. On the other hand, if GABA is increased, then sleep is increased, as in flies that lack GABA transaminase.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. IU, Regenstrief study: New noninvasive colorectal cancer screening tool highly accurate
2. Study: MLB pitchers dont regain performance level after Tommy John surgery
3. Study: Resilience in parents of children undergoing stem cell transplant
4. U of Maryland study: Partnership may help address cancer, health disparities
5. Study: Oropharyngeal cancer on the rise in young adults
6. Johns Hopkins study: Traumatic spinal cord injuries on the rise in US
7. Regenstrief, IU study: Half of hospitalized adults over 65 need surrogate decision-makers
8. Study: Possible new druggable target in Ewings Sarcoma
9. Study: Autophagy predicts which cancer cells live and die when faced with anti-cancer drugs
10. Study: Living Room offers alternative treatment for emotional distress
11. Study: Half of black males, 40 percent of white males arrested by age 23
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Fruitfly study: Epilepsy drug target implications for sleep disruption in brain disorders
(Date:3/28/2020)... ... 2020 , ... With social distancing, or more accurately physical ... people of all ages are challenged to find different ways to connect socially. ... best of times—the physical distance mandated to prevent the pandemic’s spread can be ...
(Date:3/28/2020)... ... March 28, 2020 , ... Confluent Health is ... physical therapist-owned rehabilitation company since 1985 specializing in the treatment of orthopedic, sports, ... started more than 30 years ago, we have been committed to providing excellent ...
(Date:3/22/2020)... ... 21, 2020 , ... The modular construction industry, led by ... have been working with state and federal officials on ways to support housing ... of modular construction to address the nation’s affordable housing crisis well before the ...
(Date:3/20/2020)... ... March 20, 2020 , ... My heart goes out to those across our ... lost a loved one recently through similar circumstances - underlying conditions compounded by a ... felt a gamut of negative emotions just like many have: fear, anxiety, uncertainty. In ...
(Date:3/19/2020)... ... March 19, 2020 , ... For weeks, SignatureCare Emergency Center has been ... this week, it announced that while we are still short of some critical safety ... wait for our preparedness measures to be complete. , The Houston, TX based company ...
Breaking Medicine News(10 mins):
(Date:3/16/2020)... ... , ... In the wake of the COVID-19 pandemic, Curogram , the ... efforts to help the containment of the global disease with its virtual clinic, two-way ... EMR system. , “Our goal is to minimize exposure and maximize providers’ resources ...
(Date:3/16/2020)... ... March 16, 2020 , ... MCH has been tracking trends and compiling ... and maintains a comprehensive database of district and school institution, personnel, enrollment and ... and communities. The COVID-19 impact map and related data can be used by ...
(Date:3/16/2020)... ... March 16, 2020 , ... The American Academy of ... Beth Fasano, MD, MSPH, FAAAAI. , The AAAAI is the largest professional ... with a special interest in the research and treatment of allergic and immunologic ...
Breaking Medicine Technology: