Featured Research

from universities, journals, and other organizations

Epilepsy drug target implications for sleep disruption in brain disorders

Date:
April 1, 2014
Source:
Perelman School of Medicine at the University of Pennsylvania
Summary:
A study using the mutant fruitfly sleepless confirmed that the enzyme GABA transaminase, a target of some epilepsy drugs, contributes to sleep loss. 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.

This image shows the proximity of GABA-producing neurons (green) and glia (purple) in the fly brain.
Credit: Amita Sehgal, Ph.D., Perelman School of Medicine, University of Pennsylvania

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.

Related Articles


"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.


Story Source:

The above story is based on materials provided by Perelman School of Medicine at the University of Pennsylvania. Note: Materials may be edited for content and length.


Journal Reference:

  1. W-F Chen, S Maguire, M Sowcik, W Luo, K Koh, A Sehgal. A neuron–glia interaction involving GABA transaminase contributes to sleep loss in sleepless mutants. Molecular Psychiatry, 2014; DOI: 10.1038/mp.2014.11

Cite This Page:

Perelman School of Medicine at the University of Pennsylvania. "Epilepsy drug target implications for sleep disruption in brain disorders." ScienceDaily. ScienceDaily, 1 April 2014. <www.sciencedaily.com/releases/2014/04/140401142127.htm>.
Perelman School of Medicine at the University of Pennsylvania. (2014, April 1). Epilepsy drug target implications for sleep disruption in brain disorders. ScienceDaily. Retrieved January 31, 2015 from www.sciencedaily.com/releases/2014/04/140401142127.htm
Perelman School of Medicine at the University of Pennsylvania. "Epilepsy drug target implications for sleep disruption in brain disorders." ScienceDaily. www.sciencedaily.com/releases/2014/04/140401142127.htm (accessed January 31, 2015).

Share This


More From ScienceDaily



More Mind & Brain News

Saturday, January 31, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

NFL Concussions Down; Still on Parents' Minds

NFL Concussions Down; Still on Parents' Minds

AP (Jan. 30, 2015) The NFL announced this week that the number of game concussions dropped by a quarter over last season. Still, the dangers of the sport still weigh on players, and parents&apos; minds. (Jan. 30) Video provided by AP
Powered by NewsLook.com
Study Shows Newborn Chicks Count From Left to Right Just Like Humans

Study Shows Newborn Chicks Count From Left to Right Just Like Humans

Buzz60 (Jan. 30, 2015) Researchers for the first time identified human&apos;s innate preference for associating low and high numbers with the left and right respectively in another species. Jen Markham (@jenmarkham) explains. Video provided by Buzz60
Powered by NewsLook.com
Best Mood Elevating, Feel Good Shakes & Smoothies

Best Mood Elevating, Feel Good Shakes & Smoothies

Buzz60 (Jan. 30, 2015) You can elevate your mood by having a meal in a glass. Fitness and nutrition expert John Basedow (@JohnBasedow) offers the best &apos;feel good&apos; smoothies and shakes chock full of depression-relieving ingredients...including apples, berries, lemons, cucumbers, papaya, kiwi, spinach, kale, whey protein, matcha, ginger, turmeric and cinnamon. Video provided by Buzz60
Powered by NewsLook.com
Poll Says Firstborn Is Responsible, Youngest Is Funnier

Poll Says Firstborn Is Responsible, Youngest Is Funnier

Newsy (Jan. 30, 2015) According to a poll out of the U.K., eldest siblings feel more responsible and successful than their younger siblings. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins