Featured Research

from universities, journals, and other organizations

Studying altered brain cells sheds light on epilepsy

Date:
April 26, 2010
Source:
Children's Hospital of Philadelphia
Summary:
Neuroscience researchers have zeroed in on a novel mechanism that helps control the firing of electrical signals among neurons. By isolating the molecular and electrical events that occur when this control is disrupted, the new research sheds light on epileptic seizures and potentially on other prominent diseases involving poorly regulated brain activity.

Neuroscience researchers have zeroed in on a novel mechanism that helps control the firing of electrical signals among neurons. By isolating the molecular and electrical events that occur when this control is disrupted, the new research sheds light on epileptic seizures and potentially on other prominent diseases involving poorly regulated brain activity.

"By better understanding the detailed events that occur in epilepsy, we are gaining knowledge that could ultimately lead to better treatments for epilepsy, and possibly for other neurological diseases," said neuroscientist Douglas A. Coulter, Ph.D., the corresponding author of the research study, from The Children's Hospital of Philadelphia. "Temporal lobe epilepsy, in particular, often resists current treatments."

Coulter's research group, collaborating with a team led by co-senior author Philip G. Haydon, Ph.D., of Tufts University School of Medicine, published a study online April 25 in the journal Nature Neuroscience.

In epilepsy, excessive signaling between neurons, a major type of brain cell that communicates electrical signals across gaps called synapses, can lead to epileptic seizures. However, another class of brain cells called glia can regulate those signals. Among the glia are star-shaped cells called astrocytes -- the particular focus of this research.

"This study shows that changes in astrocytes are key to brain dysfunction and opens the potential for novel therapeutic strategies in epilepsy," said Haydon, the Annetta and Gustav Grisard professor and chair of the department of neuroscience at Tufts.

The researchers focused on an abnormal condition called reactive astrocytosis, known to occur in many neurological diseases. The astrocytes swell to a large size and change expression levels of a number of proteins. The impact of reactive astrocytosis on brain function is difficult to investigate because it usually occurs in the context of brain inflammation and abnormal changes in surrounding cells.

The researchers solved this problem by using a virus to selectively cause reactive astrocytosis without triggering broader inflammation and brain injury, in a mouse model. They were able to focus on how the altered astrocytes affected specific synapses in neurons in the brain's hippocampus.

Studying the neuronal circuitry in brain slices from the mice, the study team found that changes in reactive astrocytes profoundly reduced the inhibitory control over brain signals.

Healthy brain function requires a delicate balance between excitation -- the firing of brain signals -- and inhibition, which limits those signals. An enzyme called glutamine synthetase is a key actor in a biological cycle that regulates the balance. The current study found that reactive astrocytosis reduces the supply of that enzyme, which in turn decreases inhibition and allows neurons to fire out of control.

"We already know that inhibition is a powerful force in the brain," said Coulter. "In epilepsy, inhibition is not working properly, and uncontrolled signaling leads to epileptic seizures. Because both disrupted inhibition and reactive astrocytosis are known to occur in other neurologic conditions, including many psychiatric disorders, traumatic brain injury, and neurodegenerative disorders such as Parkinson's disease, our findings may have wide implications."

Significantly, the researchers were able to dampen neuronal excitability in the animals' brain slices by adding glutamine, an amino acid that is depleted as a result of reduced glutamine synthetase activity. Coulter's and Haydon's teams are continuing animal studies to further investigate how this research may contribute to developing better treatments for epilepsy.

The National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health, both part of the National Institutes of Health, provided funding support for this study, as did the Epilepsy Foundation. Co-authors with Coulter and Haydon were first authors Pavel I. Ortinski, Ph.D., of Children's Hospital, and Jinghui Dong, Ph.D., of Tufts, as well as Alison Mungenast of Tufts; Cuiyong Yue and Hajime Takano, of Children's Hospital, and Deborah J. Watson of the University of Pennsylvania School of Medicine. Coulter also is on the faculty of the University of Pennsylvania School of Medicine. Haydon is also a member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.


Story Source:

The above story is based on materials provided by Children's Hospital of Philadelphia. Note: Materials may be edited for content and length.


Journal Reference:

  1. Pavel I Ortinski, Jinghui Dong, Alison Mungenast, Cuiyong Yue, Hajime Takano, Deborah J Watson, Philip G Haydon & Douglas A Coulter. Selective induction of astrocytic gliosis generates deficits in neuronal inhibition. Nature Neuroscience, April 25, 2010 DOI: 10.1038/nn.2535

Cite This Page:

Children's Hospital of Philadelphia. "Studying altered brain cells sheds light on epilepsy." ScienceDaily. ScienceDaily, 26 April 2010. <www.sciencedaily.com/releases/2010/04/100425151130.htm>.
Children's Hospital of Philadelphia. (2010, April 26). Studying altered brain cells sheds light on epilepsy. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2010/04/100425151130.htm
Children's Hospital of Philadelphia. "Studying altered brain cells sheds light on epilepsy." ScienceDaily. www.sciencedaily.com/releases/2010/04/100425151130.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Beijing Marathon Runners Brave Hazardous Air Pollution

Beijing Marathon Runners Brave Hazardous Air Pollution

AFP (Oct. 19, 2014) Tens of thousands of runners battled thick smog at the Beijing Marathon on Sunday, with some donning masks as the levels of PM2.5 small pollutant particles soared to 16 times the maximum recommended level. Duration: 00:54 Video provided by AFP
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