Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Studying altered brain cells sheds light on epilepsy

26.04.2010
Modified cells disrupt signal control, may permit seizures

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 today 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.

"Selective induction of astrocytic gliosis generates deficits in neuronal inhibition," Nature Neuroscience, published online April 25, 2010. http://dx.doi.org/10.1038/nn.2535

About The Children's Hospital of Philadelphia

The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 460-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.

About Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences

Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, biomedical sciences, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. Tufts University School of Medicine and the Sackler School undertake research that is consistently rated among the highest in the nation for its impact on the advancement of medical science.

John Ascenzi | EurekAlert!
Further information:
http://www.chop.edu
http://www.tufts.edu

More articles from Life Sciences:

nachricht Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)

nachricht CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>