Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Brain synapse formation linked to proteins

11.02.2005


Critical connections that neurons form in the brain during development turn out to rely on common but overlooked cells, called glia. These cells were known to support the neurons in adults, but had never been fingered as players in forming the connections between neurons, known as synapses.



The Stanford University School of Medicine researchers who conducted the work, led by Ben Barres, MD, PhD, professor of neurobiology, also discovered two of the proteins made by glial cells that signal synapse formation. This study, published in the Feb. 11 issue of Cell, could help researchers understand diseases such as epilepsy and addiction in which too many synapses form.

"We knew glia had a close relationship with neurons," Barres said. "We never thought the synapses would entirely fail to form without the glia." In fact, that relationship was considered so unlikely that the grant application was turned down six times because the work was considered too risky. The research was eventually funded by the National Institute on Drug Abuse, whose interest in the work stems from the possibility that new synapses are what keep recovered addicts craving drugs.


Barres said the relationship remained hidden in past research because of the neuron’s complete dependence on glial cells for survival in a lab dish. Nobody had ever succeeded in maintaining neurons without glial cells, so little was known about what the glial cells did, exactly.

However, in past work, Barres and his team devised a way of keeping the neurons alive without glial cells. In this environment the neurons formed one-seventh the number of synapses compared to cells grown with glia. He added that the glia probably have many additional roles, also unknown. "Ninety percent of human brain cells are glia and it’s completely a mystery what they do," he said.

These previous experiments simply showed that the proteins glia secrete help neurons in a lab dish form synapses. What wasn’t clear is which proteins, exactly, are responsible for the new synapses and whether glia perform the same role in the developing brain. The Cell paper addressed these questions.

Barres and his team found that when they added various glial proteins to neurons grown in a lab dish without glia, only two proteins, called thrombospondins, encouraged new synapses to form. However, the synapses aren’t completely normal. The synapse is made from two neurons-one that sends the message and one that receives the message. On the sending side, the synapse appears normal, but the receiving end isn’t able to detect signals. Barres said other as yet unidentified signals from glia are necessary to form fully functional synapses.

When the group created mice that lacked the two thrombospondins they found 40 percent fewer synapses on average than the normal counterparts.

These thrombospondins’ role of encouraging synapses to form makes sense, given when they are present in the brain: Barres and his group found them in the brains of developing mice during the time that the brain is actively making new synapses.

Interestingly, recent studies have found that one of the two thrombospondins is found at far higher levels in adult human brains than in adult monkey brains, possibly suggesting a key difference in the two animals’ ability to form new synapses.

Barres said the thrombospondins they studied are just two of five related proteins. So far it hasn’t been possible to eliminate all five thrombospondins in mice, but he suspects what few synapses the mice eked out were thanks to the remaining thrombospondins or perhaps other glial proteins. "Had we been able to knock out all five we might have seen even more synapse loss," Barres said.

Figuring out how and why new synapses form could be a boon for doctors treating people with brain damage. "If we deliver thrombospondins in the adult brain we could potentially turn on synapse formation," Barres said.

People with epilepsy face the opposite problem. In this disease, the area of the brain where the epileptic attack originates contains both a mass of glial cells and neurons with excessive synapses. Barres suggested that the glial scar might have originally triggered the additional synapses to form. Learning more about how glia trigger synapse formation could help prevent the disabling condition.

Co-first authors on this paper were Karen Christopherson, PhD, postdoctoral fellow, and Erik Ullian, PhD, a postdoctoral fellow now at UCSF. Other Stanford researchers who contributed to this work are undergraduate students Caleb Stokes and Christine Mullowney.

Amy Adams | EurekAlert!
Further information:
http://www.stanford.edu

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>