Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mad cow protein aids creation of brain cells

14.02.2006


Few conditions are more detrimental to human brains than the one popularly referred to as mad cow disease. But now there’s reason to suspect that the protein which, when malformed, causes bovine spongiform encephalopathy in cows and Creutzfeldt-Jakob disease in people, might also be necessary for healthy brain function. Researchers from Whitehead Institute for Biomedical Research and Harvard Medical School/Massachusetts General Hospital have discovered that the normal form of this detrimental protein may actually help the brain create neurons, those electricity-conducting cells that make cognition possible.



"It’s been difficult to understand why this prion protein, which when malformed subjects us to this horrible disease, is so abundant in our brains in the first place," says Whitehead Member Susan Lindquist, who is also a professor of biology at MIT. Along with Jeffrey Macklis of Harvard Medical School and Massachusetts General Hospital, she is co-senior author on this Proceedings of the National Academy of Sciences paper, scheduled to be published the week of February 13. "We’ve known for years what happens when this protein goes wrong. Now we’re starting to see what its normal form does right."

For over ten years, researchers have known that a protein called PrP causes mad cow disease and its human equivalent, Creutzfeld-Jakob disease, when it forms incorrectly. PrP is a prion, a class of proteins that has the unusual ability to recruit other proteins to change their shape. (PrP is shorthand for "prion protein".) This is significant, because a protein’s form determines its function. When a prion changes shape, or "misfolds," it creates a cascade where neighboring proteins all assume that particular conformation. In some organisms, such as yeast cells, this process can be harmless or even beneficial. But in mammals, it can lead to the fatal brain lesions that characterize diseases such as Creutzfeld-Jakob.


Curiously, however, PrP can be found throughout healthy human bodies, particularly in the brain. In fact, it’s found in many mammalian species, and only on the rarest occasions does it misfold and cause disease. Clearly, scientists have reasoned, such a widely conserved protein also must play a beneficial role.

In 1993, scientists created a line of mice in which the gene that codes for PrP was knocked out, preventing the mice from expressing the prion in any tissues. Surprisingly, the mice showed no sign of any ill effect. The only difference between these mice and the control mice was that the knock-out animals were incapable of contracting prion-related neurodegenerative disease when infected. Researchers knew then that PrP was necessary for mad-cow type diseases; any other kind of normal function remained unknown.

Recently, researchers from the labs of Lindquist and Whitehead Member Harvey Lodish discovered that PrP helps preserve stem cells in the blood. Because of this, Lindquist teamed up with Macklis to see if there might also be a similar connection between PrP and cells in the brain, where the prion protein is far more abundant.

Andrew Steele, a graduate student from the Lindquist lab, teamed up with Jason Emsley and Hande Ozdinler, postdoctoral researchers in the Macklis lab, to investigate the effects PrP might have on neurogenesis. (Neurogenesis is the process by which the brain creates new neurons in the developing embryonic brain and, to a limited extent, even in the adult brain.) To do this they studied embryonic brain tissue from three kinds of mice: those in which the PrP gene was permanently disabled, or knocked out; those in which the gene was over-expressed, producing an unusually large amount of PrP; and normal control mice.

Steele and Emsley isolated neural precursor cells--early stage cells that give rise to mature neurons and so-called glial support cells. (These precursor cells are often referred to as neural stem cells, though they lack certain properties that are characteristic of broader stem cells.) After placing these embryonic precursor cells under culture conditions that enabled them to grow and differentiate, they noticed striking differences. Cells from the knock-out mouse remained in the precursor stage for a long time, compared to the control mice. But cells in which PrP was over-expressed began forming mature neurons almost immediately.

"The more PrP you have, the faster you become a neuron. The less you have, the longer you’ll stay in a precursor state," says Steele.

In addition, the researchers discovered that in adult mouse brains, PrP is only expressed in neurons, but not in the glial cells, cells that form the brain’s connective tissue. They also found that while the amount of PrP does affect the speed with which neurons were produced in the adult brain, ultimately the different mice ended up with the same number of neurons. In order to further investigate these findings, the researchers are currently placing these different groups of mice in stimulation-rich environments that will require the quick production of new neurons. The idea is to observe the mice and see if there are any significant differences in how they perform and behave.

"We now see that the normal form of this prion protein is one of many key players in the fascinating and important process of neurogenesis," says Macklis, who is also a member of the Harvard Stem Cell Institute.

David Cameron | EurekAlert!
Further information:
http://www.wi.mit.edu

More articles from Life Sciences:

nachricht At last, butterflies get a bigger, better evolutionary tree
16.02.2018 | Florida Museum of Natural History

nachricht New treatment strategies for chronic kidney disease from the animal kingdom
16.02.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

Im Focus: Autonomous 3D scanner supports individual manufacturing processes

Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).

Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Fingerprints of quantum entanglement

16.02.2018 | Information Technology

'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers

16.02.2018 | Health and Medicine

Hubble sees Neptune's mysterious shrinking storm

16.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>