Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists uncover nuclear process in the brain that may affect disease

18.08.2015

NIH-funded study highlights the possible role of glial brain cells in neurological disorders

Every brain cell has a nucleus, or a central command station. Scientists have shown that the passage of molecules through the nucleus of a star-shaped brain cell, called an astrocyte, may play a critical role in health and disease. The study, published in the journal Nature Neuroscience, was partially funded by the National Institutes of Health (NIH).


Scientists discovered that nuclear pores in astrocytes may play important roles in the brain.

Courtesy of Akassoglou lab, Gladstone Institute

"Unexpectedly we may have discovered a hidden pathway to understanding how astrocytes respond to injury and control brain processes. The pathway may be common to many brain diseases and we're just starting to follow it," said Katerina Akassoglou, Ph.D., a senior investigator at the Gladstone Institute for Neurological Disease, a professor of neurology at the University of California, San Francisco, and a senior author of the study.

Some neurological disorders are associated with higher than normal brain levels of the growth factor TGF-beta, including Alzheimer's disease and brain injury. Previous studies found that after brain injury, astrocytes produce greater amounts of p75 neurotrophin receptor (p75NTR), a protein that helps cells detect growth factors. The cells also react to TGF-beta by changing their shapes and secreting proteins that alter neuronal activity.

Dr. Akassoglou's lab showed that eliminating the p75NTR gene prevented hydrocephalus in mice genetically engineered to have astrocytes that produce higher levels of TGF-beta. Hydrocephalus is a disorder that fills the brain with excess cerebral spinal fluid. Eliminating the p75NTR gene also prevented astrocytes in the brains of the mice from forming scars after injuries and restored gamma oscillations, which are patterns of neuronal activity associated with learning and memory.

The cell nucleus is a ball of chromosomes wrapped in a protective fatty membrane. In this study, the researchers discovered that treating astrocytes with TGF-beta freed a small piece of the p75NTR protein to bind to nucleoporins, a group of proteins that regulates the passage of molecules in and out of the nucleus. Their results suggest that binding enhances the flow of certain critical molecules into the nucleus and enables astrocytes to enter a reactive state.

"This research highlights the importance of the nuclear pore complex in the brain and raises the possibility that it may be a target for treating a wide range of neurological disorders," said Jill Morris, Ph.D., program director at the NIH's National Institute of Neurological Disorders and Stroke (NINDS).

The scientists used high-resolution microscopes to watch the astrocyte nucleus in action. Nuclear pores that did not have the p75NTR gene were slightly larger than normal. When the scientists treated astrocytes with TGF-beta, they saw p75NTR proteins bind to nucleoporins and open the pores. This allowed transport into the nucleus of a protein called Smad2, which is essential for TGF-beta to exert its effects on astrocytes. In other experiments, the scientists showed that eliminating p75NTR from astrocytes blocked the transport of Smad2 into the nucleus.

"Nuclear pores are gatekeepers and p75NTR appears to be the key to unlocking particular gates," said Dr. Akassoglou. "We discovered novel roles for both players and will continue to study how the nuclear pore complex controls neuronal development and disease."

###

This work was supported by grants from NIH (NS051470, NS052189, NS066361, NS082976, AG047313, GM103412, RR004050), European Commission (FP7 PIRG08-GA-2010-276989), German Research Foundation (SCHA 1442/3-2), US National Multiple Sclerosis Society, American Heart Association, German Academic Exchange Service.

References:

Schachtrup et al. "Nuclear pore complex remodeling by p75NTR cleavage controls TGF-β signaling and astrocyte functions," Nature Neuroscience, June 29, 2015. DOI: 10.1038/nn.4054

For more information, visit: http://www.ninds.nih.gov

NINDS is the nation's leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institute on Aging: The NIA leads the federal government effort conducting and supporting research on aging and the health and well-being of older people. It provides information on age-related cognitive change and neurodegenerative disease specifically at its Alzheimer's Disease Education and Referral (ADEAR) Center at http://www.nia.nih.gov/Alzheimers. Information on health and on aging generally can be found at http://www.nia.nih.gov.

The National Institute of General Medical Sciences (NIGMS) supports basic research that increases understanding of biological processes and lays the foundation for advances in disease diagnosis, treatment and prevention. NIGMS-funded scientists investigate how living systems work at a range of levels, from molecules and cells to tissues, whole organisms and populations. The Institute also supports research in certain clinical areas, primarily those that affect multiple organ systems. To assure the vitality and continued productivity of the research enterprise, NIGMS provides leadership in training the next generation of scientists, in enhancing the diversity of the scientific workforce, and in developing research capacities throughout the country. More information about NIGMS can be found at http://www.nigms.nih.gov/Pages/default.aspx.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

Media Contact

Christopher G. Thomas
nindspressteam@ninds.nih.gov
301-496-5751

 @NINDSnews

http://www.ninds.nih.gov 

Christopher G. Thomas | EurekAlert!

More articles from Health and Medicine:

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

nachricht Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Health and Medicine >>>

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

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>