Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stem Cell Research Helps to Identify Origins of Schizophrenia

23.01.2013
UB scientists propose first genomic explanation for disease

New University at Buffalo research demonstrates how defects in an important neurological pathway in early development may be responsible for the onset of schizophrenia later in life.


Arrows point to cell nuclei in human embryonic stem cells in which a fibroblast growth factor receptor protein, (FGFR1), targets diverse genes implicated in schizophrenia.

The UB findings, published in Schizophrenia Research (paper at http://bit.ly/Wq1i41), test the hypothesis in a new mouse model of schizophrenia that demonstrates how gestational brain changes cause behavioral problems later in life – just like the human disease.

Partial funding for the research came from New York Stem Cell Science (NYSTEM).

The genomic pathway, called the Integrative Nuclear FGFR 1 Signaling (INFS), is a central intersection point for multiple pathways of as many as 160 different genes believed to be involved in the disorder.

“We believe this is the first model that explains schizophrenia from genes to development to brain structure and finally to behavior,” says lead author Michal Stachowiak, PhD, professor in the Department of Pathology and Anatomical Sciences in the UB School of Medicine and Biomedical Sciences. He also is director of the Stem Cell Engraftment & In Vivo Analysis Facility at the Western New York Stem Cell Culture and Analysis Center at UB.

A key challenge with the disease is that patients with schizophrenia exhibit mutations in different genes, he says.

“How is it possible to have 100 patients with schizophrenia and each one has a different genetic mutation that causes the disorder?” asks Stachowiak. “It’s possible because INFS integrates diverse neurological signals that control the development of embryonic stem cell and neural progenitor cells, and links pathways involving schizophrenia-linked genes.

“INFS functions like the conductor of an orchestra,” explains Stachowiak. “It doesn’t matter which musician is playing the wrong note, it brings down the conductor and the whole orchestra. With INFS, we propose that when there is an alteration or mutation in a single schizophrenia-linked gene, the INFS system that controls development of the whole brain becomes untuned. That’s how schizophrenia develops.”

Using embryonic stem cells, Stachowiak and colleagues at UB and other institutions found that some of the genes implicated in schizophrenia bind the FGFR1 (fibroblast growth factor receptor) protein, which in turn, has a cascading effect on the entire INFS.

“We believe that FGFR1 is the conductor that physically interacts with all genes that affect schizophrenia,” he says. “We think that schizophrenia occurs when there is a malfunction in the transition from stem cell to neuron, particularly with dopamine neurons.”

The researchers tested their hypothesis by creating an FGFR1 mutation in mice, which produced the hallmarks of the human disease: altered brain anatomy, behavioral impacts and overloaded sensory processes.

“By attacking the INFS pathway, we were able to produce schizophrenia in mice,” he says.

He adds that if such a generalized genomic pathway is causing the disease, then it should be possible to treat the disease with a more generalized approach. “We may even be able to devise ways to arrest development of the disease before it presents fully in adolescence or adulthood,” he says.

The UB work adds to existing evidence that nicotinic agonists, often prescribed as smoking cessation drugs, could help improve cognitive function in schizophrenics by acting on the INFS. Schizophrenics smoke at a dramatically higher rate than the general population, long believed to be a form of self-medication.

In addition to NYSTEM, funding for the research was provided by UB and the March of Dimes and Birth Defects.

UB co-authors with Stachowiak are: his graduate students, S. Narla, D. Prokop, C. Syposs, C. Terranova, A. Kucinski and R. Curl; research assistant professors B. Birkaya, PhD, E. K. Stachowiak, PhD, all in the Department of Pathology and Anatomical Sciences; S. Wersinger, PhD, assistant professor, and Y. Yang of the Department of Psychology; A. Parikh, doctoral candidate and E.S. Tzanakakis, PhD, associate professor of the Department of Chemical and Biological Engineering in the School of Engineering and Applied Sciences and the Western New York Stem Cell Culture and Analysis Center at UB.

Other co-authors are I. Klejbor of Gdansk Medical University, M. Bencherif of Targacept Inc. and T. Corso of Lake Erie College of Osteopathic Medicine.

Media Contact Information
Ellen Goldbaum
Senior Editor, Medicine, Public Health
Tel: 716-645-4605
goldbaum@buffalo.edu
Twitter: @egoldbaum

Ellen Goldbaum | EurekAlert!
Further information:
http://www.buffalo.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>