Stem cell research helps find origins of schizophrenia

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.

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

The UB findings, published in Schizophrenia Research, test the hypothesis in a new mouse model of schizophrenia that demonstrates how gestational brain changes cause behavioral problems later in lifejust 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, professor in the Department of Pathology and Anatomical Sciences, 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. Its 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 doesnt 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. Thats 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.

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Stem cell research helps find origins of schizophrenia