Published February 11, 2013
New UB research shows how defects in an important neurological pathway in early development may be responsible for the onset of schizophrenia later in life.
The UB study explains how numerous genetic mutations can result in schizophrenia.
The researchers produced the disorder in mice by attacking a genomic pathway known as Integrative Nuclear FGFR 1 Signaling, or INFS.
A system that controls the development of the entire brain, the
INFS serves as a central intersection point for multiple pathways
of as many as 160 different genes implicated in
The researchers hypothesize that the disorder develops when an alteration or mutation in a single schizophrenia-linked gene leads to a cascading effect, causing the INFS system to malfunction.
“We think that schizophrenia occurs when there is a malfunction in the transition from stem cell to neuron, particularly with dopamine neurons, says lead author Michal Stachowiak, PhD, professor of pathology and anatomical sciences.
The INFS pathway is key in this process because it integrates
diverse neurological signals that control the development of
embryonic stem cells and neural progenitor cells, he adds.
Stachowiak and his colleagues tested their hypothesis with embryonic stem cells. They found that some of the genes implicated in schizophrenia bind the fibroblast growth factor receptor protein. Significantly, this protein, FGFR1, is believed to interact with all genes that affect schizophrenia, says Stachowiak.
When the researchers created an FGFR1 mutation in mice, the animals had the hallmarks of the human disease: altered brain anatomy, behavioral impacts and overloaded sensory processes.
“We believe this is the first model that explains schizophrenia from genes to development to brain structure and, finally, to behavior,” says Stachowiak, who directs the Stem Cell Engraftment and In Vivo Analysis Facility at the Western New York Stem Cell Culture and Analysis Center (WNYSTEM).
If a generalized genomic pathway causes the disease, it should be possible to treat it with a more generalized approach, Stachowiak says.
“We may even be able to devise ways to arrest development
of the disease before it presents fully in adolescence or
adulthood,” he notes.
The UB research adds to existing evidence that nicotinic agonists, often prescribed as smoking cessation drugs, could help improve cognitive function in people with schizophrenia by acting on the INFS.
Long believed to be a form of self-medication, smoking is seen at much higher rates in people with schizophrenia than in the general population.
The multidisciplinary research team included UB co-authors from the Department of Pathology and Anatomical Sciences:
from the Department of Psychology:
from the Department of Chemical and Biological Engineering and WNYSTEM:
Additional coauthors are: