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.
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 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.
University at Buffalo: http://www.buffalo.edu
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Algorithms developed by Google designed to encode thoughts, could lead to computers with ‘common sense’ within a decade, says leading AI scientist
New fossil evidence suggests dogs emerged as a separate species from wolves far earlier than scientists previously believed
Researchers discover the 425-million-year-old remains of a new species of parasite - still clamped to the host animal it invaded.
It should be raptor egg blue instead of robin egg blue. Some modern birds lay colourful eggs, but now we know it's a trick their dinosaur ancestors used too
WASHINGTON (Reuters) - Scientists on Thursday unveiled the most comprehensive analysis ever undertaken of the world's ocean plankton, the tiny organisms that serve as food for marine creatures such as the blue whale, but also provide half the oxygen we breathe.
Scientists on Thursday unveiled the most comprehensive analysis ever undertaken of the world's ocean plankton, the tiny organisms that serve as food for marine creatures such as the blue whale, but also provide half the oxygen we breathe.
Researchers say they're excited about a new brain implant that allowed a paralyzed patient to control a robotic arm with his mind. Erik Sorto is the first in the world to have this new neural prosthetic device. Elaine Quijano reports.
Genetically, at least, not that much has changed in the billion years since you two last shared a relative. Roughly half the 500 genes yeast need for life are interchangeable with the human versions.
What controls aging? Biochemist Cynthia Kenyon has found a genetic mutation that can more than double the lifespan of a tiny worm, which points to how we might one day significantly extend human life.
Java sparrows amp up their tunes with acoustic beak taps synchronized with chirps