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.
|Contact: Ellen Goldbaum|
University at Buffalo