Scientists have discovered that defects in an important neurological pathway in early development may be responsible for the onset of schizophrenia later in life.
Scientists from the University at Buffalo, The State University of New York tested the hypothesis in a new mouse model of schizophrenia that demonstrated how gestational brain changes cause behavioural problems later in life - just like the human disease.
Schizophrenia is a mental disorder characterised by a breakdown of thought processes and common symptoms include auditory hallucinations, paranoid or bizarre delusions, or disorganised speech and thinking.
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 behaviour," said lead author Michal Stachowiak.
A key challenge with the disease is that patients with schizophrenia exhibit mutations in different genes, he said.
"How is it possible to have 100 patients with schizophrenia and each one has a different genetic mutation that causes the disorder?" asked 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," he said in a statement.
"INFS functions like the conductor of an orchestra. It doesn`t matter which musician is playing the wrong note, it brings down the conductor and the whole orchestra," he added.
"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," Stachowiak said.
Using embryonic stem cells, Stachowiak and colleagues 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 said.
"We think that schizophrenia occurs when there is a malfunction in the transition from stem cell to neuron, particularly with dopamine neurons," he added.
The researchers tested their hypothesis by creating an FGFR1 mutation in mice, which produced the hallmarks of the human disease: altered brain anatomy, behavioural impacts and overloaded sensory processes.
The study was published in Schizophrenia Research.
Photo courtesy: kristaylorfilmcerebral.blogspot.com