干细胞研究有助确定精神分裂症的源头

New University at Buffalo ¹ research demonstrates how defects in an important neurological pathway in early development may be responsible for the onset ² 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（妊娠期的） brain changes cause behavioral problems later in life -- just like the human disease., ,The genomic pathway, called the Integrative Nuclear FGFR 1 Signaling (INFS), is a central intersection ³ point for multiple pathways of as many as 160 different genes ⁵ believed to be involved in the disorder ⁶., ,"We believe this is the first model that explains schizophrenia（精神分裂症） 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 ⁸ mutation ⁷ that causes the disorder?" asks Stachowiak. "It's possible because INFS integrates diverse neurological signals that control the development of embryonic ⁹ stem cell and neural ¹⁰ progenitor ¹¹ 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 ¹² or mutation in a single schizophrenia-linked gene ⁴, 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 ¹³ in schizophrenia bind ¹⁴ the FGFR1 (fibroblast growth factor receptor) protein, which in turn, has a cascading ¹⁵ effect on the entire INFS., ,"We believe that FGFR1 is the conductor that physically ¹⁶ interacts with all genes that affect schizophrenia," he says. "We think that schizophrenia occurs when there is a malfunction ¹⁷ in the transition from stem cell to neuron, particularly with dopamine neurons."