For a century, the mechanisms that underlie the neuropsychiatric condition schizophrenia have elude scientists. It’s hard to understand the cellular and molecular abnormalities when you only have postmortem brain samples to work with.
But alas, using skin cells from schizophrenic patients, researchers have created schizophrenia in a dish!
"This is the first time that a complex mental disease has been modeled in live human cells,” says study leader Fred Gage of Salk Institute for Biological Studies.
Schizophrenia combines paranoid delusions, auditory hallucinations, and diminished cognitive function. It affects about 3 million people in the US, and now, researchers can look at live neurons from schizophrenia patients and screen for drugs that may reverse it.
"Nobody knows how much the environment contributes to the disease," explains Kristen Brennand of Salk. "By growing neurons in a dish, we can take the environment out of the equation, and start focusing on the underlying biological problems."
- The team took skin cells from 4 schizophrenic patients and reprogrammed those into stem cells, which differentiated into neurons (pictured).
- They saw that these neurons displayed some of the same types of cellular abnormalities seen in neurons from schizophrenic patients, including fewer connections between neurons and some altered gene expression.
- The researchers also performed an analysis of gene activity in the cells, and they identified nearly 600 genes that have activity different from cells taken from people without schizophrenia. Only about a quarter of these have been previously identified with postmortem tissue.
- The team also tested the brain cells with 5 antipsychotic drugs: clozapine, loxapine, olanzapine, risperidone and thioridazine. They discovered that only loxapine increased the neurons' ability to reach out and connect with their neighbors.
"For many years, mental illness has been thought of as a social or environmental disease, and many thought that if affected people just worked through their problems, they could overcome them," says Gage. "What we are showing are real biological dysfunctions in neurons that are independent of the environment."
The study was published in Nature last week, and it was partly funded by Sanofi-Aventis.
Image: Kristen Brennand / Salk Institute for Biological Studies