Scientists have for the first time directly measured differences in brain cell formation and function between people with bipolar disorder and those without.
Scientists from the University of Michigan Medical School used skin from people with bipolar disorder to derive the first-ever stem cell lines specific to the condition.
In a new paper in the journal Translational Psychiatry, researchers described how they transformed the stem cells into neurons, similar to those found in the brain – and compared them to cells derived from people without bipolar disorder.
The comparison revealed very specific differences in how these neurons behave and communicate with each other, and identified striking differences in how the neurons respond to lithium, the most common treatment for bipolar disorder.
The team used a type of stem cell called induced pluripotent stem cells, or iPSCs.
By taking small samples of skin cells and exposing them to carefully controlled conditions, the team coaxed them to turn into stem cells that held the potential to become any type of cell. With further coaxing, the cells became neurons.
“This gives us a model that we can use to examine how cells behave as they develop into neurons. Already, we see that cells from people with bipolar disorder are different in how often they express certain genes, how they differentiate into neurons, how they communicate, and how they respond to lithium,” said Sue O’Shea, a U-M stem cell specialist who co-led the work.
“We’re very excited about these findings. But we’re only just beginning to understand what we can do with these cells to help answer the many unanswered questions in bipolar disorder’s origins and treatment,” said Melvin McInnis, principal investigator of the Prechter Bipolar Research Fund and its programmes. “For instance, we can now envision being able to test new drug candidates in these cells, to screen possible medications proactively instead of having to discover them fortuitously,” McInnis said.
In the study, when the team measured gene expression first in the stem cells, and then re-evaluated the cells once they had become neurons, very specific differences emerged between the cells derived from bipolar disorder patients and those without the condition.
Specifically, the bipolar neurons expressed more genes for membrane receptors and ion channels than non-bipolar cells, particularly those receptors and channels involved in the sending and receiving of calcium signals between cells. Calcium signals are already known to be crucial to neuron development and function.
The findings support the idea that genetic differences expressed early during brain development may have a lot to do with the development of bipolar disorder symptoms – and other mental health conditions that arise later in life.
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