Scientists at University of Michigan Medical School think they may be on to finally answering questions such as what makes a person bipolar and why does bipolar disorder run so strongly in families, even though no single gene is to blame?
The researchers report that they used skin from people with bipolar disorder to derive the first-ever stem cell lines specific to the condition. In a new paper (“Transcripts involved in calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients”) in Translational Psychiatry, they describe 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 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. It's the first time scientists have directly measured differences in brain cell formation and function between people with bipolar disorder and those without.
Using induced pluripotent stem cells (iPSCs), the team exposed them to carefully controlled conditions and coaxed them to turn into stem cells that held the potential to become any type of cell, including neurons
“We have examined changes in gene expression as iPSCs derived from well-characterized patients differentiate into neurons; there was little difference in the transcriptome of iPSCs, but BP [bipolar] neurons were significantly different than controls in their transcriptional profile,” wrote the investigators. “Expression of transcripts for membrane-bound receptors and ion channels was significantly increased in BP-derived neurons compared with controls, and we found that lithium pretreatment of BP neurons significantly altered their calcium transient and wave amplitude. The expression of transcription factors involved in the specification of telencephalic neuronal identity was also altered.”
“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, Ph.D., the 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,” added Melvin McInnis, M.D., principal investigator of the Prechter Bipolar Research Fund and its programs. “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.”