In our stem cell research, under the direction of K. Sue O’Shea, Ph.D., we are establishing induced pluripotent stem (iPS) cell lines from individuals with bipolar disorder and control individuals. Since living brain cells from individuals with bipolar disorder are not available for study, the goal of this study is to compare the characteristics of neurons from individuals with bipolar disorder with those from undiagnosed controls to understand the molecular mechanisms involved in bipolar disorder.
Using the very latest laboratory techniques, researchers isolate skin cells (fibroblasts) from a skin biopsy sample and manipulate, or “induce,” the cells to make them behave and function like stem cells derived from an early embryo. Once cell lines are established, we then coax the stem cells to form neurons similar to those in the brain. These cells will be grown in culture dishes to study how the cells may be affected by factors such as different medications, which could influence the functioning of the neuronal cells. Comparison of the results of cell culture studies with the extensive clinical and physiological data from study participants will help us determine why some individuals respond to specific interventions, or why stressors can affect behavior.
Effects of ECT on bipolar and control brain cells
Electroconvulsive therapy (ECT) is a medical intervention most commonly used in patients with severe major depression who have not responded to other treatments or who are at risk for suicide. ECT involves a brief electrical stimulation of the brain while the patient is under anesthesia. ECT produces substantial improvement in approximately 80 percent of patients.
However, we do not presently know how ECT works. One hypothesis is that the treatment helps brain cells remove toxic proteins from the brain cells that change the function of cells by damaging them.
In this research, we are exposing stem cell-derived brain cells from control individuals and bipolar disorder patients to a series of electroshocks. We then determine what proteins are released by the cells. We will then test if their release can be stimulated with medicines, rather than ECT.
Our lab has already established that astrocytes (a type of support cell in the nervous system) from control patients produce more exosomes (the sacs that transport toxic material out of the cell). We’ve also seen that the quantity and type of materials — proteins and RNA (Ribonucleic acid) — which are removed by exosomes are different in astrocytes from people with bipolar disorder.
We are currently studying the exosomes released passively (without shock) into the culture medium. Next, we will use an electroshock apparatus to apply current to the cells and compare the contents of exosomes released from bipolar and control cells. Finally, we will chemically activate and block this pathway and examine effects on neuronal behavior.
“We hope that research done in our lab will help us understand what changes in the brains of bipolar individuals, so that we can target better treatments to that process. Stem cells are important models, since there is no way to study living brain cells from patients with bipolar disorder.”
— K. Sue O’Shea, Ph.D.