Better drugs to treat bipolar disorder (BP) are lacking, in part because there have been no living brain cells to study to understand its cellular origins. New research has made it possible to obtain stem cells from patient skin cells. Then, those stem cells are coaxed into forming living brain cells for scientific study. The O’Shea lab used this technique to form astrocytes called glial cells (a type of non-neuron brain cell that protects and supports neuronal cells). One way that glial cells perform their supportive role is by releasing packets of growth factors (exosomes) that are taken up by neurons (Figure 1).
The O’Shea Lab is optimistic about new findings from several recent studies in which they have investigated the effects of exosomes on brain function. In the first, they obtained exosomes from the culture medium of BP and Control (C) astrocytes and added them to brain cells as illustrated in the diagram of a tissue culture dish (Figure 2).
STUDY 1. (Figure 2) The lab found that untreated C neurons (A1 left) had more electrical connections than untreated BP neurons (B1). If C exosomes were added to BP neurons (B2), the BP neurons were healthier and had more connections, while adding exosomes from BP astrocytes to C neurons (A3) damaged the control neurons. This strongly suggests that BP astrocytes may produce toxic factors while C astrocytes produce protective factors.
STUDY 2. Finally, to begin to identify the specific factor(s) responsible for the differences between the C and BP exosomes, the lab collected BP and C exosomes and studied what proteins were in each sample. 399 different proteins were identified. Many of the distinguishing proteins were found to be associated with psychiatric disorders. Additionally, some of the proteins are known to be associated with cellular communication and movement. Finally, several proteins connected to neurodevelopmental and neurodegenerative diseases were identified in the BP samples.
Overall, this work indicates that:
- Exosomes derived from C astrocytes contain factors that promote neuronal development and function.
- Exosomes derived from BP astrocytes contain factors that impair neuronal function and development.
- The lab now has several valid tests to identify specific proteins that may cause these effects.
In the coming year, the lab will investigate the blood of individuals who gave skin samples to obtain the iPSC brain cells to see if the same proteins are present. If so, the proteins could serve as early markers of bipolar disorder, helping with diagnosis and earlier treatment interventions.
The O’Shea lab is open now — please don’t hesitate to call and arrange a visit!