I went to the Lab today and had a good discussion about the project I’ll be working on. We have neural progenitor cells (essentially neuronal stem cells) from the olfactory neuroepithelium of individuals with bipolar illness and matched controls (ONP cells). The cells from bipolar individuals have the genetic heritage of Bipolar d/o.These cells have been treated with MSG at a concentration of 1mM. The cells from Bipolar individuals apoptose (undergo programmed cell death) much more than from healthy controls. Now we are going to grow these cells in a 3 dimensional cell culture and determine epigenetic alterations specific to the illness. Epigenetic alterations are changes in a gene that do not involve changes in its sequence. These alterations are additions to the DNA sequence of the gene, such as:
1) Methylation (addition of a methyl = CH3 group),
2) Acetylation (addition of an Acetyl = O=C–CH3
3) As well as changes in Histones, which are proteins that bind the DNA tightly into chromosomes.
The theory is that Bipolar d/o is caused by epigenetic changes.
Also, I found out today about an article that came out on Oct. 14, by Dr. E. I. Ginns et al (http://www.nature.com/mp/journal/vaop/ncurrent/abs/mp2014118a.html) that says a gene, funnily enough named Sonic hedgehog (Shh) is protective against getting Bipolar d/o.
In her research among the Old Order Amish, which extends back more than 40 years, Janice A. Egeland, PhD, professor emerita of Psychiatry and Behavioral Sciences at UMMSM and co-author of the current study, found that both EvC (a form of dwarfism) and bipolar were prevalent in an extended family descended from the same progenitor. Both conditions clearly travelled together over the generations in a few families extending from this same pioneer. Yet no person with EvC was ever reported with bipolar disorder despite decades of research across multiple generations.
EvC dwarfism results from genetic mutations that disrupt the signaling pathway known as sonic hedgehog (Shh). Statistical analyses confirmed the significant negative association between EvC and bipolar disorder. This further suggested that the Shh pathway plays a role in bipolar disorder. The great thing about this is that drugs already in clinical trials for other medical conditions that target Shh protein signaling may have the potential to be better treatments for bipolar disorder.
Ginns cautioned that although “we have a good idea of potential novel drug target(s) that could stop symptoms, it’s still unclear what changes along the Shh pathway lead to bipolar disorder. The Shh pathway involves more than a dozen other molecules, and interacts with over 100 other genes. It’s likely that other genes or proteins in this pathway may participate in determining the various symptoms and sometimes catastrophic outcomes seen in patients with affective disorders, including suicide.”
Ginns and his collaborators are already working to unravel more details of the puzzle and identify changes in the Shh signaling and related pathways that correlate with disease symptoms. “Even though the symptoms of bipolar affective disorder can be quite varied and complicated, the underlying genetics might actually have a more simple cause than we could have imagined,” said Ginns.
All in all a very exciting day for people interested in Bipolar d/o and especially meaningful for me.