Foundation-Supported Research Advances Technology to Study Developmental Mechanisms of Schizophrenia

Kristen Brennand, Ph.D. - brain & behavior research expert on schizophrenia
Kristen Brennand, Ph.D.

A new study published online April 1st in Molecular Psychiatry by 2012 NARSAD Young Investigator Grantee Kristen Brennand, Ph.D., and 2013 NARSAD Distinguished Investigator Grantee, Fred Gage, Ph.D., offers researchers a quicker, easier way to study irregularities in brain cell development linked to schizophrenia and other brain disorders. Using stem cell technology, but rather than trying to convert skin cells to stem cells and then on to neurons, the researchers stopped at an intermediate stage of the process and produced what are called neural precursor cells (NPCs). The researchers report that many of these cells can be produced and that they are very similar in some respects to neurons.

The discovery several years ago that a patient’s skin cells could be converted into neurons by growing the cells under very specific conditions offered a breakthrough new technology to provide researchers with a supply of neurons, each with a particular patient’s exact genetic makeup. Coaxing the cells to become neurons, as scientists describe it, is an intricate and delicate process and has proven to be very labor intensive. This new, intermediate-step process offers a simpler, more rapid approach to studying the development of neurons.

In this new paper, Drs. Brennand, Gage (also a Foundation Scientific Council Member) and colleagues compare the intermediate cells generated from patients with schizophrenia to those from healthy controls. The researchers, including Foundation Scientific Council Member, Pasko Rakic, M.D., Ph.D., Director of the Yale Kavli Institute for Neuroscience at Yale University School of Medicine, and Kazue Hashimoto-Torii, Ph.D., 2013 NARSAD Young Investigator Grantee and Assistant Professor of Pediatrics at The George Washington University School of Medicine & Health Sciences, found that the cells from patients have abnormal levels of many proteins, altered abilities to migrate, and increased levels of cellular stress—all features that seem to be present in the brains of people with the illness.

The researchers report that stem cell-derived neurons most resemble fetal brain tissue and that this was also observed in the stem-cell induced NPCs. This implies that the study of stem cell-induced neurons and the new NPC model can offer important insight into disease predisposition rather than modeling late-stage illness.

Read more about this research on the Schizophrenia Research Forum.

Read the paper abstract.