In a paper published online September 13th in Stem Cell Reports, Foundation 2013 NARSAD Distinguished Investigator Grantee Vivian Hook, Ph.D., and colleagues at the Salk Institute in La Jolla, California, report that they have discovered a way to stimulate neurons that are derived from human induced pluripotent stem cells (hiPSCs)—from the skin cells of patients with schizophrenia—to release neurotransmitters. Neurotransmitters are chemicals that excite or inhibit the transmission of electrical signals through the brain and are crucial for brain function. The research team reports that hiPSC-derived neurons from the patients with schizophrenia (as compared with those of healthy control subjects) secreted higher amounts of three neurotransmitters (dopamine, norepinephrine and epinephrine) that are broadly implicated in a range of psychiatric disorders.

“All behavior has a neurochemical basis in the brain,” says Dr. Hook. “This study shows that it is possible to look at precise chemical changes in neurons of people with schizophrenia.”

Proof-of-principle studies of hiPSCs in schizophrenia research have been trickling out mainly from two groups—those of NARSAD Independent Investigator Grantees Guo-Li Ming, M.D., and Hongjun Song, Ph.D., at Johns Hopkins University and the group led by 2013 NARSAD Distinguished Investigator Grantee and Foundation Scientific Council Member Fred “Rusty” Gage, Ph.D., at the Salk Institute, along with former colleague, 2012 NARSAD Young Investigator Grantee Kristin Brennand, Ph.D., now at the Icahn School of Medicine at Mt. Sinai in New York. In this study, Drs. Hook, Gage and colleagues created stem cells and then neurons in culture dishes using skin cells from three people with schizophrenia and compared them with three control subjects.

By discovering a simple method for stimulating hiPSCs to release neurotransmitters, the researchers have made an important step forward in this technique. The approach allows scientists to observe and stimulate human neurons in ways impossible in animal models or human subjects. “The significance of this study is that patient-derived stem cell neurons can uncover previously unknown neurotransmitter brain mechanisms occurring in schizophrenia,” explains Dr. Hook. “Because in vivo human brain research is limited, hiPSC neurons derived from patients create new opportunities to understand changes in brain cells occurring in nervous system disorders. These approaches can potentially define new drug targets for the development of therapeutic agents to improve the lives of schizophrenia patients.”

This study adds credibility as well as findings to build upon, to an area that researchers believe holds a great deal of promise for understanding how mental illnesses develop and for developing more effective treatments.



Read the abstract for this research paper.

Read more about this research in the Schizophrenia Research Forum.

Read the press release.