During brain development, the brain is a frenzy of activity: new brain cells (neurons) are born, migrate to where they need to go, and eventually form connections with other neurons. Subtle problems with any of these steps can change the brain’s wiring diagram, and contribute to risk for developing schizophrenia and other psychiatric diseases.
A study published online May 13th in Molecular Psychiatry links an abnormality in the birth of neurons to schizophrenia and bipolar disorder. Led by Li-Huei Tsai of the Massachusetts Institute of Technology, the study focused on the workings of ANK3, a gene implicated in both bipolar disorder and schizophrenia. Loss of ANK3, the researchers report, elevated the number of newborn neurons in the embryonic mouse brain.
This abnormal production of cells could be traced to a signaling pathway involved in brain development (and, interestingly, cancer—a disease of abnormal cell production). The researchers, including three NARSAD Grantees, Tracey L. Petryshen, Ph.D. (2014 NARSAD Independent Investigator Grantee), Karun K. Singh, Ph.D. (2013 NARSAD Young Investigator Grantee) and Pamela B. Sklar, M.D., Ph.D. (1995, 1998, 2006 NARSAD Grantee), could restore normal levels of neuron birth by boosting levels of another member of this pathway, called glycogen synthase kinase 3 (GSK3β).
The findings uncover a new role for ANK3, which encodes a protein better known for getting the channels essential for electrical signaling in the right places along the axon, which carries information between neurons. The new results suggest that ANK3 can fine-tune the number of new neurons born, and that perhaps producing too many or too few brain cells can contribute to risk for developing schizophrenia or bipolar disorder.