Researchers believe they may have identified the potential cause of pediatric (or childhood-onset) schizophrenia, linking the serious mental disorder to the lack of development of certain cells in the brain. The team transplanted brain cells from people with the condition into young mice and observed that their nerve cell network didn’t develop properly.
The research, published in the journal Cell, focused on glial cells in the brain, which help hold neurons in places, deliver nutrients to neurons, and assist in the synaptic connections between nerve cells. It appears that the glial cells of people who suffer from childhood-onset schizophrenia were highly dysfunctional and weren’t able to perform their functions.
"The findings of this study argue that glial cell dysfunction may be the basis of childhood-onset schizophrenia," lead researcher Dr Steve Goldman, a neurologist at the University of Rochester Medical Center (URMC), said in a statement. "The inability of these cells to do their job, which is to help nerve cells build and maintain healthy and effective communication networks, appears to be a primary contributor to the disease."
The team extracted skin cells from individuals with pediatric schizophrenia and turned those cells into induced pluripotent stem cells, which have the ability to turn into any type of cell. The researchers forced them to develop into glial progenitor cells (GPCs), which are the “parent” cells for two kinds of glia – astrocytes and oligodendrocytes. The former are support cells, while the latter produce myelin – a fatty substance that acts as an insulator for neurons.
These GPCs were transplanted into the brains of neonatal mice and out-competed the mice's own GPCs. Mice that received the faulty cells developed schizophrenic-type symptoms and behaviors. An analysis of their brain structure showed that the development of astrocytes and oligodendrocytes was delayed, causing signaling between neurons to become severely impaired.
"The astrocytes didn't fully mature and their fibers did not fill out their normal domains, meaning that while they provided control to some synapses, others had no coverage," first author Dr Martha Windrem, from URMC's Center for Translational Neuromedicine, added. "As a result, the neural networks in the animals became desynchronized and uncoordinated."
The research could lead to new therapies. Schizophrenia is a condition previously observed only in humans, so this approach provides a way to have an animal model to test new medicines and therapies on. The knowledge that glial cells might play a significant role could lead to treatments that target them specifically.