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“Nanny” Cell Malfunctions May Contribute to Schizophrenia By Hugh Brady

A research team led by Dr. Steven Goldman at the University of Copenhagen may have uncovered some important clues about how schizophrenia develops.  Schizophrenia has many causes and may, in fact, actually be several different diseases with overlapping symptoms.  Goldman’s research looks at a set of causes different from what most research considers.  Up until now, most research into schizophrenia has looked at defects in the neurons, the nerve cells that transmit messages to one another.  But Goldman’s research looks at glial cells.

Glial cells are the support system for the neurons, and more than half of the brain’s mass is made up of these glial cells.  Oftentimes a neuron is attended by 6 or 8 glial cells.  One article calls them “nanny cells” because they support an nurture the neurons. 

 Glial cells come in two types, oligodendrocytes and astrocytes:  

  • Oligodendrocytes help create the myelin sheaths that insulate and protect the axons and dendrites that extend from the central body of the neuron and connect to other neurons. 

  • Astrocytes function in the synapses, the junctions between neurons, and help regulate the neurotransmitters that carry the nerve signals across the synapses.

Together the glial cells allow the neurons to, as one summary of the research puts it, “do what they do best – transmit messages.”

In the developing human embryo a particular type of stem cell, the progenitor cell, gives rise to the glial cells.  Researchers suspected that a genetic defect in the creation of the progenitor cells may lead to defective glial cells, which in turn harm the functioning of some neurons and  so gives rise to the malfunctions that characterize schizophrenia.  In other words, malfunctioning glial cells lead to miscommunication between neurons and hence to schizophrenia.  

It is often difficult to experiment on human brains – people do, after all, like to keep their brains intact.  And mice, often the subjects of medical experiments, have brains and other systems that don’t function exactly as human brains and systems do.  That is part of the reason new disease treatments that work wonderfully in mice often fail in human tests.

So Goldman and his team came up with an amazing way to experiment on mice; the modified mouse brains to more closely resemble human brains.  Of course they remain mouse-sized brains, but they mimic more of the chemistry and cell functions of actual human brains.

Goldman’s team devised a way to seed mouse brains with progenitor cells from people living which schizophrenia.  As the defective progenitor cells spread through the mouse brains, the mice developed symptoms very similar to some of the symptoms of schizophrenia, including severe anxiety, anti-social behavior and sleep problems.  No way to tell, of course, if the mice were hearing voices or suffering from delusions.  

The team then compared the results to mice whose brains had been seeded with progenitor cells from people without a mental illness.  The mice receiving these progenitor cells behaved normally. 

Glial cells are nerve cells that constitute the brain’s supportive tissue in the central nervous system and the peripheral nervous system. Glial cells constitute the largest group of nerve cells and their volume accounts for more than half of the human brain with 9-10 glial cells for each nerve cell. image is for illustrative purposes only. Credit: OpenStax.

Neuroscientists have long believed that as the human brain matures, to goes through a process known as selective pruning in which redundant and unused neurons are discarded or pruned.  One of the biggest prunings takes place in late adolescence just about the same time as schizophrenia begins to show itself.  It is thought that errors in the pruning process lead to excess pruning and to the Illness.  Goldman’s research team believes that errors in the progenitor cells may lead to abnormalities in the glial cells, and without the proper support of the glial cells, some of the resulting underperforming neurons atrophy.  The body then sees them as excess and prunes them away.  

Several genes that lead to the creation of progenitor cells have been identified and may point the way to the development of medications that can insure that the progenitor cells function correctly.  

Goldman’s team thinks that continued research in this area may lead to the ability to infuse the brains of people with schizophrenia with properly functioning progenitor cells which could then create properly functioning glial cells and possibly repair the damage done by the illness.  

Dr. Goldman noted, ““It was through studies of mice with human glial cells that we succeeded in testing how dysfunctional glial cells may cause abnormalities in the formation of the brain’s neural networks, which may in turn cause severe anxiety, anti-social behavior and severe sleep problems. We see these problems in the mice, just as in human patients. This is an important discovery because it will now enable us to develop methods that can counteract the unwanted development of progenitor cells “

Amazing, isn’t it?

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Matt Husar