Excessive trimming of the brains connections may underlie schizophrenia

Your brain is a complex and intricate network of connections that is constantly fine tuned through learning. In order to fine tune this delicate system, your body prunes neurons and connections that are no longer required so that it can get faster. This process is similar to uninstalling software from your computer that you no longer use in order to free up space and make it faster. When you are born, each neuron in your brain has around 2,500 connections to other neurons, by the time you are two this number increases to 15,000 per neuron. Some of these connections become stronger as you learn to talk, walk, recognize faces, and read but some of them become weaker and unnecessary. When you are adult, you have about half as many connections per neuron as a two-year-old child making your brain more efficient. The process of pruning is tightly controlled by specialized cells in your brain called microglia but new research suggests that when pruning goes overboard, schizophrenia may be the result.

Schizophrenia is a severe mental disorder that usually starts in young adults aged 16-30 and is characterized by hallucinations, delusions, loss of pleasure in life, and problems with memory. There is no known cause of schizophrenia but theories have included genetics, environmental exposures (substance abuse), or a problem in early childhood development. The researchers out of Boston, publishing in Nature, were studying variations in a gene called compliment component 4 (or C4), a gene that in the past has been associated with a risk of developing schizophrenia. They noticed that mice who lacked the gene to make the C4 protein didn’t undergo pruning in their brain that is normal during development. They also saw that this protein, in normal mice, attached to the neurons in the brain and seemed to target them for destruction. The conclusion from the paper was that too much, or overactive C4 could cause excessive pruning in the brain that results in short circuiting and possibly the symptoms of schizophrenia. It is known that people with schizophrenia who died had fewer synapses (the connections between neurons) in their brains so the idea seems plausible. This protein, C4, is more commonly thought to be important in helping your body kill bacteria, however it appears to have a dual ability in the body. Already there are drugs being tested in certain types of blindness to stop C4 from working so it is possible that these drugs could be important in treating schizophrenia in the future. Since this drug would need to be implemented before the excessive pruning takes place, we need to do more work to figure out which people are at risk of schizophrenia in order to treat before the disease sets in. Still, very exciting and hopeful research. Perhaps this research may help other diseases like autism where research suggests that pruning may be ineffective altogether.


Photo Credit: David Ensor


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