Scientists know that disorders such as autism, schizophrenia, epilepsy, and intellectual disability are the result of differences in the brain. New findings on how the brain is organized during early childhood could be a factor in these disorders, and offer scientists a platform for future research.
A newborn baby’s brain is not very organized. There are few pathways developed, so brain cells communicate with other brain cells in a haphazard, disorganized way. As the child develops, the brain begins to weed out pathways that are less efficient, and to solidify those that are useful. New research from the University of Michigan Medical School has found a key molecular mechanism that the brain uses to complete this process.
Hisashi Umemori, M.D., Phd, research assistant professor at U-M’s Molecular and Behavioral Neuroscience Institute and assistant professor of biological chemistry, explains,
“For the brain to be really functional, we need to keep the most active and efficient connections. So during development, it’s crucial to establish efficient connections, and to eliminate inactive ones. We have identified a key molecular mechanism that the brain uses to stabilize and maturate the most active connections.”
SIRP-Alpha is a protein that is found on the surface of various cells throughout the body. It helps normal cells tell the immune system not to attack, and previous research has shown that they are involved in a neuron’s ability to form a presynaptic nerve terminal, which is an extension of the cell that reaches out towards a neighboring cell and can send the chemical signals brain cells use to communicate with one another.
They found that when a brain cell receives signals from a neighboring cell across a synapse it releases SIRP-alpha into the space between the cells. Two molecules within the cell, CaMK and MMP, act like scissors that cut the SIRP-alpha protein in half so it can float to other cells. The SIRP-alpha protein attaches to a CD47 receptor on the other cell. When this binding occurs, a message is sent to the first cell indicating that the signal was received and that the synapse is a good one. The cell then sends more chemical signaling molecules into the synapse. The researchers believe that this process helps brain cells determine which synapses to keep and which to let wither away.
Umemori indicated that future research will look into what happens when the SIRP-alpha does not get cleaved as it should, and at what’s happening in cells when a synapse is eliminated.
“This step of shedding SIRP-alpha must be critical to developing a functioning neural network,” he says. “And if it’s not done well, diseases and disorders may result. Perhaps we can use this knowledge to treat diseases caused by defects in synapse formation.”
Disorders such as autism, schizophrenia, and epilepsy are complex, and affect the patient in a variety of ways. This study may pave the way for research that could lead to helpful treatments in the future.