Protein oversees junctures in brain

UC DAVIS (US) — An immune system molecule is able to regulate the number of connections between nerve cells in the brain possibly altering early development.

The research, published in the journal Nature Neuroscience, points to a potential link between immunity, infectious disease, and conditions like schizophrenia or autism, that are associated with changes in the brain that affect its ability to process information correctly.

“Certain immune genes and immune dysregulation have also been associated with autism and schizophrenia, and the immune molecules that we study in brain development could be a pathway that contributes to that altered connectivity,” says Kimberley McAllister, associate professor of neuroscience and neurology at University of California, Davis.

The study does not show a direct link between immune responses and autism, but rather reveals a molecular pathway through which an immune response or particular genetic profile might alter early brain development, McAllister says.

The researchers looked at a protein called Major Histocompatibility Complex type 1 (MHC type I) that varies between individuals in both rodents and humans and allows the immune system to distinguish between “self” and “nonself.”

The protein plays a role, for example, in rejecting transplanted organs and in defending against cancer and viral infections.

In this and another recently published study, MHC type I molecules were found to be present on the surface of young brain cells during early postnatal development.

To test their function, researchers studied mice lacking MHC type I on the surface of neurons, as well as isolated neurons from mice and rats with altered levels of MHC type I.

When the density of the molecules on the surface of a brain cell goes up, the number of connections, or synapses, that it has with neighboring brain cells diminishes. The reverse was also true: decreased MHC expression increased synaptic connections.

“The effect on synapse density was mediated through MHC type I proteins,” McAllister says, “but these immune proteins don’t just regulate synapse density, they also determine the balance of excitation and inhibition on young neurons—a property critical for information processing and plasticity in young brains.”

Expression of MHCI on neurons was itself regulated by neural activity and MHCI affected the ability of neural activity to alter synaptic connections.

About 10 years ago, other researchers discovered that MHC type I is involved in elimination of connections during a critical period of late postnatal brain development.

“We have now found that there is another role for MHC type I in establishing connections during early postnatal development of the brain,” McAllister says.

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