MHC immune molecule and synapse density in brain

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Immune Molecule Regulates Brain Connections

ScienceDaily (Feb. 28, 2011) ? The number of connections between nerve

cells in the brain can be regulated by an immune system molecule,

according to a new study from UC . The research, published Feb. 27

in the journal /Nature Neuroscience/, reveals a potential link between

immunity, infectious disease and conditions such as schizophrenia or autism.

Schizophrenia, autism and other disorders are associated with changes in

connectivity in the brain, said Kimberley McAllister, associate

professor in the Center for Neuroscience and Departments of Neurology

and Neurobiology, Physiology and Behavior at UC . Those changes

affect the ability of the brain 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, " McAllister said.

The study does not show a direct link between immune responses and

autism, but rather reveals a molecular pathway through which a

peripheral immune response or particular genetic profile could alter

early brain development, McAllister said.

The researchers looked at a protein called Major Histocompatibility

Complex type 1 (MHC type I). In both rodents and humans, these proteins

vary between individuals, and allow the immune system to distinguish

between 'self' and 'non-self.' They play a role, for example, in

rejecting transplanted organs and in defending against cancer and virus

infections.

In this and another recently published study, McAllister's group found

that MHC type I molecules are present on young brain cells during early

postnatal development. To test their function, they 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. They found that when

the density of these molecules on the surface of a brain cell goes up,

the number of connections, or synapses, it has with neighboring brain

cells goes down. The reverse was also true: decreased MHC expression

increased synaptic connections.

" The effect on synapse density was mediated through MHC type I

proteins, " McAllister said.

" 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,

the team found, and MHCI mediated 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 said.

The other coauthors on the paper were: former graduate student n

Glynn, graduate students Bradford Elmer and a Garay, researcher

Xiao-Bo Liu, postdoctoral researcher Leigh Needleman, and research

associate Faten El-Sabeawy.

Funding for the work was provided by grants from several foundations,

including Cure Autism Now, the Merck Fund, the March of Dimes, and

the National Alliance for Research on Schizophrenia and Depression; a

pilot grant from the UC MIND Institute, and the National Institute

for Neurological Disorders and Stroke.

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*Journal Reference*:

1. n W Glynn, Bradford M Elmer, a A Garay, Xiao-Bo Liu,

Leigh A Needleman, Faten El-Sabeawy & A Kimberley McAllister.

*MHCI negatively regulates synapse density during the

establishment of cortical connections*. /Nature Neuroscience/, 27

February 2011 DOI: 10.1038/nn.2764 <http://dx.doi.org/10.1038/nn.2764>