19 December, 2000. Two immune proteins found in the brains of mice help the brain
develop and may play key roles in triggering developmental disorders like dyslexia
and neurodegenerative disorders like Parkinson's disease, according to a Harvard
Medical School study reported in [the 15 December issue of] Science.

Although neuroscientists have recently found evidence that the brain is subject
to immune surveillance, the Harvard researchers were surprised to discover the
mouse brain also produces its own immune molecules, the proteins Class I MHC
and CD3-zeta. In the immune system, the two proteins act as part of a lock and
key system to recognize and rid the body of foreign invaders. In the brain,
they may be part of a signaling system that recognizes and eliminates inappropriate
neural connections.

"What we find surprising and important about the results is that we found a
novel use by neurons for molecules previously thought only to be the domain
of the immune system," said Carla Shatz, Nathan Marsh Pusey professor of neurobiology
at HMS and lead author of the study. "What are these immune molecules doing
in the brain? The results of the studies imply they are being used by neurons
to accomplish the normal business of neurons during development and synaptic
 plasticity."

While the brain's early neural connections are determined by genetic instructions,
the refashioning that occurs during development-and in learning-is a product
of both genes and the brain's own activity. The research by Shatz and her team
suggests the two immune proteins play a role in the activity-dependent remodeling
of the brain. The immune proteins have been found not only in the hippocampus,
the region of the brain associated with learning, and the lateral geniculate
nucleus, the visual area of the brain, but also in many other regions of the
brain in mice.

The researchers found that mutant mice lacking either of the two immune proteins
failed to undergo normal development in the geniculate nucleus. Normally, projections
from the eye form a small tidy patch in the region, but in the mutants, the
connections created a larger and fuzzier profile, presumably because cells in
the area lacked the molecular mechanism for getting rid of the unneeded connections.
"We think Class I MHC acts like an anti-glue," said Shatz. The mutant mice also
experienced abnormal functioning in the hippocampus, the region of the brain
associated with learning. In normal mice, production of Class I MHC is especially
high in primary sensory areas of the brain-those areas that are thought to
function abnormally in people with dyslexia. Further studies are expected to
show if the mutant mice also have problems processing sensory information.

Though the evidence is still preliminary, the research could help clarify the
neurobiological dimensions of dyslexia. Preliminary studies by British researchers
of families with dyslexia suggest that some of them carry genetic defects on
chromosome 6-in the same region of the chromosome that carries the Class
I MHC genes. "It's very speculative at this point, but it remains certainly
a possibility that this could in some way be related to their dyslexia," Shatz
 said.

The widespread presence of MHC Class I in the brain prompts another speculation:
that neurodegenerative diseases such as Parkinson's and multiple sclerosis may
be the result of a misguided attack by immune cells on Class I MHC-bearing neurons.
"The idea that neurons would normally be expressing Class I MHC might help explain
why certain neurons die or are attacked," Shatz said. "MHC Class I-bearing neurons
could be the target for an abnormal immune response. I think that people need
to start thinking about that." (From Science press release.)

Reference:

Huh GS, Boulanger LM, Du H, Riquelme PA, Brotz TM, Shatz CJ. Functional requirement for class I MHC in CNS development and plasticity. Science. 2000 Dec 15;290(5499):2155-9. Abstract

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References

Paper Citations

  1. . Functional requirement for class I MHC in CNS development and plasticity. Science. 2000 Dec 15;290(5499):2155-9. PubMed.

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Papers

  1. . Functional requirement for class I MHC in CNS development and plasticity. Science. 2000 Dec 15;290(5499):2155-9. PubMed.

Primary Papers

  1. . Functional requirement for class I MHC in CNS development and plasticity. Science. 2000 Dec 15;290(5499):2155-9. PubMed.