Scientists discovered a new role for immune cells
called microglia in the developing brain. The
finding may reveal insights into neurodevelopmental
disorders like autism and schizophrenia.
Microglia serve as a primary defense against
infection and disease in the central nervous system.
In the adult brain, microglia survey the environment,
hunting for infectious agents or injured cells. When
they detect damage or pathogens, microglia become
activated and change shape in order to engulf and
eat their targets. They rapidly clear away dying
cells and repair tissue damage.
Microglial cells are also found in the brain’s
cerebral cortex during prenatal development, but
their role wasn’t well understood.
To investigate, a research team led by Dr. Stephen
Noctor at the University of California, Davis,
studied microglia in the developing brain tissue of
fetal rats, monkeys and humans. The work, funded in
part by NIH’s National Institute of Mental Health (NIMH),
appeared in the March 6, 2013, issue of the Journal
of Neuroscience.
During prenatal development, neural precursor cells—cells
with the ability to generate neurons—are rapidly
produced in well-defined regions of the brain called
proliferative zones. By labeling neural precursor
cells and microglia with specific antibodies and
other markers, Noctor and his colleagues were able
to track them using confocal microscopy.
To their surprise, the scientists found that
microglia were engulfing healthy precursor cells in
developing brain tissue. Microglia were colonizing
proliferative zones and the vast majority of them
(over 95%) were activated. Time-lapse images showed
microglia contacting healthy neural precursor cells
and eating them within a few hours.
The researchers speculated that microglial activity
during brain development might affect the number of
neural precursor cells. To explore this idea, they
used bacterial lipopolysaccharide (LPS)—a toxin that
activates microglia—and the antibiotic doxycycline (Dox),
which inhibits microglial activation.
The brain tissue of LPS-treated rat pups showed
reductions in the number of neural precursor cells
of as much as 40% compared to untreated rats. The
brain tissue of Dox-treated pups, on the other hand,
showed an increase of 20% compared to controls.
Finally, the researchers tested a chemical that
selectively kills microglia to see what effect it
would have on neural precursor cells. The treatment
removed 90% of microglia from the developing brain
and significantly increased the neural precursor
cell population.
Noctor proposes that the reason microglia feast on
neural precursor cells may be to prune brain size
during development. “It’s kind of like putting
breaks on the system; it’s as if the brain is saying
we have enough cells, we don’t need any more and the
microglia come in and wipe up the remaining
precursor cells,” he says.
Past studies have linked infections and immune
activation during pregnancy with neurodevelopmental
disorders such as schizophrenia and autism. Future
research will explore whether the process this study
uncovered could play a role.
For more information
National Institutes of Health (NIH)
(MDN)
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