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October 17, 2012--------News Archive Return to: News Alerts


Microglial cells have a small cell body with long tendrils that detect
signs of injury or disease within the nervous system. When activated,
microglia ingest bacteria, viruses, diseased or injured nerve cells.

WHO Child Growth Charts

       

Attack! Silent Watchmen Defend the Nervous System

In many processes within the nervous system, there is a common event - cells called microglia are activated from surveillant watchmen into fighters

Microglia are the immune cells of the nervous system, ingesting and destroying pathogens and damaged nerve cells. Until now little was known about the molecular mechanisms of microglia activation despite this being a critical process in the body.

However, new research from the Montreal Neurological Institute and Hospital – The Neuro - at McGill University provides the first evidence that mechanisms regulated by the Runx1 gene control the balance between the surveillant versus activated microglia states.

The finding, published in the Journal of Neuroscience, has significant implications for understanding and treating neurological conditions.

Microglia

As surveillant watchmen, microglial cells wait for something bad to happen in the nervous system. They have a small cell body and long branches that monitor the local environment. As soon as there are signs of injury or disease, microglia are activated into fighters.

The branches retract and the microglia morph into a large rounded body in order to attack and ingest pathogens: bacteria, viruses, and diseased or injured nerve cells (for example in head trauma).

If microglia activation is not precisely controlled, however, it can become harmful to the body as microglia can start to attack healthy cells. For example, after epileptic seizures, the brain responds by regenerating new nerve cells. The microglia help in this process of regeneration, but they can also negatively influence the survival of the new born nerve cells if their activation persists for too long.

The research team at The Neuro sought out the answers to important questions: How can we learn how the process of activating microglia from watchmen to fighter is controlled? What can we do to ensure that the beneficial effects of microglia activation predominate over their potentially deleterious effects?


It turns out that the process of activating microglia
in the adult brain is almost in reverse of mechanisms
that occur during fetal nervous system development.

Microglia in the developing fetal brain are in early
fighter mode, with the capacity to eliminate
cell debris and redundant nerve cell connections.
Pruning the nerve cell network is a normal
process during fetal development.

Soon after birth microglia are gradually deactivated
from fighters to surveillant watchmen,
a state they will maintain unless injury or trauma
to the adult brain causes them to revert back to fighters.


"So the approach we took was to study the normal process of microglia deactivation during brain development based on the premise that understanding this process might also help us understand adult brain microglia activation in response to injury or disease," says Dr. Stefano Stifani, lead investigator and neuroscientist at The Neuro.


"Our study provides evidence for a previously
unrecognized role of a particular gene – Runx1,
in promoting the transition of microglia from its'
early form of activated fighter
to surveillant watchmen

in the postnatal mouse brain.

We show that Runx1 is expressed in early fighter
microglia during the first two postnatal weeks
but that if Runx1 function in these cells is inhibited
the cells tend to persist longer and their transition
into watchmen microglia is delayed.


Dr. Stefano Stifani


We also looked at an experimental animal model in which an artificial injury causes surveillant microglia to be activated into fighters. This showed that Runx1 expression is induced in microglia when they become activated following injury in the adult mouse nervous system, suggesting that Runx1 might be important for controlling how long fighter microglia remain activated in the adult nervous system, as it does in the developing brain."

Dr. Stefano continues: "These findings improve our understanding of microglia biology in the developing and injured adult brain. Moreover, they have potential therapeutic implications for several neurological conditions - further research could lead to the development of treatment strategies by pharmacologically targeting key modulators of microglia activation."

About The Neuro
The Montreal Neurological Institute and Hospital — the Neuro, is a unique academic medical centre dedicated to neuroscience. Founded in 1934 by the renowned Dr. Wilder Penfield, the Neuro is recognized internationally for integrating research, compassionate patient care and advanced training, all key to advances in science and medicine. The Neuro is a research and teaching institute of McGill University and forms the basis for the Neuroscience Mission of the McGill University Health Centre. Neuro researchers are world leaders in cellular and molecular neuroscience, brain imaging, cognitive neuroscience and the study and treatment of epilepsy, multiple sclerosis and neuromuscular disorders. For more information, visit www.theneuro.com.

Original article: http://www.mni.mcgill.ca/media/stories/microglia/