of the Max - MDC

What are the physiological features of microglial
cells in brain tissue?
Microglial cells are the pathologic sensors and represent the
immune cells of the central nervous system. During any kind
of disease or any pathological event such as after trauma,
stroke or in multiple sclerosis, the resting microglial cell
transforms into an activated form characterized by an ameboid
morphology. Activated microglia can proliferate,
migrate to the site of injury, phagocytose, and release a
variety of factors like cytokines, chemokines, nitric oxide
and growth factors. They also express a variety of receptors
for chemokines and cytokines as expected from a
macrophage-like cell. We have addressed the question as to
whether microglia would also express receptors to sense
neuronal activity. We have recently developed an in situ
model which allows us to study the physiological responses
of resting and activated microglia. This enables us to characterize
the functional receptors and the physiological phenotype
of microglia in situ. Using this approach, we could
identify microglial receptors for GABA, the major inhibitory
transmitter of the CNS. Activation of the GABA B receptors
suppressed indicators of microglial activation such as the
release of IL-6. A similar reduction in proinflammatory
mediators was found with activation of purinergic receptors
and of adrenergic receptors.
Microglia expresses a variety of purinergic receptors and the
expression pattern undergoes changes during development
and in pathology. We have found an interesting interplay
between purinergic and adenosine receptors to control
microglial migration. In the extracellular space, ATP is rapidly
degraded to ADP, AMP and adenosine. In the brain, two
prominent ectonucleotidases, cd39 (NTPDase1) degrading
ATP to AMP and cd73 (5`-nucleotidase) degrading AMP into
adenosine, are exclusively expressed by microglial cells and
even have served as microglial-specific markers. We found
that ATP fails to migration in microglia deficient for cd39.
Function and Dysfunction of the Nervous System 161