Microglia: The Brain's First Responders

Abstract

New knowledge about microglia is so fresh that it's not even in the textbooks yet. Microglia are cells that help guide brain development and serve as its immune system helpers by gobbling up diseased or damaged cells and discarding cellular debris. Our authors believe that microglia might hold the key to understanding not just normal brain development, but also what causes Alzheimer's disease, Huntington's disease, autism, schizophrenia, and other intractable brain disorders.

Figure 1

Microglia in the mature, healthy brain exhibit small cell bodies and multiple long, thin processes (arms) that they use to constantly scan and survey their local environments within brain tissue. Photo credit S. Bilbo.

Figure 2

Microglia dynamically interact with synaptic elements in the healthy brain. Two-photon imaging in the olfactory bulb of adult mice shows processes of CX3CR1-GFP-positive microglia connecting to tdTomato-labeled neurons. Reprinted with permission from Jenelle Wallace at Harvard University (Hong and Stevens, 201620).

Figure 3

Synaptically coupled (i.e. communicating) neurons are under constant surveillance by glial cells, including microglia. If a neuronal synapse becomes “tagged” with complement protein C3, microglia recognize the tag with their C3 receptor (CR3/CD11b). This signal tells the microglia to engulf, or phagocytosis, and degrade the synapse. After microglial synaptic pruning, the eliminated synapse changes the way neurons communicate. Adapted from Lacagnina et al., 2017.

Figure 4. Microglia States in Health and Disease

Microglia have complex roles that are both beneficial and detrimental to disease pathogenesis including engulfing or degrading toxic proteins (i.e., amyloid plaques) and promoting neurotoxicity through excessive inflammatory cytokine release. Aberrations in microglia’s normal homeostatic functions (Surveillance, synaptic pruning and plasticity) may also contribute to excessive synapse loss and cognitive dysfunction in AD and other diseases. Salter and Stevens 2016 with permission.