24 — Microglia emerge as central players in brain disease

Today’s review paper looks at microglia, non-neuron cells in the brain that take on some of the roles of the immune-system. (Because the brain is usually protected by the blood-brain-barrier, the regular immune system cannot access brain tissue in the same way as it can access the rest of the body.)

Microglia appear to be responsible for many functions of the central nervous system (CNS): In particular, they form a structural lattice that seems to guide neuron development, and they also seem to respond to a wide variety of both inflammatory and noninflammatory damage-control responses. When a brain is developing, microglia prune less-active synapses; when a brain is developed, microglia are important for maintaining chemical homeostasis.

Microglia are also important in the healthy apoptotic process: When a cell self-destructs, it undergoes a complex process in which it marks itself for consumption by glia. If this self-marking fails, the cell is left as dangerous residue in the brain. (This is a gross oversimplification of the process, but hopefully not to the point of inaccuracy. If you want to read more about it, the Wikipedia page on nervous apoptosis is particularly well-written.) Synaptic plasticity — the ability to change synapse location and weight — is also heavily reliant on the presence of microglia.

Microglia counts and genetics are also seemingly altered in Autism spectrum disorders (though it’s not known if this is a cause or an effect), and it’s widely accepted that deficiencies in neuroinflammation are characteristic of Alzheimer’s, Parkinson’s, ALS, or dementia brains. Of the many gene mutations associated (please don’t tell Dr. Hendry that I almost used the word “implicated” in real life) with Alzheimer’s, many of them are seemingly only expressed in microglia, which suggests that the roles of microglia in Alzheimer’s and other diseases are much more important than have been appreciated before.