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Day 209: Know your spinal cord – Microglia

macrophage eating a bactria

We cover this in the post, but it’s so cool I had to use it for the featured image.

It’s day fifty-one of knowing your spinal cord! For those of you who just found us, fear not we have all these posts in reverse chronological order listed in our neuroanatomy category. For everyone else, lately we’ve been talking about glial cells. This came about from the post on glial scarring which made me realize we should probably define glia. There are four types of glial cells found in the spinal cord (that we know of) we’ve covered three of them already and today we are talking about the last kind, the microglia.

While all the other glial cells got cool names, microglia got stuck with micro (small) and glia, the name of the group. While the name may start as micro-, they are macro, macrophage cells that is, making them part of the immune system. Below is a drawing of what microglia look like and an outline of its function. Microglia account for 10–15% of all cells found within the brain, that’s a lot of cells. Now like all the types of cell in the glial family they have multiple roles, but first let’s talk about what a macrophage is since that is the primary function.

Classical and alternative activation of microglia

M1/M2 polarization of microglia. Classical activation is induced by pro-inflammatory cytokines and secrete pro-inflammatory cytokines. M1 microglia favor the neuroinflammatory and oxidant state, which can lead to neuronal damage and death. Alternative activation of the microglia increase the expression of the mannose receptor (CD206), and secrete anti-inflammatory cytokines (TGF-b) and neurotrophic factors, among others. Microglia M2 exert a repairing/ remodeling and neuroprotective function. DOI:  10.1089/ars.2017.7099

Macrophage (greek for “big eaters”) are exactly as the name suggests, they eat things. The macrophage are a type of white blood cell, that engulfs and digests cellular debris, foreign substances, microbes, and anything else that does not have the type of proteins specific to healthy body cells on its surface. The process is as cool as you might imagine (if you’re a bio nerd like I am anyway). Below is an animation showing a macrophage hunting down and eating a bacteria (tiny pair of black dots). The large circles are your red blood cells and the macrophage actually follows the bacteria and eats it.

macrophage eating a bactria

So now that we’ve geeked out over that. Let’s talk about why microglia are needed (aside from the animation above). In addition to being very sensitive to small changes in their environment, each microglial cell also physically surveys its domain on a regular basis. This action is carried out in the ameboid and resting states (image below highlighting the process). While moving through its set region, if the microglial cell finds any foreign material, damaged cells, apoptotic cells (cells going through programed cell death), neurofibrillary tangles (hyperphosphorylated tau protein, commonly known as a marker for alzheimer’s), DNA fragments, or plaques it will activate and phagocytose (consume) the material or cell.

microglial activation steps

In this manner microglial cells also act as “housekeepers”, cleaning up random cellular debris. During developmental wiring of the brain, microglial cells play a large role regulating numbers of neural precursor cells and removing apoptotic neurons. There is also evidence that microglia can refine synaptic circuitry by engulfing and eliminating synapses. This was first seen in spinal lesions in 1968 Post development, the majority of dead or apoptotic cells are found in the cerebral cortex and the subcortical white matter. This may explain why the majority of ameboid microglial cells are found within the “fountains of microglia” in the cerebral cortex.

Recent research verified, that microglial processes constantly monitor neuronal functions through specialized somatic junctions, and sense the “well-being” of nerve cells. Via this intercellular communication pathway, microglia are capable of exerting robust neuroprotective effects, contributing significantly to repair after damage. Which brings us to the idea that microglia (like all of the glial cells we’ve looked at) have an important role in the regeneration of damaged tissues. For example, the image below shows activation of the microglia in the spinal cord after damage (left side of the cord).

activated microglial cells in damaged L4 segment of spinal cord

Activation of microglia in L4 spinal cord segment following nerve injury. Epifluorescence image of L4 spinal cord segment following nerve injury. Left half side in the image represents the nerve injured side. DOI: 
10.1186/1744-8069-4-15

As with the last three glial cell types, we have to include a small disclaimer that this is just a small slice of the complex life of the microglia and its responsibilities in the spinal cord and brain. We could dedicate a whole blog to any one of these glial cell types in particular and we would probably still miss key features or functions. However, this should give you a good introduction to the microglia and some of the key functions it has. When we talk about using biology to repair spinal cord damage, more than likely it will involve, in part, glial cells. This concludes our introduction to glial cell types, so we hope that our previous post on glial scarring makes more sense now.

What’s next? Not sure, but as always, we’ll think of something.

Until next time, don’t stop learning! 

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