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Microglia In Focus

Contributed by Kris Kralovich, M.Sc.

Microglia are specialized type of glial cells. Glia (or neuroglia) are structural, non-neuronal cells that support neurons in the brain and central nervous system (CNS). Microglia are derived from primitive macrophages in the embryonic yolk sac and account for up to 10-15% of all cells in the brain.

During development, microglia have a similar appearance to macrophages, and later undergo differentiation in phases as signals are received from the maturing CNS around them. Mature resting microglia have a unique, highly branched morphology, and have processes known as ramifications (these ramifications are useful to distinguish microglia from macrophages). Ramifications play a role in sensing changes in homeostasis. When a change is detected, microglia convert to an “activated” phenotype (which is more spheroid and less densely branched) allowing the cell to respond in a variety of ways.

Microglia perform an exhaustive list of functions to maintain homeostasis in the brain and CNS. Ramifications scan the extracellular space and communicate with other cell types, including neurons, astrocytes and endothelial cells.

Microglia release trophic factors to support the formation of neuronal circuits. The release of other trophic factors by microglia can result in programmed cell death in normal brain development. Microglia further aid in the “clean up” of cell death via phagocytosis. This phagocytic activity also functions to allow plasticity in neurons (learning-dependent synapse formation), the elimination of defective synapses and of course in the event of bacterial or virial infection. Microglia also respond to other types of damage, including stroke, tumor and injury.

How are microglia able to execute so many different functions? Through an extensive and complex network of highly regulated signaling pathways. Here are some examples of the pathways involved:

- Pattern recognition receptor (PRR) signaling
- Cytokine receptor signaling
- Chemokine receptor signaling
- Neurotransmitter receptor signaling
- TREM2 receptor signaling
- Phosphatidylserine receptor signaling
- Scavenger receptor signaling
- Fc receptor signaling
- Siglec-3 receptor signaling

In order to study all of these responses, activated microglia are often categorized into two groups: “classically activated,” or M1, which results in a proinflammatory response and is characterized by the production of cytokines, and “alternatively activated,” or M2, which focus on tissue repair and debris clearance. These different types of responses each have signature shifts in protein expression.

Microglia Markers

To date, very few specific markers have been identified specific to microglia, as some markers are common to other related cell types (monocytes). Further complicating the issue is that markers can be up or downregulated depending on the state of the cell. It is important to keep these issues in mind when staining.

Microglial Iba1/AIF1, TMEM119 and TREM2 antibodies coming soon!

Aves Labs, PhosphoSolutions, and Antibodies Incorporated have been hard at work developing antibodies against the microglial markers Iba1/AIF1 and TMEM119 in addition to the microglial protein TREM2. Sign up below to our email list to get notified of these product releases and promos, and check back soon for updates!

Iba1/AIF1 Antibodies
- Chicken anti-Iba1 (Aves Labs)
- Rabbit anti-Iba1 (PhosphoSolutions)

TREM2 Antibodies
- Chicken anti-TREM2 (Aves Labs)
- Rabbit anti-TREM2 (PhosphoSolutions)

TMEM119 Antibody
- Mouse monoclonal anti-TMEM119 (NeuroMab/Antibodies Incorporated)

References

Wolf S, Boddeke HWGM, Kettenmann H. Microglia in Physiology and Disease. Annual Review of Physiology. Volume 79 2017. pp619-643. 10.1146/annurev-physiol-022516-034406

Nayak D, Roth TL, McGavern DB. Microglia Development and Function. Annual Review of Immunology. 2014 32:367-402. 10.1146/annurev-immunol-032713-120240

Ayman E, Rivest S. Microglia Ontology and Signaling. Front Cell Dev Biol. 2016; 4. 72. 10.3389/fcell.2016.00072

Greter M, Lelios I, Croxford AL, Microglia Versus Myeloid Cell Nomenclature during Brain Inflammation. Front Immunol. 2015; 6: 249. 10.3389/fimmu.2015.00249

Lenz K, Nelson LH. Microglia and Beyond. Innate Immune Cells as Regulators of Brain Development and Behavioral Function Front Immunol. 2018; 9: 698. 10.3389/fimmu.2018.00698

Zhu C, Kros JM, van der Weiden M, Zheng PP, Cheng C, Mustafa DAM. Expression site of P2RY12 in Residential Microglial Cells in Astrocytomas Correlates with M1 and M2 Marker Expression and Tumor Grade. Acta Neuropathologica Communications V5, 4 2017. 10.1186/s40478-016-0405-5

Benett ML, Bennett C, Liddelow SA, Bahareh A, Zamanian JL, Fernhoff NB, Mulinyawe SB, Bohlen CJ, Adil A, Tucker A, Weissman IL, Chang EF, Li G, Grant GA, Hayden Gephart MG, Barres BA. New Tools for Studying Microglia in the Mouse and Human CNS. 10.1073/pnas.1525528113