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If neurons are the brain’s rock stars, then glia are its supporting cast. Although neurons are the only brain cells that can transmit electrical signals, glia maintain energy homeostasis via glycogen storage and regulation (Dienel & Carlson, 2019) and are intimately involved in the production and regulation of two essential neurotransmitters: GABA and glutamate (Hertz & Rothman, 2016). Oligodendrocytes produce myelin: the protective sheaths around neuron axons that allows electrical signals to travel quickly and efficiently (Harry and Pont-Lezica, 2014). Although glia can’t communicate electrically, they can transmit chemical signals, which neurologist Peter Sterling points out is the most energy efficient method of short distance signal transmission (Sterling & Laughlin, 2017). Given its limited storage space, energy efficiency is the brain’s mantra.

Microglia have been described as the brain’s macrophages: involved in the inflammatory response to pathological conditions such as stroke, ischemia and neurodegenerative diseases (Sierra & Tremblay, 2014). Although research on microglia dates back almost 100 years, was not until recently that researchers were able to observe these tiny cells in their native state, thanks to the advent of two-photon laser microscopy (Davalos & Fuhrman, 2014). This relatively new imaging capability has revolutionized the way scientists understand the roles of microglia, particularly under physiologic conditions.

Throughout the lifespan, microglia are the brain’s sentries and housekeepers, surveilling their territory, and contributing to synaptic plasticity which in turn affects learning and memory, both in neonates and adulthood (Sierra & Tremblay, 2014). Microglia have a unique origin: they are the only brain cells whose precursors derive from the embryonic yolk sac. They invade the brain during embryonic development (Sierra & Tremblay, 2014), and once in residence, are self-sustaining throughout the lifespan.

Microglia assume two forms: the so-called “ramified” state in the healthy brain, and amoeboid state in disease (Watters & Pocock, 2014). The former term is descriptive, in that microglia in the healthy brain have processes that extend out from the cell body which resemble ram’s horns. These processes are constantly moving and interacting with other cells (Tremblay et al., 2014). In their ramified state, microglia migrate throughout their respective territories, ‘keeping house’ by removing debris created during synaptic pruning as well as dead cells.

As mentioned above, microglia also interact with the immune system, in both the periphery and the CNS. They are the sentries that send emergency signals following peripheral nerve injury, and also initiate the inflammatory cascade following acute injury or in degenerative conditions within the brain itself. Despite their tiny size, one could argue that microglia are the brain’s true rock stars: keeping vigilant watch throughout the lifespan and ensuring that the body’s most essential organ maintains its integrity. As with all good parents, microglia never rest, and they do so without complaint.

References

Davalos, D. & Furhman, M. (2014). Lessons from in vivo imaging. In M. Tremblay & A. Sierra (Eds.), Microglia in Health and Disease (pp. 81-114), Springer Science. http://www.springer.com

Dienel, G. & Carlson, G. (2019). Major advances in brain glycogen research: understanding the roles of glycogen have evolved from emergency fuel reserve to dynamic, regulated participant in diverse brain functions. In M. DiNuzzo & A. Schousboe (Eds.). Brain Glycogen Metabolism (pp. 1-16), Springer Science. http://www.springer.com

Harry, G. & Pont-Lezica, L. (2014). Developmental vascularization, neurogenesis, myelination and astrogliogenesis. In In M. Tremblay & A. Sierra (Eds.), Microglia in Health and Disease (pp. 193-222), Springer Science. http://www.springer.com

Hertz, L. & Rothman, D. (2016). Glucose, lactate, beta-hydroxybutyrate, acetate, GABA and succinate as substrates for synthesis of glutamate and GABA in the glutamine-glutamate/GABA cycle. In A. Schousboe & U. Sonnewald (Eds.), The Glutamate/GABA-Glutamine Cycle (pp. 9-42),Springer Science. http://www.springer.com

Sierra, A. & Tremblay, M (2014). Introduction. In M. Tremblay & A. Sierra (Eds.), Microglia in Health and Disease (pp. 3-6), Springer Science. http://www.springer.com

Sierra, A. & Tremblay, M. (2014). Adult neurogenesis, learning and memory. In In M. Tremblay & A. Sierra (Eds.), Microglia in Health and Disease (pp. 249-272), Springer Science. http://www.springer.com

Sterling, P. & Laughlin, S. (2017). Principles of Neural Design. MIT Press. http://www.mitpress.mit.edu

Tremblay, M. et al. (2014). Developing and mature synapses. In M. Tremblay & A. Sierra (Eds.), Microglia in Health and Disease (pp. 223-248), Springer Science. http://www.springer.com

Watters, J. & Pocock, J. (2014). Lessons from in vivo imaging. In In M. Tremblay & A. Sierra (Eds.), Microglia in Health and Disease (pp. 81-114), Springer Science. http://www.springer.com