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The Fascinating Lives of Glial Cells and How They Can Help Treat Depression (for starters!)


Glial Cells make up 85-90% of the brain. Neurons make up the other 10-15%. What are Glial Cells capable of, and how do they affect your mental health and physiological wellbeing?


What is a Glial Cell?


There are six types of glial cells that operate in the Central Nervous System (CNS) and the Peripheral Nervous System (PNS). Each has a specific form and function that contributes uniquely to the balance of the entire system.


Glial, or Glia, comes from the Greek word for "Glue". This word refers to what researchers previously thought was the Glial Cell's only function: to act as the glue that holds neurons together. Now, however, we know they do so much more!


Glia are non-neuronal cells that scavenge the nervous system in search of damaged or dead cells, pathogens, and foreign substances, repairing and disposing of debris as they cast their web-like tentacles out over the biological landscape. Previously thought to remain in one area, we now know that Glial Cells have an almost limitless reach throughout the nervous system and are not confined to any particular lobe in the brain.


What Does Each Type of Glial Cell Do?


In the Central Nervous System, we have Oligodendrocytes, Astrocytes, Microglia, and Ependymal Cells. In the Peripheral Nervous System there are Satellite Cells and Schwann Cells.

The Central Nervous System Glial Family:


Making up the majority of the CNS family of Glial cells are the Oligodendrocytes. These cells wrap themselves like a cuff around the neuron's Axon (thinner than a strand of hair, the axon is a neuronal cable that enables the electrical impulses from neurons to travel to other neurons), acting as a super-efficient insulator for electrical pulses sent from the neuron. Without the insulation from this type of Glial Cell, the transmission would be much slower and more likely to dissipate when traveling from one cell to another. Multiple Sclerosis (MS) is an example of why the health and reliability of these cells is so important. When the Oligodendrocytes are damaged or not working efficiently, the communication between the cells, the brain, and the body become disrupted and can lead to several chronic symptoms, specifically those of MS.


Next, we have Astrocytes. The primary function of these star-shaped cells is to maintain the health and balance within the brain, including tending to and protecting neurons, recycling chemicals, and providing neurons with all the nutrition they need to function in top condition.


Microglia protect the brain's immune system. They scavenge and degrade dead cells and protect the brain from invading microorganisms.


Lastly, we have Ependymal cells. These cells line the ventricles (empty cavities) in the brain and have access to nearby blood vessels. They filter some of the materials out of the vessels and are involved in the production of cerebrospinal fluid, which serves as a cushion for the brain. They move the fluid between the spinal cord and the brain, and are a component of the choroid plexus (produces most of the cerebrospinal fluid (CSF) of the central nervous system).


Peripheral Nervous System Glial Family:


In the PNS family of Glial cells, we have Satellite Glia and Schwann Cells. Satellite Glia provide the necessary nutrients and structural support to neurons, while Schwann cells surround the entire axon to form the myelin sheath. The Myelin Sheath is a lipid-rich, fatty substance that insulates and increases the rate at which electrical impulses are passed along the axon. The duty of a Schwann cell in the PNS is comparable to the function of oligodendrocytes in the CNS.


Glial Cells and Mood/Neurological Disorders


Glial cells can influence lifespan, pain, sleep, mood, memory, and learning, and they are essential for healthy brain function.


Studies now show that mood disorders are associated with abnormalities in the glial cell population (Öngür, D., Bechtholt, A. J., et al. 2014). Disorders including depression and anxiety along with neurological disorders like Amyotrophic Lateral Sclerosis (ALS), Alzheimers Disease, Multiple Sclerosis (MS), Epilepsy, and even some brain cancers, all present with a level of Glial dysfunction. Since Glia are so essential to the minute functions of the brain starting at the level of direct communication between cells, it's understandable that when glial health is low, other areas of the brain and body will suffer accordingly.


When are Glial Cells at risk?


Any neurodegenerative disorder will affect the Glial cells as well as the neurons, and will naturally affect learning abilities and memory. Although different neurodegenerative diseases exhibit different symptoms, there are some underlying similarities such as the loss of neurons or myelin sheath in certain areas of the CNS, or the presence of protein aggregates either in the nuclei or in cytoplasm of the neurons (Sathyajith, D (2020).


Neuroinflammation and Chronically-Activated Glial Cells


Neuroinflammation can be a normal process in the acute phase after an injury, but when the inflammation becomes chronic due to prolonged injury or nervous system dysregulation, several neurodegenerative diseases and mood disorders can take place.

During the neuroinflammatory process, microglial cells are triggered to release proinflammatory mediators such as cytokines, matrix metalloproteinases (MMP), reactive oxygen species (ROS), and nitric oxide (NO) (Lee, E. J., Choi, M. J., et al. 2017). Extended periods of neuroinflammation are well-known markers for acute and chronic CNS disorders. A prolonged state of inflammation in the brain can lead to chronically activated astrocytes and microglial cells, which then continues the cycle and perpetuates the state of the inflammation.


The activated glia then continuously release a variety of neuroexcitatory substances that potentiate neurotransmission, especially proinflammatory cytokines (Lee, E. J., Choi, M. J., et al. 2017). When this root cause, or whatever initiated this cycle, of the inflammatory reaction in the brain remains unresolved, the glia cells continue to excite substances within the brain that turn what could otherwise be an acute inflammatory reaction into a chronic one.


Addressing The Root Cause of Inflammatory Responses - Relief to the Glia


Several emotional and physical experiences can trigger an inflammatory response in the brain. In reflecting upon the studies referenced above, one could gather that when such triggers are left unresolved or blocked, certain glia cells go to work and don't stop until the cause of the inflammation is resolved.


One website defines nervous system dysregulation as "a novel term to describe the clinical symptoms that result from repeated activation or extended conditions of stress on the nervous system" (Rajkowska, G., & Miguel-Hidalgo, J. J. (2007). Stress on the nervous system can translate to any kind of trauma to daily stress, or even the heightened levels of cortisone released in response to the curvature of the spine in individuals with scoliosis. Our bodies need a fine level of balance within the system to function well, and anything that raises our stress levels or triggers a chronic state of fight or flight can prolong neuroinflammation. Adverse Childhood Experiences (ACEs) are an example of early traumas that have been known to trigger many mood disorders due to the dysregulated state of the nervous system.


Regulating the nervous system can be achieved or worked toward in many ways and will depend greatly on the certified professional you are working with as well as the individual's specific situation and needs. Certified therapists or counselors with areas of specialty regarding co/self-regulation practices and recovering from traumas can be a good resource, for example, but the trauma could range from physical or nutritional, to emotional and/or energy-based, so the modality of healing and achieving or working toward regulation is usually a varied process. It could be helpful to explore your options, looking into professionals like holistic nutritionists and chiropractors to specialized therapists or energy healers, to start.


Glial Cells and Depression


Reductions in the density and number of glial cells are reported in fronto-limbic brain regions in major depression and bipolar disorders, while levels of a certain protein (glial fibrillary acidic protein - GFAP) and immunoreactive astrocytes are observed in the prefrontal cortex of younger individuals with depression (Rajkowska, G., & Miguel-Hidalgo, J. J. (2007). One study on Gliogenesis and Gliopathology in Depression hypothesizes that a deficit in atrocyte cells (which participate in uptake, metabolism, and recycling process of glutamate - an important neurotransmitter present in over 90% of all brain synapses in the Central Nervous System) may account for the alterations in glutamate/GABA neurotransmission in depression.


What Impacts Glial Cell Health


The aforementioned study states that:

Factors such as stress, excess of glucocorticoids (steroid hormones), altered gene expression of neurotrophic factors and glial transporters, and changes in extracellular levels of neurotransmitters released by neurons may modify glial cell number and affect the neurophysiology of depression. Therefore, we will explore the role of these events in the possible alteration of glial number and activity, and the capacity of glia as a promising new target for therapeutic medications.

Stress, hormone imbalances, gene expression (which can be affected by internal and external factors), can modify glial cells enough to affect the neurophysiology of depression.


Resources


Information on the Glial cells and their impact on our mental and physical health and functioning is ever evolving. Here are some resources to dive into to get more familiar with the topic:


Book: The Angel and the Assassin: The Tiny Brain Cell That Changed the Course of Medicine



























 


References:


Öngür, D., Bechtholt, A. J., Carlezon, W. A., Jr, & Cohen, B. M. (2014). Glial abnormalities in mood disorders. Harvard review of psychiatry, 22(6), 334–337. https://doi.org/10.1097/HRP.0000000000000060


Science ABC. (2020, September 18). Glial cells: Definition, types, functions of glial cells | role in psychology. [Video]. Youtube. https://www.youtube.com/watch?v=FaeFaiveb_Q


E, Rebecca (2019). Six types of neuroglia. Sciencing. Retrieved from





Sathyajith, D (2020). What are glial cells? Medical Life Sciences News. Retrieved from


Lee, E. J., Choi, M. J., Lee, G., Gaire, B. P., Choi, J. W., & Kim, H. S. (2017). Regulation of neuroinflammation by matrix metalloproteinase-8 inhibitor derivatives in activated microglia and astrocytes. Oncotarget, 8(45), 78677–78690. https://doi.org/10.18632/oncotarget.20207


Rajkowska, G., & Miguel-Hidalgo, J. J. (2007). Gliogenesis and glial pathology in depression. CNS & neurological disorders drug targets, 6(3), 219–233. https://doi.org/10.2174/187152707780619326

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