Multiple sclerosis and its symptoms have been widely researched and talked about, but the underlying mechanisms of the disease itself on the cellular level go largely unnoticed by most people.
Microglia are a specialized type of immune cell that play a crucial role in maintaining brain health and the initiation of defense mechanisms to protect the tissue of the central nervous system. As a result, they can either contribute to neuroinflammation or neurodegeneration. Furthermore, microglia are involved in both the demyelination/ remyelination phases of MS (remyelination refers to the restoration of myelin around denuded axons, but a note to add is that this process becomes less efficient with disease progression and/or age). By providing trophic support, repairing damaged tissue, and clearing debris, microglia create a favorable environment for the regeneration of myelin.
Astrocytes, which are just stable, embedded versions of glial cells, are also influenced by the function of microglia. Activated microglia have the ability to activate astrocytes, leading to the production of factors, such as leukemia inhibitory factor, that promote remyelination. To add, astrocytes also recruit microglia to demyelinating lesions in order to boost the removal of myelin debris (remnants of loss of myelin axonal sheath coverage).
Microglia can also be activated, either directly or indirectly, through cytokine production by cells known as T lymphocytes. In turn, these activated microglia create chemokines and cytokines, which influence the recruitment of immune cells and neuroinflammation (an inflammatory response inside the brain or spinal cord).
Paramagnetic rim lesions (PRLs) have become one of the most important factors for diagnosing MS, especially during it's progressive stages. These types of lesions are characterized by microglia and inflammation, both proinflammatory (M1) and anti-inflammatory (M2), surrounding it. Simply classifying the inflammation into 2 states doesn’t capture all the intricacies of the behavior of microglia, as these lesions also have the ability to switch between M1 and M2. This “switching” behavior is also a characteristic of neurodegenerative diseases. Moreover, research has indicated that signaling pathways such as PI3K-AKT and NF-kB within microglia can drive neuroinflammatory responses in MS, which can help develop new therapeutic interventions.
To conclude, the failure of remyelination presents a significant hurdle in the search for effective MS treatments. The multifaceted role that microglia plays in the pathogenesis of MS is still something that needs to be further studied. While they can contribute to the inflammatory processes in the nervous system, they also have the potential to support myelin regeneration and tissue repair within MS patients, potentially slowing disease progression.
Xue, Zhenxiang, et al. “Microglia in the Context of Multiple Sclerosis.” Frontiers in Neurology, vol. 14, Frontiers Media, June 2023, https://doi.org/10.3389/fneur.2023.1157287.
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