Microglia in Neurodegenerative Events—An Initiator or a Significant Other?

Abstract

A change in microglia structure, signaling, or function is commonly associated with neurodegeneration. This is evident in the patient population, animal models, and targeted in vitro assays. While there is a clear association, it is not evident that microglia serve as an initiator of neurodegeneration. Rather, the dynamics imply a close interaction between the various cell types and structures in the brain that orchestrate the injury and repair responses. Communication between microglia and neurons contributes to the physiological phenotype of microglia maintaining cells in a surveillance state and allows the cells to respond to events occurring in their environment. Interactions between microglia and astrocytes is not as well characterized, nor are interactions with other members of the neurovascular unit; however, given the influence of systemic factors on neuroinflammation and disease progression, such interactions likely represent significant contributes to any neurodegenerative process. In addition, they offer multiple target sites/processes by which environmental exposures could contribute to neurodegenerative disease. Thus, microglia at least play a role as a significant other with an equal partnership; however, claiming a role as an initiator of neurodegeneration remains somewhat controversial.

The effects of bioactive components from the rhizome of gastrodia elata blume (Tianma) on the characteristics of Parkinson’s disease

“…Since glial cells have bidirectional communication with neurons, loss of dopaminergic neurons is accompanied by a significant increase in the number of reactive glial cells in the SN in PD patients ( Mani et al, 2021 ). Microglia are the primary glial cells for mediating the innate immune response against invading pathogens and scavenging damaged neurons, synapses, as well as abnormally aggregated proteins in the central nervous system through phagocytosis ( Harry, 2021 ; Zhong et al, 2022 ). However, alterative immune response of microglia can be activated by secreted molecules from degenerative neurons, which leads to the secretion of pro-inflammatory cytokines such as Interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) to the brain microenvironment ( Figure 3C ).…”

The Role of Glucocorticoids in Inflammatory Diseases

“…Paradoxically, pro-inflammatory activities of GCs in the CNS have been described, too, and hypothesized to be dependent on FKBP51, a protein that sequesters the GR in the cytosol [ 61 ]. Since communication between neurons and microglia is essential for maintaining neuronal homeostasis [ 62 ], a reduced microglial activity by GCs could render neurons more vulnerable to damage [ 63 ]. However, it was also found that hippocampal microglia were primed by GCs for enhancement of LPS-induced pro-inflammatory factors [ 64 , 65 ].…”

Age-Associated Glia Remodeling and Mitochondrial Dysfunction in Neurodegeneration: Antioxidant Supplementation as a Possible Intervention

“…In the setting of reduced glial activity, several stressors and/or injury signals can trigger a coordinated action of microglia and astrocytes that may amplify neuroinflammation and contribute to the release of neurotoxic factors [26]. In this regard, an overall decline in processes involved in preserving cell's quality may play a major role.…”