Microglial cells are derived from myeloid precursor cells during early development (Perry, Nicoll, & Holmes, 2010). They make up the active immune self-defense mechanism in the central nervous system (CNS) (Neumann, Kotter, & Franklin, 2009). Microglia unlike normal neuroglia are extremely motile, and are found in the brain and the spinal cord (Graeber & Streit, 2010). The high motility of microglial cells support the cells’ over all functions. It enables microglial cells to preform homeostatic activity in the CNS in response to injury and environmental cues (Neumann, Kotter, & Franklin, 2009). Microglia’s quick activation to pathogens and damage is one of their essential properties, however, microglia can act as a double-edged sword. Although their beneficial qualities are ample, they can also become the cause of neuronal death.
There are various functions of microglia in a healthy brain. For instance, microglial cells act as phagocytes, which involve a direct, cell-to-cell contact (Banati et al., 1993). There are two main types of phagocytic events a microglial cell can undergo: The first one recognizes apoptotic cellular materials such as phosphatidylserine (PS), and in turn stimulates an anti-inflammatory response while the second one involves removing pathogens and stimulating pro-inflammatory responses as well (Neumann, Kotter, & Franklin, 2009). Moreover, during the resting state, microglial cells are inactive while the FC receptors express a specific chemokine called CX3CR1. Other aspects such as the neurotrophic factors and the anti-inflammatory cytokines suppress the microglial cells. When microglia is activated by glutamate, proinflammatory cytokines, and changes in the extracellular potassium it secretes mediators that direct the immune response. For instance, microglial cells secrete cytokines, chemokines, and prostaglandins (Hayley, 2014). Cytokines promotes communication between cells while Chemokines facilitate chemotaxis and the interferon that have anti viral effects (Hayley, 2014).
Cytokines produced by microglia can either positively or negatively regulate neurons cytokines such as Interleukin 1, interleukin 2, Interleukin 6, and tumor necrosis factor (TNFalpha). Abundant amounts of IL1 and TNFalpha have negative regulations on the myelin sheath in the CNS or also known as oligodendrocyte cells. They exert cytotoxic effects and inhibit the formation of those cells. This was proven in vitro where microglial cells could lyse the oligodedrocytes. Microglia can also induce the formation of a positively regulated cytokine that protects oligodendrocytic cells such as transforming growth factor beta (TGFp1). Essentially, the effects of TNF-a are antagonized by TGFp1 (Banati et al., 1993). Therefore, it is safe to assume that microglia’s initial function is to regulate and maintain a protected environment.
Microglia is not only protective in nature, scientists have linked it to immunodegenerative diseases such as, Alzheimer, and Multiple Sclerosis, and HIV (Graeber & Streit, 2010). For example, the nerve degeneration in Alzheimer’s disease is associated with the over activation of microglia (Li et al., 2014). It is hypothesized that a positive feedback loop will be initiated once microglial cells are active in Alzheimer’s disease due to A-beta deposition and aging (Li et al., 2014). As a result of the feedback loop, microglial cells will start secreting neurotoxic free radicals, cytokines and glutamate agonists that in return will promote further degeneration and apoptosis. (Perry, Nicoll and Holmes, 2010). Long-term activation of microglial cells also promotes nerve tangles by tau protein hyperphosphorylation (Li et al., 2014). Microglial cells are activated by A-beta thus producing a variety of pro-inflammatory factors that produce neurotoxic effect on the brain. Cell inflammatory mediators include tumor necrosis factor (TNF alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), and…