The Multifaceted Profile of Activated Microglia

Abstract

Although relatively neglected previously, research efforts in the past decade or so have identified a pivotal role for glial cells in regulating neuronal function. Particular emphasis has been placed on increasing our understanding of the function of microglia because a change from the ramified "resting" state of these cells has been associated with the pathogenesis of several neurodegenerative diseases, notably Alzheimer's disease. However, it is not clear whether activation of microglia and the associated inflammatory changes play a part in triggering disease processes or whether cell activation is a response to the early changes associated with the disease. In either case, the possibility exists that modulation of microglial activation may be beneficial in some circumstances, underlying the need to pursue research in this area. The original morphological categorization of microglia by Del Rio Hortega into ameboid, ramified, and intermediate forms, must now be elaborated to encompass a functional description. The evidence which has been generated recently suggests that microglia are probably never in a "resting" state and that several intermediate transitional states, based on function and morphology, probably exist. A more complete understanding of these states and the triggers which lead to a change from one to another state, and the factors which modulate the molecular switch that determines the persistence of the "activated" state remain to be identified.

Apelin activates the expression of inflammatory cytokines in microglial BV2 cells via PI-3K/Akt and MEK/Erk pathways

“…They have potent chemoattractant capability and promote monocyte recruitment into an inflammatory or pathological site. Once they were activated near the site of pathology, the recruited cells can produce more inflammatory mediators, thus inducing inflammation response [10,36]. Similarly, MCP-1 and MIP-1α in vitreous fluid from PDR patients were significantly higher than that of from control groups [37].…”

“…Studies have demonstrated that microglial cells are involved in phagocytosis, removal of apoptotic neuronal remnants and involved in remodeling [10]. Furthermore, when they are over-activated, microglial cells release soluble cytotoxins, such as tumor necrosis factor-alpha (TNF-α), interleukin1β (IL-1β), and IL-6 that can contribute to neuronal and vascular cell death and ultimately the progression of diabetic retinopathy (DR) [11].…”

Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A4 analog: Protective mechanisms and long‐term effects on neurological recovery

“…These cells can fall into a spectrum defined by a classical, pro‐inflammatory M1 phenotype, and an alternative, anti‐inflammatory M2 phenotype. M1 cells drive the inflammatory response via pro‐inflammatory cytokine and MMP‐3/‐9 release and have detrimental effects on neurons (Lynch, 2009). The receptor CD40 is a marker of M1 cells, as cytokine binding (such as TNF‐α) and its ligand CD40L can lead to the activation of inflammatory pathways and result in the formation of ROS, pro‐inflammatory cytokines and chemokines, and the upregulation of adhesion molecules on endothelial cells (Benveniste, Nguyen, & Wesemann, 2004; Tan et al., 1999).…”

Impact of Prenatal Immune System Disturbances on Brain Development

“…Whether these properties also relate to the observed differences in the basal activation state of microglia in white versus grey matter (Carson et al, 2007), remains to be determined. However, it is conceivable that these functional differences are linked to the expression profile of cell surface markers, through which microglia are not only able to control distinct population of neurons but also modulate a variety of cellular and immune functions (for recent review, Lynch, 2009). For instance, microglia can promote the infiltration of circulating cells into the CNS (upregulation of CD11b), can be non-phagocytic and produce proinflammatory molecules (CD40), or be phagocytic and motile (MHCII), as shown for the highly effective clearance of In the adult brain, microglia are responsible for all apoptotic debris, including the majority of new born neurons (Sierra et al, 2010).…”