Microglial Activation and Chronic Neurodegeneration

Abstract

Summary: Microglia, the resident innate immune cells in the brain, have long been implicated in the pathology of neurodegenerative diseases. Accumulating evidence points to activated microglia as a chronic source of multiple neurotoxic factors, including tumor necrosis factor-␣, nitric oxide, interleukin-1␤, and reactive oxygen species (ROS), driving progressive neuron damage. Microglia can become chronically activated by either a single stimulus (e.g., lipopolysaccharide or neuron damage) or multiple stimuli exposures to result in cumulative neuronal loss with time. Although the mechanisms driving these phenomena are just beginning to be understood, reactive microgliosis (the microglial response to neuron damage) and ROS have been implicated as key mechanisms of chronic and neurotoxic microglial activation, particularly in the case of Parkinson's disease. We review the mechanisms of neurotoxicity associated with chronic microglial activation and discuss the role of neuronal death and microglial ROS driving the chronic and toxic microglial phenotype.

An efficient method to limit microglia-dependent effects in astroglial cultures

“…Microglia, the most reactive cells against pro-inflammatory stimuli, detect and respond rapidly to pro-inflammatory triggers (Lull and Block, 2010;Kim and Joh, 2006). Based on previous papers, astrocyte-mediated effects are completely masked when cultures contain a large population of microglia.…”

“…In their activated state, they have beneficial functions essential for neuron survival (Ekdahl et al, 2009). On the other hand, microglial overactivation can give rise to progressive neurotoxic consequences (Lull and Block, 2010;Block et al, 2007). Microglial activation can also promote astrocyte activation, which in turn can further activate microglia, thus possibly leading to a vicious cycle of overactivation that may contribute to a chronic inflammatory state, with continuously increasing production of pro-inflammatory mediators (Liu et al, 2011;Vallejo et al, 2010;Saijo et al, 2009;Henze et al, 2005;Zaheer et al, 2002).…”

Influence of CSN1S2 protein from Caprine milk Etawah Breed (EB) on histology of microglial cells in rat (Rattus norvegicus) Type-2 diabetes mellitus (T2DM)

“…Proliferation is one of the regeneration methods of tissue when injury stimulation exists and activation of immunocompetent cells occurs. 14 The cerebrum is the main control organ for many mechanisms in the body. In histological observation, in both control and T2DM rats, there are capillaries, microglial cells, astrocyte cells, neutrophils, and neurons.…”

Kinins and microglial responses in bipolar disorder: a neuroinflammation hypothesis

“…Activated microglia can be either neuroprotective (M2 subtype) or neurotoxic (M1 subtype), depending on microenvironmental conditions (Kraft and Harry, 2011;Ekdahl, 2012;Weitz and Town, 2012). In many neurological diseases, including BD, microglial cells are found in a hyperactivated state causing neuroinflammation through release of TNF-α, IL-1β, IL-6 and NO (Weitz and Town, 2012), furthering neuronal damage and loss (Lull and Block, 2010). However, the exact underlying mechanism of microglia hyperactivation in BD is still unknown.…”