How was microglia discovered?
1552187#28
Research has discovered dystrophic (defective development) human microglia. "These cells are characterized by abnormalities in their cytoplasmic structure, such as deramified, atrophic, fragmented or unusually tortuous processes, frequently bearing spheroidal or bulbous swellings." The incidence of dystrophic microglia increases with aging. Microglial degeneration and death have been reported in research on Prion disease, Schizophrenia and Alzheimer's disease, indicating that microglial deterioration might be involved in neurodegenerative diseases. A complication of this theory is the fact that it is difficult to distinguish between "activated" and "dystrophic" microglia in the human brain.
Microglia
1552187#30
The ability to view and characterize different neural cells including microglia began in 1880 when Nissl staining was developed by Franz Nissl. Franz Nissl and F. Robertson first described microglial cells during their histology experiments. The cell staining techniques in the 1880s showed that microglia are related to macrophages. The activation of microglia and formation of ramified microglial clusters was first noted by Victor Babeş while studying a rabies case in 1897. Babeş noted the cells were found in a variety of viral brain infections but did not know what the clusters of microglia he saw were. Pío del Río Hortega, a student of Santiago Ramón y Cajal, first called the cells "microglia" around 1920. He went on to characterize microglial response to brain lesions in 1927 and note the "fountains of microglia" present in the corpus callosum and other perinatal white matter areas in 1932. After many years of research Rio-Hortega became generally considered as the "Father of Microglia." For a long period of time little improvement was made in our knowledge of microglia. Then, in 1988, Hickey and Kimura showed that perivascular microglial cells are bone-marrow derived, and express high levels of MHC class II proteins used for antigen presentation. This confirmed Pio Del Rio-Hortega's postulate that microglial cells functioned similarly to macrophages by performing phagocytosis and antigen presentation.
Microglia
4694311#8
Microglial activation has been shown to be a reactive process in which microglia respond to signals given off by injured neurons. Because various characteristics of microgliosis occur in different time frames after the initial triggering insult, microgliosis must depend on mechanisms which fluctuate temporally based on injured neuronal signals. Studies have shown that in cases of reversible neuronal injury, such as axotomy, neuron signals cause microglia to produce trophic factors, which promote neuron survival. In cases of irreversible injury, however, microglia are induced to release neurotoxic factors that promote increased degeneration of the neuron and more rapid phagocytosis by the microglia. Such specificity of the process of microgliosis indicates that it primarily serves a beneficial purpose, selectively conserving some neural tissue while eliminating others, based on the specific initial CNS insult.
Gliosis
1552187#0
Microglia are a collective type of neuroglia (glial cell) located throughout the brain and spinal cord., found to have 9 distinct subtypes with different functions, appearance, and presence. Microglia account for 10–15% of all cells found within the brain. As the resident macrophage cells, they act as the first and main form of active immune defense in the central nervous system (CNS). Microglia (and other neuroglia including astrocytes) are distributed in large non-overlapping regions throughout the CNS. Microglia are key cells in overall brain maintenance—they are constantly scavenging the CNS for plaques, damaged or unnecessary neurons and synapses, and infectious agents. Since these processes must be efficient to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS. This sensitivity is achieved in part by the presence of unique potassium channels that respond to even small changes in extracellular potassium.
Microglia
55439935#37
Glucocorticosteroids (GCS) are anti-inflammatory steroids that inhibit both central and peripheral cytokine synthesis and action. In a study conducted by Kalipada Pahan from the Department of Pediatrics at the Medical University of South Carolina, both lovastatin and sodium phenylacetate were found to inhibit TNF-α, IL-1β, and IL-6 in rat microglia. This shows that the mevalonate pathway plays a role in controlling the expression of cytokines in microglia and may be important in developing drugs to treat neurodegenerative diseases. Naltrexone may provide a solution to the inflammatory mediators produced by microglia. Although naltrexone's main action is to competitively bind to opioid receptors, new research shows that naltrexone, when given in low doses once per day (low-dose naltrexone), can inhibit cytokine synthesis by microglia cells. This mechanism is still being investigated, but there are already studies that indicate that it helps some patients suffering from fibromyalgia syndrome. Naltrexone shows more promise than GCSs because the GCSs inhibit immune system function more generally, increase allergic reactions and, as the name implies, increase blood glucose levels.
Role of microglia in disease
1552187#23
For a long time it was thought that microglial cells differentiate in the bone marrow from hematopoietic stem cells, the progenitors of all blood cells. However, recent studies show that microglia originate in the yolk sac during a remarkably restricted embryonal period and populate the brain mesenchyme. Additionally, they continuously renew themselves and persist throughout life without replenishment from peripheral monocytic precursors.
Monocytes can also differentiate into myeloid dendritic cells and macrophages in the peripheral systems. Like macrophages in the rest of the body, microglia use phagocytic and cytotoxic mechanisms to destroy foreign materials. Microglia and macrophages both contribute to the immune response by acting as antigen presenting cells, as well as promoting inflammation and homeostatic mechanisms within the body by secreting cytokines and other signaling molecules.
Microglia
47972575#1
In 2012, Stevens’s team published evidence that microglia 'eat' synapses, especially those that are weak and unused. The findings pinned down a new role for microglia in wiring the brain, indicating that adult neural circuitry is determined not only by nerve cells but also by the brain’s immune cells; this helped to explain how the brain, which starts out with a surplus of neurons, trims some of the excess away. Neuron named the paper its most influential publication of 2012.
Beth Stevens
14470857#13
Radiation therapy usually results in chronic inflammation, and in the brain this inflammatory response comes in the form of activated microglia cells. Once activated, these microglia cells start to release stress hormones and various pro-inflammatory cytokines. Some of what is released by the activated microglia cells, like the glucocorticoid stress hormone, may result in a decrease in neurogenesis. To investigate this concept, an animal study was performed by Monje et al. in order to determine the specific cytokines or stress hormones that were released by activated microglial cells that decrease neurogenesis in an irradiated hippocampus. In this study, microglia cells were exposed to bacterial lipopolysaccharide to elicit an inflammatory response, thus activating the microglia cells. These activated microglia were then co-cultured with normal hippocampal neural stem cells. Also, as a control, non-activated microglia cells were co-cultured with normal hippocampal neural stem cells. In comparing the two co-cultures, it was determined that neurogenesis in the activated microglia cell culture was 50% less than in the control. A second study was also performed to ensure that the decrease in neurogenesis was the result of released cytokines and not cell-to-cell contact of microglia and stem cells. In this study, neural stem cells were cultured on preconditioned media from activated microglia cells and a comparison was made with a neural stem cells cultured on plain media. The results of this study indicated that neurogenesis also showed a similar decrease in the preconditioned media culture versus the control.
Radiation-induced cognitive decline
1680989#3
Microglia are located throughout the brain and spinal cord. They are the first line of immune defense in the CNS. Microglia are of utmost importance in brain maintenance. They constantly search around the CNS for any type of plaques, damaged neurons, and infections. Microglia are extremely sensitive forms of effector cells, because they must be alert enough to address possible life-threatening damage. This sensitivity is caused by unique forms of potassium channels. Microglia must always be capable of recognizing any foreign bodies, engulf them, and activate T-cells. Microglia can be found under a variety of different shapes and sizes, based on the location where they are found. The vast amount of shapes are required for the microglia to carry out their primary function. Microglia are distinguishable from macrophages because of their ability to transform, which allows them to protect the CNS under relatively short amounts of time. Microglia take on a unique phenotype when they detect local chemical signals. Microglia have a variety of different functions required to maintain homeostasis in the host body.
Effector cell
55439935#12
Many activated microglia are found to be associated with amyloid deposits in the brains of Alzheimer's patients. Microglia interact with β-amyloid plaques through cell surface receptors that are linked to tyrosine kinase based signaling cascades that induce inflammation. When microglia interact with the deposited fibrillar forms of β-amyloid it leads to the conversion of the microglia into an activated cell and results in the synthesis and secretion of cytokines and other proteins that are neurotoxic.
Role of microglia in disease