Microglia, activation

De Jong EK, Dijkstra IM, Hensens M, et al. Vesicle-mediated transport and release of CCL21 in endangered neurons a possible explanation for microglia activation remote from a primary lesion. J Neurosci 2005 25 7548-7557. 

Iron has been implicated in many neurodegenerative diseases, particularly microglia activation and mitochondrial dysfunction. 

Figure 18.16 Hypothetical model for the metallobiology of AP in Alzheimer s disease. (From Bush, 2003. Copyright 2003, with permission from Elsevier.) The proposed sequence of events (1) concentration of iron and copper increase in the cortex with aging. There is an overproduction of APP and AP in an attempt to suppress cellular metal-ion levels. (2) Hyper-metallation of AP occurs which may facilitate H202 production. (3) Hyper-metallated AP reacts with H202 to generate oxidized and cross-linked forms, which are liberated from the membrane. (4) Soluble AP is released from the membrane and is precipitated by zinc which is released from the synaptic vesicles. Oxidized AP is the major component of the plaque deposits. (5) Oxidized AP initiates microglia activation. (6) H202 crosses cellular membranes to react with Cu and Fe, and generate hydroxyl radicals which oxidize a variety of proteins and lipids.

Gomes-Leal W., Corkill D. J., Freire M. A., Picanjo-Diniz C. W., and Perry V. H. (2004). Astrocytosis, microglia activation, oligodendrocyte degeneration, and pyknosis following acute spinal cord injury. Exp. Neurol. 190 456 167. 

Hsiao G., Fong T. H., Tzu N. H., Fin K. H., Chou D. S., and Sheu J. R. (2004). A potent antioxidant, lycopene, affords neuroprotection against microglia activation and focal cerebral ischemia in rats. In Vivo 18 351-356. 

Adrenoreceptors have been identified in microglia and the role of NE has been investigated in microglia activation. In vitro, microglia can be activated by different stimuli, like LPS, amyloid-P, IL-ip, TNFa and IFNy. However, the most used activator of microglia in in vitro studies is LPS. Stimulation of microglia with LPS leads to the increase in the production of different inflammatory mediators, like nitric oxide (NO), prostaglandins (PG), cytokines and others. 

Rebe S, Solomon B. Deglycosylation of anti-beta amyloid antibodies inhibits microglia activation in BV-2 cellular model. Am J Alzheimers Dis Other Demen 2005 20(5) 303-13. 

As the CNS representatives of the monocytic cell lineage, microglia undergo an inflammatory type of activation in response to brain injury and stress. Among the products of microglia activated by inflammatory signals is nitric oxide, which is produced by the exquisitely NF-KB-sensitive, inducible nitric oxide synthase. This enzyme can be elevated in an NF-xB-dependent manner in astrocytes (Akama et al.,... 

Butovsky O, Ziv Y, Schwartz A, Landa G, Talpalar AE, Pluchino S, Martino G, Schwartz M (2006a) Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol Cell Neurosci 31 149—160. 

Previously, the brain was thought to be an immune-privileged organ. Now it is clear that the brain does respond to peripheral inflammatory stimuli through both neural and humoral afferent signals. The concept that the microglia act as the brain s immune system has also become widely accepted. The inflammatory responses in the brain have different features from those of nonneuronal tissues. Microglia activation and elevated levels of cytokines and... 

The effect of chronic stress on the peripheral immune system and its relevance for major depression has extensively been discussed (O Brien et al., 2004). Recent in vivo evidence now suggests that stress-induced elevation of glucocorticoids also enhances immune function within the CNS through microglia activation and proliferation. Animal studies show that stress induces an enhanced expression of proinflammatory factors like IL-1(3 (Pugh et al., 1999 Nguyen et al., 1998), macro-... 

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