Activation of microglia

Evidence for a neuroimmunological involvement in Alzheimer s disease is accumulating. Activation of the complement cascade by beta amyloid (Rogers et al., 1992), the recruitment, proliferation and activation of microglia in intimate juxtaposition to the senile plaques (Davis et al., 1992), and the increased synthesis of microglia-derived pro-inflammatory cytokine interleukin-1 (Griffin et al., 1989) is indicative of a chronic inflam-... 

DeSimone, R., Ajmone-Cat, M. A. and Minghetti, L. Atypical anti-inflammatory activation of microglia induced by apoptotic neurons. Mol. Neurobiol. 29 197-212, 2004. 

What are the possible adverse consequences of accumulation of the A(3 protein It may cause inflammation by activation of microglia,1157 which may cause damage by release of NO.1206 A(3 may induce death of neurons by apoptosis.1201 1207-1209 A defect in protesomal degradation may be a factor.1208 Both Ap and the prion protein may promote oxidative damage. The brain derives most of its energy from oxidative metabolism, a major source of damaging radicals. Mitochondria are found in dendrites as well as cell bodies.1210 Methionine residues in glycine-rich parts of the AP and prion proteins are suspected as centers of free radical formation.1202 1211... 

Wilms H., Rosenstiel P., Sievers J., Deuschl G., Zecca L., and Lucius R. (2003). Activation of microglia by human neuromelanin is NF-/cB dependent and involves p38 mitogen-activated protein kinase implications for Parkinson s disease. FASEB J. 17 500-502. 

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. 

Shaked I, Porat Z, Gersner R, BGpnis J, Schwartz M (2004) Early activation of microglia as antigen-presenting cells correlates with T cell-mediated protection and repair of the injured central nervous system. J Neuroimmunol 146 84—93. 

Wang Q, Rowan MJ, Anwyl R (2004a) Beta-amyloid-media ted inhibition of NMDA receptor-dependent long-teim potentiation induction involves activation of microglia and stimulation of inducible nitric oxide synthase and superoxide. J Neurosci 24 6049-6056. 

Bayer TA, Buslei R, Havas L, Falkai P (1999) Evidence for activation of microglia in patients witli psycliiatiic illnesses. Neurosci Lett 271 126-128. 

Butovsky O, Talpalar AE, Ben-Yaakov K, Schwartz M (2005) Activation of microglia by aggregated beta-amyloid or hpopolysaccharide impairs MHC-II expression and renders them cytotoxic whereas IFN-gamma and IL-4 render them protective. Mol Cell Neurosci 29 381-393. 

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