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Background: Recent studies suggest an important role for neurotransmitters as modulators of inflammation. Neuroinflammatory mediators such as cytokines and molecules of the arachidonic acid pathway are generated and released by microglia. The monoamine norepinephrine reduces the production of cytokines by activated microglia in vitro. However, little is known about the effects of norepinephrine on prostanoid synthesis. In the present study, we investigate the role of norepinephrine on cyclooxygenase- (COX-)2 expression/synthesis and prostaglandin (PG)E2 production in rat primary microglia.Results: Interestingly, norepinephrine increased COX-2 mRNA, but not protein expression. Norepinephrine strongly enhanced COX-2 expression and PGE2 production induced by lipopolysaccharide (LPS). This effect is likely to be mediated by beta-adrenoreceptors, since beta-, but not alpha-adrenoreceptor agonists produced similar results. Furthermore, beta-adrenoreceptor antagonists blocked the enhancement of COX-2 levels induced by norepinephrine and beta-adrenoreceptor agonists.Conclusions: Considering that PGE2 displays different roles in neuroinflammatory and neurodegenerative disorders, norepinephrine may play an important function in the modulation of these processes in pathophysiological conditions. [ABSTRACT FROM AUTHOR]

Microglial activation plays an integral role in the development and course of neurodegeneration. Although neuropeptides such as bradykinin (BK), somatostatin (SST), and endothelin (ET) are known to be important mediators of inflammation in the periphery, evidence of a similar function in brain is scarce. Using immunocytochemistry, we demonstrate the expression of receptors for BK (B1, B2 subtypes), ET (ETA, ETB subtypes) and SST (SST 2, 3, 4 subtypes) in primary microglia and microglial cell lines. Exposure of BV2 and N9, as well as primary microglial cells to BK or SST increased Aβ uptake in a concentration-dependent manner, whereas endothelin decreased Aβ uptake. This was caused by increased phagocytosis of Aβ since the rate of intracellular Aβ degradation remained unaffected. All neuropeptides increased chemotactic activity of microglia. In addition, BK reduced Aβ-induced expression of proinflammatory genes including iNOS and COX-2. ET decreased the Aβ-induced expression of monocyte chemoattractant protein 1 and interleukin-6. These results suggest that neuropeptides play an important role in chemotaxis and Aβ clearance and modulate the brain's response to neuroinflammatory processes. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptors (PPAR) are members of a superfamily of nuclear hormone receptors. Activation of PPAR isoforms elicits both antineoplastic and anti-inflammatory effects in several types of mammalian cells. PPARs are ligand-activated transcription factors and have a subfamily of three different isoforms: PPAR alpha, PPAR gamma, and PPAR beta/delta. All isoforms heterodimerise with the 9-cis-retinoic acid receptor RXR, and play an important part in the regulation of several metabolic pathways, including lipid biosynthesis and glucose metabolism. Endogenous ligands of PPAR gamma include long-chain polyunsaturated fatty acids, eicosanoid derivates, and oxidised lipids. Newly developed synthetic ligands include thiazolidinediones-a group of potent PPAR gamma agonists and antidiabetic agents. Here, we review PPAR gamma-induced antineoplastic signalling pathways, and summarise the antineoplastic effects of PPAR gamma agonists in different cancer cell lines, animal models, and clinical trials. [ABSTRACT FROM AUTHOR]

Inflammatory and immunological processes interfering with brain development are discussed as one cause of schizophrenia. Various signs of overactivation of the immune system were often found in this disease. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, PolyI:C incubation of pregnant dams was used as animal model of schizophrenia, and the number and shape of microglia were assessed in the offspring in the early phase of this disease, using fluorescence immunostaining (Iba1). Descendants of mice exposed to PolyI:C at embryonic day 9 showed higher number of microglial cells in the hippocampus and striatum, but not in the frontal cortex at postnatal day 30, which is similarly to adolescence in man, as compared to those exposed to saline. Furthermore, offspring microglia from PolyI:C treated mothers were morphologically characterized by a reduced arborization indicative for a status of higher activation compared to the offspring microglia from vehicle treated mice. This study supports the hypothesis that maternal infection during embryogenesis contributes to microglial activation in the offspring, which may therefore represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options in this regard. [ABSTRACT FROM AUTHOR]