Further, two-photon laser scanning microscopy allowed visualization of fluorescent resting microglia in the brain of alive animals, showing that these glial cells research continuously patrol the CNS parenchyma several times a day through stochastic movements of their long and fine branches maintaining tissue integrity (Davalos et al. 2005; Nimmerjahn et al. 2005). Under physiological conditions, there exist mechanisms assuring that microglial cells do not develop patterns of activation with undesirable consequences for CNS integrity (Bessis et al. 2007;
Ransohoff and Perry 2009). Neurons control microglial function by physical contact or by releasing neurotransmitters, peptides Inhibitors,research,lifescience,medical and/or growth Inhibitors,research,lifescience,medical factors including gamma-aminobutyric acid (GABA), glutamate, catecholamines, CD22, CCL21, fraktalkine, which act on receptors present on microglia membrane (Bessis et
al. 2007). It has been shown that in organotypic hippocampal cultures active neurons release neurotrophins, such as neural growth factor (NGF), which control the expression of major histocompatibility Inhibitors,research,lifescience,medical class II (MHC-II) in microglia by acting, at least partially, on the p75 neurotrophin receptor (Neumann et al. 1998). Neuronal secretion of CD22 inhibits microglial release of pro-inflammatory cytokines by acting on CD45 receptor (Mott et al. 2004) and expression of CD200 may be important for controlling tumor necrosis factor-α (TNF-α) released by these glial cells (Broderick et al. 2002; Lyons et al. 2007). Finally, physical interaction between neuronal CD200
and CD200R present on microglia membrane likely represents an alternative way by which neurons Inhibitors,research,lifescience,medical can control microglial function (Broderick et al. 2002; Lyons et al. 2007). Microglia also express a number of neurotransmitter receptors indicating that activity-related release of neurotransmitters by neurons contribute for microglial control in physiological conditions (Bessis et al. 2007). These data clearly illustrate the necessity of controlling both inflammatory and immune microglial functions in physiological conditions in order to maintain the integrity of CNS circuits. Microglia and Adult Inhibitors,research,lifescience,medical Neurogenesis New neurons are generated in the adult brain from neural stem/progenitor Casein kinase 1 cells present in the subventricular zone (SVZ) (Doetsch et al. 1997; Alvarez-Buylla and Garcia-Verdugo 2002) and subgranular zone of hippocampal dentate gyrus (Seri et al. 2001). Microglia seem to play an important physiological role of controlling adult neurogenesis in normal conditions (Aarum et al. 2003; Walton et al. 2006; Ekdahl et al. 2009). In vitro, mouse-derived microglia release soluble factors, which contribute to migration and differentiation of neural progenitors (Aarum et al. 2003; Walton et al. 2006). Microglia instruct neurogenesis in adult SVZ in culture (Walton et al. 2006). In adherent culture systems, there is a normal senescence and decrease in the number of progenitor cells (Walton et al. 2006).