Microglia phenotypes

The Missing Link—Adaptive Immunity Controls Microglia Phenotype Needed for Survival, Regrowth, and Renewal... 

In the long-term survival monkey group, microglia again represented the largest proportion of BrdU+ cells (Fig. 23A Table 5). In addition, a few 2/,3/-cyclic nucleotide 3 -phosphodiesterase (CNP)+ oligodendrocytes incorporated BrdU in the postischemic monkeys (Fig. 23B Table 5). In the control CA, we identified just 1-2 BrdU+/CNP+ cells representing about 0.5% of the BrdU+ cells. Thus, in the control monkeys most of the BrdU+ cells were of an unidentified phenotype. 

Investigating the phenotype of BrdU+ in PHR we did not observe differences between control and postischemic brains. A proportion of BrdU+ cells (up to 15%) expressed the phenotype of either microglia or astroglia (Fig. 30A), and some vascular cells incorporated BrdU as well. BrdU+ oligodendrocytes or cells with a neuronal phenotype were not observed (Fig. 30B). Thus, over 75% of the BrdU+ cells in the PHR were of an unknown phenotype. 

In contrast to DG, no signs of neuronal production were detected in postis-chemic CA1, where despite the marked cell loss followed by a striking increase of proliferating cells, the latter were invariably of a glial phenotype. Most BrdU+ cells in monkey CA1 were microglia, as with the rodent brain (Liu et al. 2001b) ... 

Since activated microglia are implicated in exacerbating brain diseases, the biochemical markers and pathways that are stimulated by microglia in injury have been extensively studied. Several recent evidences clearly demonstrate that microglial phenotype after injury could be either destructive or protective (Butovsky et al., 2001 Nelson et al., 2002 Butovsky et al., 2005). In response to various stimuli, microglial cells will produce different sets of dominant compounds that differentially affect the fate of neural tissue. The partial list of common compounds can be found in Table 9.3. 

Recent results showed that exposure of microglia to Ap, reminiscent of exposure to EPS, resulted in a cytotoxic microglial phenotype. Cytotoxicity was associated with upreguladon of TNF-a. The cytotoxicity induced by EPS or by Ap could be partly overcome by pred eatment of the microglia with lE-4 in-vitro (Butovsky et al., 2005). Other stucUes have shown that the indue don of TNF-a expression in microglial cells by Ap is dependent on the fibrillary state of the pepdde thus, for... 

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