, 1993), and that the microglia may appear in “clumps” of immunoreactive membranes in white matter (Perry et al., 1993 and Stichel and Luebbert, 2007). Our study shows that these aggregates are not directly associated with blood vessels and are not clusters of proliferating cells. Macrophages and microglia are known to form multinucleate

giant cells through fusion under a variety of inflammatory conditions (Fendrick et al., 2007, Gasser and Most, 1999 and Suzumura et al., 1999). Whether these cells are aggregates of individual microglia or a single syncytium is not clear from our study, but the appearance of multinucleate giant cells during ageing would represent a significant alteration in microglial phenotype and function. We observed a significant increase in CD11c expression levels, predominantly in the white matter of the cerebellum. CD11c selleck screening library is a protein found at high levels on dendritic cells, but is also found on macrophages and microglia under neuroinflammatory conditions (Reichmann et al., 2002 and Remington Natural Product Library screening et al., 2007). Increases in CD11c immunoreactivity with age have been reported previously with robust CD11c expression

in the aged white matter and occasional CD11c expression throughout the grey matter (Kaunzner et al., 2010 and Stichel and Luebbert, 2007). These studies describe CD11c positive cells as dendritic cells, as they express DEC-205, MIDC8, MHCII and the co-stimulatory molecules CD80 and CD86. Using immunohistochemistry we did not detect Dimethyl sulfoxide DEC-205 or MHCII expression in the aged brain. This discrepancy may be

explained by the superior sensitivity of alternative methods of detection, such as flow cytometry, or by the strain of mice used (Henry et al., 2009). The functional consequence and mechanism underlying increased expression of CD11c in the aged brain is unknown, but increased turnover of myelin with age may be a contributing factor (Ando et al., 2003). It has been shown that engagement of low density lipoprotein receptor 1 (LRP-1) on macrophages results in increased expression of CD11c (Cho et al., 2007 and Gower et al., 2011). Ligands for LRP-1 include low density lipoprotein (Kuchenhoff et al., 1997) and the myelin component MBP-1 (Gaultier et al., 2009). Whether the CD11c + cells in our study are microglia that have taken up myelin components/breakdown products, or infiltrating dendritic cells or macrophages remains to be determined. It is well recognised that the microglia are exquisitely sensitive to neurodegeneration. However, in rodents and primates the extent to which neurodegeneration occurs in the ageing CNS varies considerably from region to region. The substantia nigra (Ma et al., 1999 and Mouton et al., 2010) and cerebellum (Sturrock, 1989 and Woodruff-Pak et al., 2010) exhibit significantly greater age-related neuronal loss than the hippocampus (Calhoun et al.