All four white matter regions examined demonstrated a significant increase in CD11c expression with age ( Fig. 4A) and the most caudal area of white matter studied, the inferior selleck compound cerebellar peduncle, exhibited the greatest increase in expression, but CD11c expression was not further influenced by systemic LPS. Although expression of FcγRI was increased in all regions of the

ageing brain, changes in FcγRI expression were more pronounced in white matter areas and the cerebellum than in the hippocampus of 21 month old mice ( Fig. 4B). FcγRI expression after LPS injection was also highest in the three cerebellar regions investigated. Changes in other molecules expressed by microglia during ageing and after systemic LPS injection were investigated in a qualitative manner using immunohistochemistry (data not shown). A small number of Dectin-1 positive Smad inhibitor cells were detected in the white matter tracts of aged animals (3–4 cells per ×20 field of cerebellum), but not in aged grey matter or young white matter. The expression levels of Dectin-1 were not influenced by systemic LPS. DEC-205 positive cells were not observed in either the young or aged brain. We also investigated FcγRII/III and MHCII expression levels and the

majority of positive cells were associated with blood vessels. We could not detect any noticeable changes in the expression of these two molecules on microglia dependent on age or LPS. In summary, age related changes in expression of microglia

associated molecules varied greatly between different brain regions, with the cerebellum and the white matter showing the most pronounced changes, while the effect of systemic LPS on microglia associated molecule expression was limited to FcγRI. To investigate whether the age related, region specific changes in microglial phenotype were associated with compromised CNS function, we performed EGFR antibody behavioural assays dependent on two of the regions analysed for phenotype changes – the hippocampus and the cerebellum. We used burrowing as a measure of hippocampus dependent sickness behaviours (Deacon et al., 2002). A small decline in burrowing activity was seen at baseline with age, which may be attributable to changes in baseline locomotor activity (Supplementary Fig. 1). Between 3 and 5 h after a systemic LPS injection all mice showed a decline in burrowing, with a greater decline in activity in aged mice compared to young mice (Fig. 5A) (LPS group: p < 0.001, n = 14–15). Most 21 month old mice failed to show any burrowing activity (median = 0%), whereas the majority of 4 month old mice retained a degree of burrowing activity (median = 12.1%). There was no age-related effect of saline injection on burrowing (p = 0.233, n = 10–15). At 24 h after injection the LPS-challenged mice had partially recovered their burrowing activity ( Fig.