At 5 months, detectable levels of tau phosphorylated at epitope selleck chemical ser199 202 were observed in vehicle Inhibitors,Modulators,Libraries treated rTg4510 mice. LPS significantly increased p tau ser199 202 in the ante rior Inhibitors,Modulators,Libraries cortex and entorhinal cortex in rTg4510 mice compared to the vehicle treated rTg4510 mice. Although the mean % area for staining of phospho tau ser199 202 in the hippocampus following LPS administration showed an elevated trend, it failed to reach statistical significance. Likewise, phospho tau epitope ser396 was observed in vehicle treated mice along axonal processes and in perinuclear Inhibitors,Modulators,Libraries regions, yet LPS induced inflammation further increased phospho tau ser396 immunoreactivity in the cortex, hippo campus, and entorhinal cortex compared to rTg4510 mice treated with vehicle.

Neither phospho tau species was detectable at the immunohistochemical level in nontrans genic mice which received vehicle or LPS administration. To identify the impact of LPS induced inflammation on pre tangle Inhibitors,Modulators,Libraries and mature tau pathology, we measured Gallyas silver staining in rTg4510 mice and nontransgenic littermates. Vehicle treated rTg4510 mice at 5 months of age had small but measurable amounts of Gallyas silver positive neurons. Following LPS administration no signifi cant increases or decreases were observed in the anterior cortex, hippocampus, or entorhinal cortex of rTg4510 mice. This suggests that acute LPS induced microglial activation impacts tau phos phorylation but, at least within the first week, does not affect the pre and mature tangles as determined by Gal lyas stain.

We also evaluated full length tau in the anterior cor tex, hippocampus, and entorhinal cortex by immunohis tochemistry. As observed with the silver stain, tau antibody Inhibitors,Modulators,Libraries failed to recognize endogenous mouse tau in nontransgenic mice, under these staining conditions at the immunohistochemisrty level. However, detectable levels were observed in rTg4510 mice in cortical regions and hippocampus, but were not increased by LPS treatment as was the case for phospho tau markers potentially due to recognition of multiple isoforms. Double labeling of phospho tau and microglia To further identify the relationship between phospho tau expressing cells and microglia, we performed double labeling studies on rTg4510 mice following LPS injec tions. Arginase 1 expression was observed in rod and amoeboid like with some branching cells and failed to co localized with cells stained for phospho tau Ser396.

YM1 positive cells were highly branched and also failed to co localize with cells stained with the AT8, however several YM1 positive microglia were clustered around AT8 positive neurons. Furthermore, CD45 positive cells displayed various till cell morphologies from highly branched to amoeboid rod and macrophage like. In gen eral, CD45 activation increased around tau laden areas such as hippo campus.