Microglia proliferation, rod-like microglia, astrocyte activation and myelin degeneration.
(A) Representative images of Iba1-immunoreactivity in the CA1 region of the hippocampus, at 10- and 18–20-month-old rats, demonstrating both microglia proliferation and morphological changes occur by the late time point. Quantification of microglia numbers per field of view (FOV) in hippocampal regions subiculum (Sub), CA1 and hilus at the (B) 10 and (C) 18–20-month time points highlight the increase in microglia numbers (n = 7–8/group). (D) Microglia phenotypes at the two time-points are summarised. (E) Rod-like microglia form trains that run parallel to neuronal projections throughout hippocampal regions and the somatosensory cortex. (F) Representative images of hippocampal astrocyte GFAP-immunoreactivity demonstrating a more reactive phenotype in R962-hTau rats at the 18–20-month time point. This is supported by the quantification of the percent area covered, and fluorescence intensity in the CA1 and molecular dentate gyrus (DG) layers at the (G) 10- and (H) 18-month time points (n = 7–8/group). (I) Micrographs demonstrating apparent myelin loss in the R962-hTau 18-month-old rat compared to control rats (n = 6/group). Scale bar, A 100 μm; E,F 50 μm; I 1000 μm. Values are expressed as means ± SEM. Bonferroni-Holm corrected Welch's t-tests were used. ***p < .001.