Fig. 4

Histological analysis of neuroinflammatory readouts in the hippocampus 2 months after 3 × versus 5 × tamoxifen induction. a Representative coronal sections demonstrating persistent neuroinflammatory changes in DTA mice dependent on the tamoxifen dose. In the hippocampus of DTA mice, changes include increased microglia (Iba1⁺ cells, white) and GFAP (red) density as well as apparent changes in morphology. High-resolution images of CA1, CA3 and dentate gyrus (DG) regions were acquired as 10 µm Z-stacks and are displayed as maximum-intensity projections. b To assess atrophy in hippocampal regions, 4–6 hippocampi per mouse (within Bregma -1.34 mm and -1.94 mm) were manually segmented and areas of respective regions normalized to the mean of control mice. DTA mice after both tamoxifen doses showed strong atrophy in whole hippocampus (HC) and particularly its CA regions, whereas the DG was only weakly affected. c Evaluation of astrogliosis in DTA compared to control mice. Prominent astrogliosis was observed in HC and CA regions of DTA mice in both tamoxifen dose groups, while the DG remained relatively unaffected. The GFAP⁺ area fraction was determined densitometrically upon uniform thresholding, and fold changes were calculated based on the mean of control mice. d Quantification of Iba1⁺ cells (microglia). DTA compared to control mice showed increased microglia numbers in all hippocampal regions. Data from 7–8 mice/group displayed as mean ± SD; 2-tailed unpaired Welch’s corrected t-tests or Mann–Whitney U-tests