Fig. 3.

ER-α mediates the inhibitory activity of E₂ on microglia activation. MMP-9 expression in the CA1 region of wild-type (A–C), ERβ-null (D–F), and ERα-null (G–I) mice injected icv with saline (A, D, and G), LPS (B, E, and H), or E₂ before LPS (C, F, and I). (J and K) Quantification of estrogen activity on the number of MMP-9-positive (J) and C3R-positive (K) cells per mm² in the CA1 region of mice with different ER genetic background. Saline, LPS, and E₂ + LPS treatments are represented as open, filled, and dashed bars, respectively. Bars are from a single representative experiment, repeated at least three times. Values represent the mean ± SD of cells counted in different adjacent sections. *, P < 0.01 vs. control; **, P < 0.01 vs. LPS. (L–O) Disruption of ERα results in brain microglia activation. Microglial cells were visualized by immunohistochemistry of C3R on brain coronal sections of ERα-null mice at 4 mo (L and M) or 2 mo (N and O) of age. (L) Strong C3R staining shows a reactive phenotype in the parietal cortex (PtCx), DG, temporal cortex (TeCx), rhinal cortex (RhCx), and amygdaloid nuclei (AN; see arrows). (M and O) Enlargements showing the reactive phenotype of microglia only in a 4-mo-old ERα-null mouse. Sections were counterstained with methyl green. (Filled bars = 35 μm, dashed bars = 1.2 mm, and open bars = 7 μm.)