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. 2017 Dec 8;141(1):132–147. doi: 10.1093/brain/awx315

Figure 2.

Figure 2

ERβ expression in CD11c+ cells is necessary for neuroprotection in EAE. (A) Breeding scheme for creating wild-type (WT) and CKO mice of ERβ in CD11c+ cells. Briefly, CD11c-Cre-GFP+ mice were crossed with mice carrying an ERβ (Esr2) gene flanked by LoxP sites (ERβfl/fl). Homozygous ERβfl/fl mice without (WT) or with (CKO) Cre were generated. Each genotype was separated into two groups and received either vehicle or ERβ-ligand, DPN, treatment (tx). EAE was induced and animals were monitored daily and scored using the standard EAE 0–5 scale. ERβ-ligand treated wild-type EAE mice (WT-ERβ, blue solid) had significantly better clinical scores compared to vehicle treated wild-type EAE mice (WT-V, blue clear), ***P (WT-V versus WT-ERβ) = 0.0002, after Day 20 of EAE. In contrast, ERβ-ligand mediated protection did not occur in ERβ-ligand treated CKO EAE mice (CKO-ERβ, black solid) when compared to vehicle treated CKO EAE mice (CKO-V, black clear), P (CKO-V versus CKO-ERβ) > 0.9999. Detailed EAE statistics are in Supplementary Tables 1 and 2. (B) Representative images and quantitative analyses of NF200+, SMI32+, and βAPP+ axons in dorsal white matter of the spinal cord. Images were taken at 40× magnification. Scale bar = 20 μm. (C) Representative images and quantitative analyses of MBP+ and CNPase+ mean intensity in dorsal white matter of the spinal cord. Scale bar = 100 μm. (D) Representative electron microscopy images of ultraresolution of axons and myelin thickness in the dorsal white matter of spinal cord. Myelin thickness in the wild-type and CKO EAE mice treated with vehicle and ERβ-ligand was measured using the g-ratio (axon diameter) / (axon + outer myelin diameter) and shown in comparison with normal. Quantitative analysis showed that ERβ-ligand treated wild-type EAE mice had a decrease in g-ratio due to increased outer myelin diameter, while CD11c ERβ CKO mice with EAE did not. Scale bar = 1 μm. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. Data are representative of three repeated experiments.