Article Figures & Data
Figures
- Figure 1.
Transfer of lymphocytes from stressed mice confers behavioral resilience in two strains of Rag2−/− mice. The experimental time line is shown in A. Following adoptive transfer (AT) of cells from SD or HC donors, SD→Rag mice on a C57BL/6 background (n = 12–16 per group; B) showed increased time in light and elevated transitions in the L/D box, increased center time in the OFT, increased mobility in the TST, and enhanced preference for SI. Behavioral profiles between C57BL/6 WT and naive Rag2−/− mice on the same background were comparable. SD→Rag mice on 129 background (n = 6–8 per group; C) showed comparable anxiolytic changes in the L/D test and significantly enhanced expressions of socially affiliative behaviors measured in the USM and SI tests. Post hoc significances marked. *p < 0.5; **p < 0.01; ***p < 0.001. Heat maps show digitized behavior in the SI task, and binarized maps show marking behavior to female urine in the USM test.
- Figure 2.
Transfer of lymphocytes from stressed mice increases hippocampal DG cell proliferation in the C57BL/6 (A) and 129 (B) strains of Rag2−/− mice and increases SI-induced corticosterone (CORT) levels in C57BL/6 mice (n = 10–16 per group; C). The increases in SD→Rag mice were relative to naive and HC→Rag mice with significances indicated. Representative photomicrographs of the BrdU-labeled cells in the DG of the two strains are shown. Scale bar, 100 μm.
- Figure 3.
Levels of several plasma cytokines are increased by SD stress relative to HC control mice, but the relationship is reversed in Rag2−/− mice receiving cells from those animals. In HC→Rag mice elevations relative to naive control were seen for some cytokines. In the SD→Rag mice, reductions in levels were seen for pro-inflammatory cytokines and increases in levels of the anti-inflammatory cytokine IL-4 were seen relative to the other groups, with significances shown (n = 4–6 per group).
- Figure 4.
The relative abundance of lymphocyte subpopulations was not affected by SD stress compared with HC control conditions (n = 6 per group). Representative bivariate dot plots show lymphocytes from donor mice and host Rag2−/− mice (examples are from lymph nodes taken from mice in defeat conditions) stained and gated for B cells, T cells, and T cell subsets. The table shows that ratios of CD19+, CD3+, CD4+, and CD8+ cells as well as the proportion of CD25+ regulatory CD4+ T cells were not affected.
- Figure 5.
Cell-proliferation rates of adoptively transferred (AT) cells in the Rag2−/− mice were not affected by SD stress in the donor mice. The CFSE intensity histograms show that most cells underwent >8 divisions in the period after the two transfers (8 and 14 d prior). Two representative histograms are shown for lymph node cells from HC→Rag and SD→Rag mice. Successive cell divisions to the left of the undivided peak (obtained from CFSE-labeled donor cells) are labeled 1–7 and 8+. Though rates of proliferation trended higher in SD→Rag samples, t test of cells in the undivided (Undiv) peak between HC and SD was p = 0.06 (n = 3–4), and no other differences were significant.
Tables
- Table 1.
Microglial M1/M2 phenotype is differentially altered by chronic stress exposure in donor mice and by the source of stressed cells in Rag2−/− recipient mice
Gene: treatment HC SD HC→Rag SD→Rag Sal→Rag IL-1β Media 1.10 ± 0.22 2.39 ± 0.28* 1.39 ± 0.46 0.78 ± 0.19 1.50 ± 0.06 IL-4 1.67 ± 0.23 1.51 ± 0.29 0.88 ± 0.17 0.92 ± 0.16 0.84 ± 0.13 LPS 7.15 ± 0.96*** 20.4 ± 3.31***# 8.95 ± 0.80*** 5.16 ± 0.93*** 7.32 ± 1.62*** IL-6 Media 1.06 ± 0.16 2.73 ± 0.26*** 2.02 ± 0.27** 1.33 ± 0.16 1.74 ± 0.16* IL-4 0.94 ± 0.15 1.92 ± 0.54 2.20 ± 0.41 1.64 ± 0.19 1.71 ± 0.17 LPS 6.20 ± 1.04*** 13.7 ± 1.72***# 17.6 ± 2.14***# 7.82 ± 0.91*** 23.8 ± 1.92***# MRC1 Media 1.03 ± 0.15 0.6 ± 0.08 0.54 ± 0.09*** 1.14 ± 0.15 0.65 ± 0.05 IL-4 1.74 ± 0.39 1.61 ± 0.44 0.76 ± 0.12 1.41 ± 0.22 0.73 ± 014 LPS 0.83 ± 0.18 0.67 ± 0.12 0.36 ± 0.08***# 0.62 ± 0.13 0.64 ± 0.08 ARG1 Media 1.04 ± 0.14 0.87 ± 0.25 0.56 ± 0.05 2.05 ± 0.22 1.16 ± 0.21 IL-4 22.0 ± 2.51*** 9.13 ± 1.63***# 2.98 ± 0.44***# 4.81 ± 0.78***# 2.33 ± 0.41***# LPS 1.33 ± 0.33 1.12 ± 0.17 1.12 ± 0.27 2.46 ± 0.96 1.23 ± 0.36 Group % of viable cells % of CD3+ cells % of CD4+ cells CD3+ CD19+ CD4+ CD8+ CD25+ Spleen HC→Rag 11.1 ± 0.9 2.3 ± 0.3 36.3 ± 0.8 58.2 ± 1.4 6.1 ± 1.3 SD→Rag 11.4 ± 1.7 1.9 ± 0.4 36.9 ± 2.6 59.0 ± 2.5 7.3 ± 0.9 Sal→Raga 0.3 ± 0.1 0.1 ± 0.1 0 0 0 Blood HC→Rag 18.6 ± 4.7 0.1 ± 0.0 46.1 ± 5.7 42.0 ± 8.6 0.7 ± 0.4 SD→Rag 21.4 ± 2.9 0.3 ± 0.1 47.1 ± 5.4 42.8 ± 5.3 0.9 ± 0.1 Sal→Raga 0.3 ± 0.3 0.1 ± 0.1 0 0 0 ↵aLymphopenic mice had significantly less of each cell type compared to adoptive transfer groups (p < 0.01).
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