Figure 4.

Elevated miR-155 reduces immature neuron survival and induces their ectopic localization in the GCL. A, miR-155 transgenic mouse experimental groups and study design. Comparison of control versus miR155-hi or miR155-hi versus miR155-lo determines whether embryonic and postnatal expression of miR-155 affects neural development and maturation. Comparison of miR155-lo versus miR155-hi-adult or control versus miR155-hi-adult determines whether expression of miR-155 only in the adult phase affects neurogenesis and microglial activation. In all groups in addition to control (e.g., mice expressing miR-155 transgene), a high level of miR-155 expression is induced by the removal of DOX in any cell previously expressing nestin. B, Representative images of DCX⁺ immature neurons in control, miR155-hi, miR155-lo, and miR155-hi-adult DG showing their miR-155-induced ectopic localization in the GCL. The SGZ is marked by dotted white line. Left images, 10× objective original magnification; right images, 40× original magnification. Scale bars, 100 μm. C, Quantification of total DCX⁺ cells in DG. D, Quantification of DCX⁺ cells in the SGZ per millimeter. E, Quantification of ectopically located DCX⁺ cells in the GCL per millimeter. n = at least 5 20× original magnification images per animal from 4 to 5 animals per group. ***p < 0.001, **p < 0.01, and *p < 0.05 as determined by 1-way ANOVA and Tukey post hoc. Data are shown as mean ± SEM.