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. 2021 May 12;41(19):4172–4186. doi: 10.1523/JNEUROSCI.2539-20.2021

Figure 5.

Figure 5.

Microglial BDNF deficiency supports newborn immature neuron survival and reduces microglial proliferation following LPS infection. A, Experimental timeline for intraperitoneal BrdU injection following intrahippocampal LPS administration in Cx3cr1creERT2 x Bdnf flox/flox mice. B, Representative images of DCXpos and DCXposBrdUpos immature neurons in the dentate gyrus. Scale bar, 50 μm. Dotted lines indicated the GCL. C, Quantification of DCXpos immature neurons 7 d after intrahippocampal LPS injection (F(2,19) = 18.98, p < 0.0001). D, Quantification of newly born DCXposBrdUpos immature neurons that were born 1–4 d after LPS stimulation and survive until day 7 post-LPS (F(2,19) = 47.39, p < 0.0001). E, Representative confocal images of IBA1posBrdUpos microglia in the dentate gyrus. Scale bar, 50 μm. F, Quantification of IBA1pos microglia in the dentate gyrus (F(2,24) = 76.99, p < 0.0001). G, Quantification of IBA1posBrdUpos microglia in the dentate gyrus (F(2,19) = 11.87, p = 0.0005). H, Quantification of IBA1pos mean fluorescence intensity (F(2,15) = 28.31, p < 0.0001). I, Representative confocal images of Tmem119pos, CD68pos microglia in the dentate gyrus. J, K, Quantification of TMEM119pos (J: F(2,16) = 3.73, p = 0.047) and CD68pos (K: F(2,16) = 2.17, p = 0.15) mean fluorescence intensity. L, Experimental timeline for Cx3cr1creERT2 x Bdnf flox/flox killed 6 h after intrahippocampal LPS administration. M, qPCR data for select genes associated with the neuroinflammatory response to LPS infection in the ipsilateral hippocampus of Cx3cr1creERT2 x Bdnf flox/flox mice 6 h after saline or LPS injection. Expression is relative to the Hprt housekeeping gene and presented as the “fold change” from saline-injected corn oil-gavaged vehicle controls (Ccl2: F(2,10) = 11.70, p = 0.0024; Csf-1: F(2,10) = 12.56, p = 0.0019; IL-1β: F(2,10) = 77.99, p < 0.0001; IL-6: F(2,10) = 4.87, p = 0.033; IL-10: F(2,10) = 3.88, p = 0.035; TNF-α: F(2,10) = 5.08, p = 0.030, n = 3–5/group). Data represent the mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Statistical tests: one-way ANOVA followed by Bonferroni post hoc comparison; asterisks indicate post hoc results (C, D, F–H, J, K, M). Small circles represent individual mice. A.U., Arbitrary units.