Fig. 4: Overexpression of p11 in ependymal cells from depressive mice ameliorates disrupted PCP and CSF flow, as well as depression-like behaviors.
From: Ependymal cells-CSF flow regulates stress-induced depression
a SEM images and quantification of multidirectional cilia orientation in ependymal cells in the V–SVZ of lateral ventricle from conditional p11 knockout (p11 cKO; Tppp3-Cre x p11f/f) mice with Cre-dependent viral overexpression of AAV1-DIO-p11 (AAV_p11) or AAV1-DIO-eYFP (AAV_eYFP) into intracerebroventricularly (n = 11 for each group). Scale bar, 2 μm. b MRI images and quantification of CSF flow from p11 cKO with the expression of AAV_p11 or AAV_eYFP in ependymal cells (n = 7, p11 cKO+AAV_eYFP; n = 8, p11 cKO+AAV_p11). Scale bar, 850 μm. c–f Depression- and anxiety-like behaviors in WT and p11 cKO mice with viral overexpression of AAV_p11 in ependymal cells, as measured by immobility time in tail suspension test (TST, c), forced swim test (FST, d), the latency to feed in novelty suppressed feeding test (NSF, e), and the total travel distance in locomotor activity test (f) (n = 10, WT + AAV_eYFP and WT + AAV_p11; n = 14, p11 cKO+AAV_eYFP and p11 cKO+AAV_p11). g Quantification of CSF flow from constitutive p11 KO crossed to Tppp3-Cre [p11 KO (Tppp3); p11 KO x Tppp3-Cre] mice with viral overexpression of AAV_p11 or AAV_eYFP into intracerebroventricularly. h–f Depression-like behaviors in p11 KO (Tppp3) mice with viral overexpression of AAV_p11 or AAV_eYFP in ependymal cells, as measured by TST (h), FST(i), NSF(j), and locomotor activity (k) (g–k, n = 8, p11 KO (Tppp3)+AAV_eYFP; n = 9, p11 KO (Tppp3)+AAV_p11). l Quantification of CSF flow from chronic stressed Tppp3-Cre [RST(Tppp3)] mice with viral overexpression of AAV_p11 or AAV_eYFP into intracerebroventricularly. (n = 5, RST(Tppp3)+AAV_eYFP; n = 8, RST(Tppp3)+AAV_p11). m–p Depression-like behaviors in WT and p11 KO (Tppp3) mice with viral overexpression of AAV_p11 in ependymal cells, as measured by TST (m), FST(n), NSF (o), and locomotor activity (p) (n = 8, RST(Tppp3)+AAV_eYFP; n = 7, RST(Tppp3)+AAV_p11). *P < 0.05 and ***P < 0.001, Student’s t-test. *P < 0.05 and **P < 0.01, ANOVA test. Data are mean ± s.e.m.
