Fig. 5: Downregulation of astrocytic Fgf2 in the NAc increases stress susceptibility and blunts physical exercise benefits. | Nature Communications

Fig. 5: Downregulation of astrocytic Fgf2 in the NAc increases stress susceptibility and blunts physical exercise benefits.

From: Environmental enrichment and physical exercise prevent stress-induced social avoidance and blood-brain barrier alterations via Fgf2

Fig. 5: Downregulation of astrocytic Fgf2 in the NAc increases stress susceptibility and blunts physical exercise benefits.

A Experimental timeline for AAV5-gfaABC1D-shRNA bilateral injection in the NAc. Mice were injected and 4 weeks later, NAc brain tissues were collected. B Mice injected with AAV5-shRNA-mFgf2 virus have lower Fgf2 signal intensity in astrocytes compared to controls AAV5-GFP (representative images of NAc infected area on the left, scalebar = 2 mm, and cell specificity on the right, scalebar = 50 μm with 25 μm for high magnification images below). C Experimental timeline for AAV5-gfaABC1D-shRNA bilateral injection in the NAc, followed by chronic social defeat stress (CSDS), then Social Interaction (SI) test. D SI ratio is lower for stressed mice with downregulation of astrocytic Fgf2 in the NAc. AAV5-gfaABC1D-shRNA-mFgf2 mice from the stressed group display higher susceptibility compared to AAV5-gfaABC1D-shRNA-scramble stressed mice (E) but no difference in locomotion (F). G Experimental timeline for AAV5-gfaABC1D-shRNA bilateral injection in the NAc, followed by CSDS with access to running wheels, then SI test prior tissue collection. H Chronic social stress promotes social avoidance as measured by lower SI ratio and increased number of entries in the corners in both AAV5-gfaABC1D-shRNA-mFgf2- and AAV5-gfaABC1D-shRNA-scramble-injected mice (I) and this is not related to locomotion impairment (J). K Running distance increases across days for mice injected with the control virus but not for AAV5-gfaABC1D-shRNA-mFgf2-injected animals (L). The dotted line is set at maximum running distance during the first 24 h. M After CSDS, AAV5-gfaABC1D-shRNA-mFgf2 mice show lower levels of Fgf2 mRNA without or with access to physical exercise (PE), compared to mice injected with control AAV5-gfaABC1D-shRNA-scramble virus. PE also elevates Fgf2 in this group. Data represent mean ± s.e.m., the number of animals is indicated on graphs. Group comparisons were evaluated with one- or two-way ANOVA followed by Bonferroni’s post hoc tests, or two-tailed t-tests with Welch’s correction; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

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