Fig. 8: Inhibition of GR signaling in the LH prevents PSS-induced maladaptive behaviors. | Nature Communications

Fig. 8: Inhibition of GR signaling in the LH prevents PSS-induced maladaptive behaviors.

From: Lateral hypothalamic proenkephalin neurons drive threat-induced overeating associated with a negative emotional state

Fig. 8

a Schematics for drug microinfusions before PSS exposure. b Images show locations of cannula tips in the LH. Arrowheads denote the end of tips, replicated independently with similar results in 4 mice. Scale bars, 500 μm. c, d 2.5 h food consumption 24 h after exposure to either control or PSS (n = 6, 8, 5, and 7 mice). In (c), one-way ANOVA (F(3,22) = 11.778, p < 0.001) was followed by Fisher LSD post hoc test for multiple comparisons; ***p < 0.001 compared with veh-injected control mice; †p = 0.041, †††p < 0.001 compared with veh-injected PSS mice; ##p = 0.008 compared with Mife (10 ng/side)-injected PSS mice. e Locations of the injection cannula tips in the mice included in (c, d). f–h Experimental procedure to test CPA (f). Time spent (%) of veh- (g; n = 8 mice) and Mife-treated mice (h; n = 6 mice) in PSS-paired chambers during pre- and post-test. Box–whisker plots display median (center) and 2.5 to 97.5 percentiles of the distribution (bounds) with whiskers extending from min to max values. In (g), two-tailed paired t test, t7 = 4.380, **p = 0.00324. In (h), two-tailed paired t test, t5 = 0.476, p = 0.654. i Schematic for the bilateral injection of AAV-DIO-eGFP, followed by implantation of cannula into the LH of Penk-Cre mice, replicated independently with similar results in 5 mice. Scale bar, 200 μm. j Representative images showing c-fos immunoreactivity and eGFP in the LH in response to either NC or HFD 24 h after PSS exposure. White arrowheads indicate the colocalization of c-fos with Penk expression, replicated independently with similar results in 5 mice. Scale bars, 20 μm. k Quantification of the proportion of c-fos-positive cells among LHPenk neurons in (j) (n = 5, 7, and 5 mice per group). One-way ANOVA (F(2,14) = 71.860, p < 0.001) was followed by Fisher LSD post hoc test for multiple comparisons; ***p < 0.001, †††p < 0.001 compared with veh-treated PSS mice after HFD exposure. n.s not significant. Data are expressed as mean ± SEM.

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