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. 2024 Mar 30;14:170. doi: 10.1038/s41398-024-02877-0

Fig. 2. CB2R inhibition in combination with PE ameliorates chronic stress-induced negative impacts in AHN.

Fig. 2

a Chronic stress decreases the total number of proliferating (Ki67+) cells, particularly evident in the vHip, and AM630 treatment in combination with PE significantly rescues this deficit. Cell counts of Ki67+ cells per total (a1), dorsal (a2), and ventral (a3) estimated volumes are depicted. b Chronic stress decreases the number of proliferating neuroblasts (Ki67+DCX+), and AM630 treatment in combination with PE counteracts the stress-induced detrimental effect. Cell counts of Ki67+DCX+ cells per total (b1), dorsal (b2), and ventral (b3) estimated volumes are depicted. c The pool of immature neurons (DCX+) is diminished by uCMS, an effect countered by PE alone or in combination with AM630 treatment in combination and particularly evident in the vHip. Cell counts of DCX+ cells per total (c1), dorsal (c2), and ventral (c3) estimated volumes are depicted. d Representative images of coronal sections of dHip and vHip of all tested conditions, depicting cells stained for DCX (green), Ki67 (red) and DAPI (blue) with magnified boxed areas showing the detailed expression of individual markers in each condition; scale bars = 50 µm. e Chronic stress significantly impairs the survival of newborn neurons (BrdU+NeuN+), an effect prevented by AM630 treatment in combination with PE, particularly evident in the vHip. Cell counts of BrdU+NeuN+ cells per total (e1), dorsal (e2), and ventral (e3) estimated volumes are depicted. f Representative images of coronal sections of dHip and vHip of all tested conditions, depicting cells stained for BrdU (green), NeuN (red), and DAPI (blue) with magnified boxed areas showing the detailed expression of individual markers in each condition; scale bars = 50 µm. Data presented as mean ± SEM and circles represent individual data points (animals) [Student’s t test: ****p < 0.0001, ***p < 0.001, **p < 0.01 vs CTRL; Two-way ANOVA: ###p < 0.001, ##p < 0.01, #p < 0.05 vs uCMS; further statistical details in Table S4]. uCMS unpredictable chronic mild stress, AM630 CB2R inverse agonist, PE physical exercise.