Fig 2: A prospective model for clarifying the role and regulation of ATG5 and ATG7 on autophagy and ER stress. ATG5 and ATG7 induce autophagy, whereas repress ER stress and apoptosis through PERK signaling, one vital signal pathway of ER stress. “?” and “?” indicate activation and repression, respectively

Fig 3: Suppression of hippocampal neurogenesis, anxiety-like and depressive behaviors, and spatial memory deficits induced by CRS are prevented in Atg7-NSC cKO mice. (A) Timeline for the measurement of the number of BrdU+ and RBFOX3+ double-positive NSCs. (B) Representative images of BrdU+ RBFOX3+ staining. Scale bar: 20 µm. Arrow indicate RBFOX3+ BrdU+ double-positive cells. (C) Quantification of BrdU+ RBFOX3+-positive cells (n = 6 or 7 per group). (D and E) Measurement of anxiety-like behaviors by the open field test (n = 6 or 7 per group) (D) and elevated plus maze test (n = 6–13 per group) (E). (F) Measurement of depressive behavior by the sucrose preference test (n = 6). (G) Assessment of spatial working memory by the Y-maze test (n = 6–8 per group). (H) Spatial learning and memory test using the acquisition phase (left graph) and probe test at day 6 (right graph) in MWM test (n = 6–8 per group). TQ, target quadrant; AL, adjacent left; AR, adjacent right; OP, opposite. *P < 0.05, **P < 0.01, ***P < 0.001.

Fig 4: Autophagy in KCs was impaired in old mice after CCl4 treatmentA. Autophagy activation in KCs was detected by staining ATG7 by immunofluorescence assay. ATG7 was presented by green fluorescence, DAPI was used to stain nuclei(400×). B. LC3 I/II was tested by western blotting assay. Y, young; O, old; Y+C, young+CCl4; O+C, old+CCl4.

Fig 5: Chronic restraint stress (CRS)-induced reduction in the number of adult hippocampal NSCs is prevented by Atg7 deletion. (A) Scheme of mouse breeding and experimental time line for generation of tamoxifen (TAM)-inducible NSC-specific Atg7-NSC cKO mice. (B) Gene dose–dependence of ATG7 immunofluorescence intensities in the DG of the hippocampus. Scale bar: 50 µm. Solid and dotted circles indcate granule neurons and NSCs, respectively. The graph shows quantification of SOX2+ and ATG7+ cells (n = 6). (c) Timeline of the experiment. (D) Representative images of BrdU and SOX2 staining in the subgranular zone (SGZ) of the hippocampus. Scale bar: 20 µm. The graph on the right shows quantification of BrdU+ and SOX2+ cells (n = 6–8 per group). (E) Immunofluorescence of SOX2, NES and VIM in the SGZ of the DG of the hippocampus. Scale bar: 50 µm. Arrows indicate NSCs positive for each marker. ***P < 0.001 for the total SOX2+ cells. ###P < 0.001 for BrdU+ SOX2+ cells. n.s., not significant.