Akebia saponin D acts via the PPAR‐gamma pathway to reprogramme a pro‐neurogenic microglia that can restore hippocampal neurogenesis in mice exposed to chronic mild stress

• DOI: 10.1111/cns.14196
• Publication Date: 2023-03-29T07:26:34Z
• Authors: Jinqiang Zhang; Qin Liu; Dapeng Su; Liangyuan Li; Chenghong Xiao; Hui He; Zili You; Tao Zhou
• Keywords: PPAR gamma; Mice, Inbred C57BL; Mice; 0303 health sciences; 03 medical and health sciences; Brain-Derived Neurotrophic Factor; Neurogenesis; Animals; Original Articles; Microglia; Hippocampus; 3. Good health

Abstract Background Using drugs to modulate microglial function may be an effective way treat disorders, such as depression, that involve impaired neurogenesis. Akebia saponin D (ASD) can cross the blood–brain barrier and exert anti‐inflammatory neuroprotective effects, so we wondered whether it might influence adult hippocampal neurogenesis depression. Methods We exposed C57BL/6 mice chronic mild stress (CMS) a model of depression then gave them ASD intraperitoneally once daily for 3 weeks. investigated effects on phenotype, neurogenesis, animal behavior. The potential role peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) or BDNF–TrkB pathway in pro‐neurogenesis anti‐depressant was identified using there inhibitors GW9662 K252a, respectively. neurogenic ASD‐treated microglia were evaluated conditioned culture methods. Results found CMS upregulated pro‐inflammatory factors inhibited dentate gyrus mice, while inducing depressive‐like behaviors. Dramatically, (40 mg/kg) treatment reprogrammed arginase (Arg)‐1 + phenotype gyrus, which increased brain‐derived neurotrophic factor (BDNF) expression restored partially ameliorated behaviors CMS‐exposed mice. K252a inhibitor blocked pro‐neurogenic, ASD. Furthermore, activated PPAR‐γ well primary cultures treated with lipopolysaccharide. Blocking GW9962 suppressed ASD‐reprogrammed Arg‐1 BDNF Such blockade abolished promoted NSPC proliferation, survival, pro‐neurogenic by GW9962. Conclusion These results suggested acts via induce increase promote