期刊
AGING CELL
卷 20, 期 6, 页码 -出版社
WILEY
DOI: 10.1111/acel.13387
关键词
aging; behavior; chronic stimulation; cognition dysfunction; endocrinology; mouse models; neural stem cells; Notch
资金
- National Natural Science Foundation of China [81901380, 81500930, 81701192]
- Natural Science Foundation of Shandong Province [ZR2017BC047, ZR2014HQ014, ZR2017BH078]
- Projects of Medical and Health Technology Development Program of Shandong Province [2019WS329]
- Scientific Research Foundation of Binzhou Medical University [BY2016KYQD21, BY2018KJ21]
Recent research has uncovered a potential link between adipose tissue and the hippocampus through the Adiponectin-Notch pathway, impacting hippocampal neurogenesis and cognitive function. Chronic stress can inhibit this pathway, leading to impaired hippocampal neurogenesis and cognitive dysfunction, but exercise and AdipoRon can reverse these effects.
A substantial percentage of late-life depression patients also have an cognitive impairment, which severely affects the life quality, while the co-occurring mechanisms are still unclear. Physical exercise can ameliorate both depressive behaviors and cognitive dysfunction, but the molecular mechanisms underlying its beneficial effects remain elusive. In this study, we uncover a novel adipose tissue to hippocampus crosstalk mediated by Adiponectin-Notch pathway, with an impact on hippocampal neurogenesis and cognitive function. Adiponectin, an adipocyte-derived hormone, could activate Notch signaling in the hippocampus through upregulating ADAM10 and Notch1, two key molecules in the Notch signaling. Chronic stress inhibits the Adiponectin-Notch pathway and induces impaired hippocampal neurogenesis and cognitive dysfunction, which can be rescued by AdipoRon and running. Inhibition Notch signaling by DAPT mimics the adverse effects of chronic stress on hippocampal neurogenesis and cognitive function. Adiponectin knockout mice display depressive-like behaviors, associated with inhibited Notch signaling, impaired hippocampal neurogenesis and cognitive dysfunction. Physical exercise could activate Adiponectin-Notch pathway, and improve hippocampal neurogenesis and cognitive function, while deleting adiponectin gene or inhibiting Notch signaling blocks its beneficial effects. Together, our data not only suggest that Adiponectin-Notch pathway is involved in the pathogenesis of cognitive dysfunction associated with depression, but also contributes to the therapeutic effect of physical exercise. This work helps to decipher the etiology of cognitive impairment associated with depression and hence will provide a potential innovative therapeutic target for these patients.
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