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Hippocampal Mitochondrial Transplantation Alleviates Age-Associated Cognitive Decline via Enhancing Wnt Signaling and Neurogenesis
Zhaoyichun Zhang 1, Di Wei 2, Zijie Li 3, Hanfeng Guo 3, Yin Wu 2, Jianying Feng 1
...In the present study, we transplanted mitochondria isolated from young mice into the hippocampus of aged mice, which presumably boost mitochondrial function more thoroughly, examined the effects on cognition, and explored the possible underlying mechanism. Our data showed that exogenous mitochondria were efficiently internalized by nestin-positive neural progenitors in the hippocampus. Mitochondrial transplantation quickly increased ATP levels, enhanced the activity of mitochondrial complexes I, II, and IV, and decreased Tom20 expression in the hippocampus. In regard of cognitive function, mitochondria-treated mice displayed a remarkable improvement of novel object recognition and spatial memory. Utilizing the Wnt signaling reporting mouse line, TOPGAL mice, we detected activated canonical Wnt signaling in the neural progenitors of the mitochondria-treated hippocampus. Further, BrdU labeling showed that exogenous mitochondria significantly stimulated neural progenitor neurogenesis and proliferation. Taken together, our data demonstrated that exogenous mitochondria from young mice might be a novel way of rejuvenating the function of hippocampal neural progenitors to exert antiaging effects.