Transplantation of platelet-derived mitochondria alleviates cognitive impairment and mitochondrial dysfunction in db/db mice

Diabetes-associated cognitive impairment (DACI) can increase the risk of major cardiovascular events and death. Neuronal functionality is highly dependent on mitochondria and emerging evidence has shown that mitochondrial transplantation is a potential and effective strategy that can reduce brain injury and associated disorders. Platelets are abundant in blood and can be considered a readily available source of small-size mitochondria. These cells can be easily acquired from the peripheral blood with minimal invasion via simple venipuncture. The present study aimed to investigate whether transplantation of platelet-derived mitochondria (Mito-Pit) could improve DACI. Cognitive behaviors were assessed using the Morris water maze test in db/db mice. The results demonstrated that Mito-Plt was internalized into hippocampal neurons 24 h following intracerebroventricular injection. Importantly, one month following Mito-Plt transplantation, DACI was alleviated in db/db mice and the effect was accompanied with increased mitochondrial number, restored mitochondrial function, attenuated oxidative stress and neuronal apoptosis, as well as decreased accumulation of A beta and Tau in the hippocampus. Taken together, the data demonstrated that transplantation of Mito-Pit attenuated cognitive impairment and mitochondrial dysfunction in db/db mice. This method may be a potential therapeutic application for the treatment of DACI.