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

Abstract

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-Plt) 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 Aβ and Tau in the hippocampus. Taken together, the data demonstrated that transplantation of Mito-Plt attenuated cognitive impairment and mitochondrial dysfunction in db/db mice. This method may be a potential therapeutic application for the treatment of DACI.

Platelet Mitochondria Transplantation Rescues Hypoxia/Reoxygenation-Induced Mitochondrial Dysfunction and Neuronal Cell Death Involving the FUNDC2/PIP3/Akt/FOXO3a Axis

“…Consequently, platelets may be employed as mitochondrial donor cells 11 . In a recent study, delivery of plt-mito into the brain of diabetic mice restored hippocampal mitochondrial function and improved the cognitive ability 11 . Interestingly, FUNDC2 has been identified as a protein highly-expressed in the OMM of plt-mito, and offers significant protection against hypoxia-induced platelet apoptosis 12 .…”

“…Platelets are anucleate cells abundant in blood. Platelet collection by venous venipuncture is minimally-invasive 11 . More significantly, platelets contain small-size mitochondria and possess neuron-like biochemical properties 11 .…”

“…Platelet collection by venous venipuncture is minimally-invasive 11 . More significantly, platelets contain small-size mitochondria and possess neuron-like biochemical properties 11 . Consequently, platelets may be employed as mitochondrial donor cells 11 .…”

“…More significantly, platelets contain small-size mitochondria and possess neuron-like biochemical properties 11 . Consequently, platelets may be employed as mitochondrial donor cells 11 . In a recent study, delivery of plt-mito into the brain of diabetic mice restored hippocampal mitochondrial function and improved the cognitive ability 11 .…”

Extracellular Mitochondria Signals in CNS Disorders

“…Mitochondrial transplantation also improved diabetesassociated cognitive impairment (DACI) which is associated with elevated Aβ deposition (Ma et al, 2020). In this study, platelet-derived mitochondria were used as the donor source.…”