Mesenchymal Stem Cell-Derived Extracellular Vesicles Suppresses iNOS Expression and Ameliorates Neural Impairment in Alzheimer's Disease Mice

Background: Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been reported to exhibit therapeutic effects in various animal models of neurological diseases, such as stroke and hypoxic-ischemic brain injury. Objective: The present study investigated the potential beneficial effect of MSC-derived EVs in an animal model of Alzheimer's disease (AD). Methods: APP/PS1 mice and their non-transgenic littermates (WT) received intracerebroventricle injection of MSC-derived EVs once per two days for two weeks. Then novel object recognition and water maze tasks were carried out to measure the cognitive behaviors. Electrophysiological tests were carried out to measure hippocampal synaptic plasticity. Inducible nitric oxide synthase (iNOS) mRNA and protein levels were measured by qRT-PCR and western blotting in primary cultured neurons treated with amyloid-beta peptide (A beta) or prepared from APP/PS1 mice. Results: Treatment with MSC-derived EVs alleviates exogenous A beta-induced iNOSmRNAand protein expression. In cultured primary neurons prepared from APP/PS1 pups, iNOS mRNA and protein levels were significantly reduced when treated with MSC-derived EVs. MSC-derived EVs improved cognitive behavior, rescued impairment of CA1 synaptic transmission, and long-term potentiation in APP/PS1 mice. Conclusion: MSC-derived EVs possessed beneficial effects in a mouse model of AD, probably by suppressing A beta induced iNOS expression.