Modulation of microglia and presynaptic protein expression after mesenchymal stem cells treatment in a rat model of Alzheimer's disease

Abstract

Objectives: Sporadic Alzheimer´s disease (sAD) is the most prevalent neurodegenerative pathology with no effective therapy until date. This disease prompts hippocampal degeneration, which in turn affects multiple cognitive domains and daily-life activities. In this study, we hypothesized that long-lasting therapy with human mesenchymal stem cells (MSC) would have a restorative effect on the behavioral alterations and cognitive decline characteristic of sAD, as they have shown neurogenic and immunomodulatory activities.Methods: We treated intracerebroventricular streptozotocin-injected (icv-STZ) rats, a commonly used animal model of sAD, with 1 × 106 MSC in a tail vein (24 days post-icv-SZT), every 18 days. At the end of the study (3 months post-icv-STZ), we evaluated their cognitive function together with morphological and biochemical changes in the hippocampus.Results: We observed cognitive deficits, microgliosis, and decreased on presynaptic proteins (SYT1, SYT2, and SYP) and GABAergic neuron marker (GAD65) in the brains of icv-STZ rats. Interestingly, MSC therapy significantly improved its spatial memory and decreased the anxiety, ameliorated microglial activation, and enhanced SYT1, SYP, and GAD65 levels. Additionally, we found significant negative correlation between the hippocampal reactive microglia with the expression of SYT1, SYT2, SYP, and GAD67 proteins, suggesting the modulation of synaptic transmission by glial cells.Conclusion: These findings, showing that intravenous injection of human MSCs restores behavioral and hippocampal alterations in experimental sAD, support the potential use of MSC therapy for the treatment of neurodegenerative diseases.