Modulation of microglia and presynapticprotein expression after mesenchymal stemcells treatment in a rat model of Alzheimer?sdisease

ZAPPA VILLAR, MF; MOREL, GR; PARDO, J; REGGIANI, PC; LOPEZ HANOTTE, J; GARCÍA, MG

Daegu

Congreso; 10th IBRO World congress of Neuroscience; 2020

International Brain Research Organization

Objectives: Sporadic Alzheimer?s disease (sAD) is the mostprevalent neurodegenerative pathology with no effective therapyuntil date. This disease prompts hippocampal degeneration,which in turn affects multiple cognitive domains and daily-lifeactivities. In this study, we hypothesized that long-lasting therapywith human mesenchymal stem cells (MSC) would havea restorative effect on the behavioral alterations and cognitivedecline characteristic of sAD, as they have shown neurogenic andimmunomodulatory activities.Methods: We treated intracerebroventricular streptozotocininjected(icv-STZ) rats, a commonly used animal model of sAD, with1×106 MSC in a tail vein (24 days post-icv-SZT), every 18 days. Atthe end of the study (3 months post-icv-STZ), we evaluated theircognitive function together with morphological and biochemicalchanges in the hippocampus.Results: We observed cognitive deficits, microgliosis, anddecreased on presynaptic proteins (SYT1, SYT2, and SYP) andGABAergic neuron marker (GAD65) in the brains of icv-STZ rats.Interestingly, MSC therapy significantly improved its spatial memoryand decreased the anxiety, ameliorated microglial activation,and enhanced SYT1, SYP, and GAD65 levels. Additionally, we foundsignificant negative correlation between the hippocampal reactivemicroglia with the expression of SYT1, SYT2, SYP, and GAD67 proteins,suggesting the modulation of synaptic transmission by glialcells.Conclusion: These findings, showing that intravenous injectionof human MSCs restores behavioral and hippocampal alterations inexperimental sAD, support the potential use of MSC therapy for thetreatment of neurodegenerative diseases.