Mesenchymal Stem Cell Protection of Neurons against Glutamate Excitotoxicity Involves Reduction of NMDA-Triggered Calcium Responses and Surface GluR1, and Is Partly Mediated by TNF

International Journal of Molecular Sciences
Irini PapazianL Probert

Abstract

Mesenchymal stem cells (MSC) provide therapeutic effects in experimental CNS disease models and show promise as cell-based therapies for humans, but their modes of action are not well understood. We previously show that MSC protect rodent neurons against glutamate excitotoxicity in vitro, and in vivo in an epilepsy model. Neuroprotection is associated with reduced NMDA glutamate receptor (NMDAR) subunit expression and neuronal glutamate-induced calcium (Ca2+) responses, and increased expression of stem cell-associated genes. Here, to investigate whether MSC-secreted factors modulate neuronal AMPA glutamate receptors (AMPAR) and gene expression, we performed longitudinal studies of enriched mouse cortical neurons treated with MSC conditioned medium (CM). MSC CM did not alter total levels of GluR1 AMPAR subunit in neurons, but its distribution, reducing cell surface levels compared to non-treated neurons. Proportions of NeuN-positive neurons, and of GFAP- and NG2-positive glia, were equal in untreated and MSC CM-treated cultures over time suggesting that neurons, rather than differentially-expanded glia, account for the immature gene profile previously reported in MSC CM-treated cultures. Lastly, MSC CM contained measurable amoun...Continue Reading

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Citations

Apr 9, 2020·Frontiers in Cellular Neuroscience·Denisa Belov KirdajovaMiroslava Anderova
Apr 4, 2019·Molecular Neurobiology·Eliana Baez-JuradoGeorge E Barreto
Feb 27, 2020·Case Reports in Psychiatry·Lauren NagyAnthony Tobia
Mar 13, 2020·Neurochemical Research·Yan YanHaibing Yu
Dec 24, 2020·International Journal of Molecular Sciences·Valentina SalariPaolo Francesco Fabene

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Software Mentioned

Cell R
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CellQuest
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