First Trimester Human Umbilical Cord Perivascular cells (HUCPVC) Modulate the Kynurenine Pathway and Glutamate Neurotransmission in an LPS-induced Mouse Model of Neuroinflammation

Abstract

Abstract Background The Kynurenine Pathway (KP) of tryptophan degradation and glutamate toxicity is implicated in several neurological disorders, including depression. Although mesenchymal stromal cells (MSC)-mediated immunomodulation and neuroprotection have been studied in many of these disorders, their potential to influence KP and the glutamatergic system has not yet been investigated. Hence, this study sought to investigate the effect of HUCPVC, a rich and potent source of MSC, on Lipopolysaccharide (LPS)-activated KP metabolites, KP enzymes, and key components of glutamate neurotransmission. Methods The immunomodulatory effect of peripherally administered HUCPVC on the expression profile of kynurenine pathway enzymes and metabolites was assessed in the plasma and brain of mice treated with LPS. An assessment of the glutamatergic system, including selected receptors, transporters and proteins was also conducted. Results HUCPVC were found to modulate LPS-induced activation of KP enzymes and metabolites in the brain associated with neurotoxicity. Moreover, the reduced expression of the glutamatergic components due to LPS was also found to be significantly improved by HUCPVC. Conclusions The immunomodulatory properties of HUCPVC appear to confer neuroprotection, at least in part, through their ability to modulate the KP in the brain. This KP modulation enhances neuroprotective regulators and downregulates neurotoxic consequences, including glutamate neurotoxicity, which is associated with neuroinflammation and depressive behavior.