Sphingosine-1-Phosphate Receptors Modulators Decrease Signs of Neuroinflammation and Prevent Parkinson's Disease Symptoms in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model

Frontiers in Pharmacology
Élise PépinMichel Cyr

Abstract

Sphingosine-1-phosphate (S1P) is a potent bioactive lipid mediator that acts as a natural ligand upon binding to five different receptors that are located in astrocytes, oligodendrocytes, microglial and neuronal cells. Recently, global activation of these receptors by FTY720 (fingolimod) has been suggested to provide neuroprotection in animal model of Parkinson's disease (PD). Among S1P receptors, the subtype 1 (S1P1R) has been linked to features of neuroprotection and, using the selective agonist SEW2871, the present investigation assessed potential benefits (and mechanisms) of this receptor subtype in an established animal model of PD. We demonstrated that oral treatments with SEW2871 are able to provide protection to the same levels as FTY720 against loss of dopaminergic neurons and motor deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg, i.p., 5 days) mouse model of PD. At the molecular level, we observed that the beneficial effects of both S1PR agonists were not associated with alterations in ERK and Akt levels, two markers of molecular adaptations in the striatum neurons. However, these compounds have the capacity to prevent signs of neuroinflammation such as the activation of astrocytes and gl...Continue Reading

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Citations

Oct 3, 2020·International Journal of Molecular Sciences·Eileen M McGowanYiguang Lin
Feb 21, 2021·Molecular Neurobiology·Efthalia AngelopoulouChristina Piperi
May 20, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Edzard SchwedhelmChi-Un Choe
Jul 3, 2021·International Journal of Molecular Sciences·Joanna A MotylRobert P Strosznajder
Aug 8, 2021·International Journal of Molecular Sciences·Bhakta Prasad Gaire, Ji-Woong Choi

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Methods Mentioned

BETA
electrophoresis
dissector
transgenic

Software Mentioned

Graph Pad
ImageJ
VisionWorks LS
Stereo Investigator
GraphPad Prism

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