The ion channel TRPM4 in murine experimental autoimmune encephalomyelitis and in a model of glutamate-induced neuronal degeneration

Molecular Brain
Beatrice BianchiHugues Abriel

Abstract

Transient receptor potential melastatin member 4 (TRPM4), a Ca2+-activated nonselective cation channel, has been found to mediate cell membrane depolarization in immune response, insulin secretion, cardiovascular diseases, and cancer. In murine experimental autoimmune encephalomyelitis (EAE), TRPM4 deletion and administration of glibenclamide were found to ameliorate clinical symptoms and attenuate disease progression. However, the exact role of TRPM4 in EAE, as well as the molecular mechanisms underlining TRPM4 contribution in EAE, remain largely unclear. In the present study, EAE was induced in WT C57BL/6 N mice using myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) and TRPM4 protein and mRNA expression were examined in spinal cord membrane extracts. Our results showed that TRPM4 protein and mRNA are upregulated in EAE, and that their upregulation correlated with disease progression. Moreover, newly-developed TRPM4 inhibitors, named compound 5 and compound 6, were shown to exert a better neuroprotection compared to currently used TRPM4 inhibitors in an in vitro model of glutamate-induced neurodegeneration. These results support the hypothesis that TRPM4 is crucial from early stages of EAE, and suggest that these more pote...Continue Reading

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Citations

May 11, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Yi GongFei Wang
Apr 4, 2021·International Journal of Molecular Sciences·Lijo Cherian OzhathilHugues Abriel
Aug 3, 2021·Frontiers in Pharmacology·Prakash ArullampalamHugues Abriel
Aug 13, 2021·Neural Regeneration Research·Iván Alquisiras-BurgosPenélope Aguilera

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Methods Mentioned

BETA
transfection
Assay
PCR

Software Mentioned

GraphPad Prism
Image Studio Lite
GraphPad
Stata

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