Cuprizone-induced demyelination in mGFAP-driven conditional transient receptor potential ankyrin 1 (TRPA1) receptor knockout mice
01/29/2020
Erika Pintér1, Gábor Kriszta1, Balázs Nemes1, Zoltán Sándor1, Péter Ács1, Sámuel Komoly1, Zoltán Berente1, Kata Bölcskei1, Erika Pintér1
1 Department of Pharmacology, Department of Neurology, Department of Biochemistry Medical SchoolUniversity of Pécs
Transient receptor potential ankyrin 1 (TRPA1) non-selective cation channels are mainly expressed by primary sensory neurons however, their expression by astrocytes and oligodendrocytes has recently been detected in the mouse brain. thse receptors are responsive to exogenous irritants and endogenous products of the oxidative stress. Genetic lack of TRPA1 attenuated the cuprizone-induced oligodendrocyte apoptosis and myelin loss in mice. In the present study we investigatied the effect of cuprizone feeding in mGFAP-driven conditional TRPA1 KO mice. Animals were generated by crossbreeding GFAP-Cre+/- and floxed TRPA1 (TRPA1Fl/Fl) mice. Cuprizone was administered during 6 weeks and demyelination was analysed by magnetic resonance imaging (MRI). At the end of the experiment histological investigation was also performed. MRI data showed that demyelination was reduced in both homozygous (GFAP-Cre-/- TRPA1Fl/Fl) and heterozygous (GFAP-Cre+/- TRPA1Fl/-) conditional knockout animals at weeks 3 and 4 of the treatment compared to the Cre-/- control mice. However, by week 6 of the treatment the difference was not shown by either MRI or histology. According to the present results we conclude that TRPA1 receptors on the GFAP positive cells modulate the cuprizoze-evoked demyelination however expression of TRPA1 by other cells in the brain can also participate in the pathological process.