Loss of oligodendrocyte transcription factor 2 protein expression in metabolically stressed oligodendrocytes.

Cuprizone intoxication in the presence of siponimod treatment also resulted in elevated Atf3 levels; however, this increase did not reach statistical significance (Fig. 9 d, h—Cortex: Ctrl 100% ± 31.66; 1 week Cup-Veh 571.6% ± 95.89; 1 week Cup-Sipo 469.3% ± 169.4; Corpus callosum: Ctrl 100% ± 27.6; 1 week Cup-Veh 1,196% ± 220.7; 1 week Cup-Sipo 826.3% ± 134.7).

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Regarding the ISR pathway, Atf3 showed a trend toward upregulation at 1 week in the array data (Fig. 9 a) and reached significance in the 3 week Cuprizone + Siponimod group (Fig. 9 b).

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