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Fig. 5 | Molecular Neurodegeneration

Fig. 5

From: NF-κB is a critical mediator of post-mitotic senescence in oligodendrocytes and subsequent white matter loss

Fig. 5

Genes associated with stress responses and cellular senescence are upregulated upon NF-κB activation in OLs. a and b Heatmaps indicate significantly elevated gene signatures indicative for stress responses (a) and cellular senescence (b) in IKK2-CAPLP−CreERT2 O4+ OLs compared to control OLs at 3 and 20 wpi. c and d X-gal staining revealed significantly increased senescence associated ß-galactosidase activity in freshly isolated IKK2-CAPLP−CreERT2 O4+ OLs at 3 wpi. Blue X-gal positive cells are indicated by black arrows (Control: 2.1% ± 0.67% X-gal positive cells, IKK2-CAPLP−CreERT2: 28.1% ± 3.05% x-gal positive cells, n = 3). e Primary O4+ OLs isolated from IKK2-CAPLP−CreERT2 mice show senescence associated cell morphology as they adopt a larger and flattened morphology. f and g IKK2-CAPLP−CreERT2 O4+ OLs show an overall increased metabolic activity as oxidative phosphorylation (F, OCR normalized to control; IKK2-CAPLP−CreERT2: 150.2 ± 11.9%, n = 3–4) as well as glycolysis (G, ECAR normalized to control; IKK2-CAPLP−CreERT2: 132.3 ± 8.3%, n = 3–4) is significantly increased. h NF-κB activation in O4+ OLs leads to an increase in phosphorylated eIF2α indicating activation of the integrated stress response as revealed by western blot analysis at 3wpi. Prominent IKK2 and GFP reporter gene expression confirm transgene activation in IKK2-CAPLP−CreERT2 cells. i Quantification of h (n = 5). Data are shown as mean ± SEM. Grey bars, control; red bars, IKK2-CA.PLP−CreERT2. Statistical analysis: Two-tailed Mann–Whitney-U Test, (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 NS, non-significant (p > 0.05))

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