Figure 7. Genetic knockout of NFκB in astrocytes reduces gliosis and α-synuclein aggregation throughout the brain.
(A) Schematic illustration of the Cre-recombinase under control of the human glial fibrillary acidic protein promoter (hGFAP). Hemizygous GFAP-Cre mice were crossed with I kappa B kinase 2 (Ikk2)-loxP mice, which facilitated selective deletion of IKK2 in astrocytes and provided a cell-specific knockout of NF-κB in astrocytes. hGFAP-cre+/−/IKK2fl/fl (KO) or hGFAP-cre−/−/IKK2fl/fl (WT) animals were intranasally infected with WEEV or mock-infected (control) with saline and treated with anti-E1immunotherapy. (B-D) IHC images with high magnification 40X inset images of P129+ staining from infected hGFAP-cre−/−/IKK2fl/fl WT mice, (E-G) uninfected control hGFAP-cre+/−/IKK2fl/fl KO mice and (H-J) infected hGFAP-cre+/−/IKK2fl/fl KO mice. (K) Pathological scoring of multiple brain regions was performed at 8WPI to quantify the extent of P129+ aggregation in each treatment group. (*p<0.05, **p<0.005, n=6-8 per group).