Fig. 3

IL-6 reduces αSyn pathology in wild type mice following intra-hippocampal injection of αSyn aggregates. Neonatal wild type mice were injected with rAAV-EV or rAAV-IL-6 and subsequently bilaterally injected in the hippocampus with αSyn fibrils at 2 months of age. Mice were analyzed 4 months post injection with αSyn fibrils in the hippocampus. Representative images of different brain regions stained with two antibodies (EP1536Y and 81A) that recognize the pSer129 epitope on αSyn are shown (a–b). The pattern and distribution of pSer129 αSyn pathology was similar with both antibodies. αSyn inclusions were mainly found in the hippocampus, dentate gyrus and cortical regions. Mice expressing IL-6 presented with lower levels of αSyn pathology than in EV control cohorts. Hematoxylin was used to counterstain tissues. Scale Bar, 25 μm. Red dots depicting rostral/caudal distribution of αSyn inclusions in wild type mice identified by pSer129 immunostaining is presented as a qualitative measure of relative amounts of αSyn burden (c). The actual number of αSyn inclusions were counted in EP1536Y stained sections (whole brain) of IL-6 and EV cohorts injected with αSyn aggregates (d). **p < 0.01. e–f, Co-immunofluorescence staining with GFAP (astrocyte marker, Alexa Fluor 594) or NeuN (neuronal marker, Alexa Fluor 594) with 81A antibody (Alexa Fluor 488) shows αSyn inclusions primarily localized in the neurons in the hippocampus (arrows, e) and cortex (arrows, f). Overall, intraneuronal αSyn inclusion pathology is reduced in IL-6 expressing mice. n = 4–5 mice/cohort. Scale bar, 25 μm