The role of glial cells in BSE pathology: a histomorphological and immunohistochemical investigation

Fast, Christine* GND; Santiago-Mateo, Kristina; Katoch, Rakhi; Groschup, Martin H. GND; Ziegler, Ute GND; Czub, Stefanie

Background/Introduction: Bovine spongiform encephalopathy (BSE) is a fatal neurological disease of cattle associated with the accumulation of an altered form of the cellular prion protein, termed pathological prion protein (PrPBSE) The pathomechanisms linking abnormal protein accumulation with the typical severe neurological alterations in BSE are less than clear. Here we investigated the role of glia cells in the pathology of BSE infected cattle, specifically if and to which degree the histopathological changes are glia mediated and therefore due to the host response and not to the BSE agent itself. Material and Methods: We examined 29 experimentally BSE infected cattle at preclinical (no PrPBSE in the brain stem), late preclinical (no clinical signs, first traces of PrPBSE in the brain stem), and clinical (clinical signs and distinct accumulation of PrPBSE in the brain stem) stages of the disease. The following defined regions of the CNS were examined: Obex, Red Nucleus, Cerebellum, Parietal Cerebrum, Septal Nucleus, and Hippocampus and both histopathological lesions and PrPBSE accumulation were determined. Additionally, antibodies Iba-1, CX3CR1, and GFAP were used to visualize and identify glial involvement within the context of the disease. In addition, four unchallenged animals of the same age groups were included as negative controls. Results: PrPBSE is found only in neurons and microglia. Different analytic approaches showed that the most consistent changes in glial numbers and phenotypes were detected in the Obex, Red Nucleus, and Hippocampus. However, only in clinical affected cattle, we observed with all antibodies a mild diffuse increase in glial reactivity, indicating a gliosis, as compared to controls, preclinical, and late preclinical animals. Additionally, different glial reaction patterns were almost exclusively detected in clinical animals. This includes a hyperplastic and in parts irregular appearance of the glial network, an accumulation of clumsy cells with shortened processes and rounded cell bodies, a diffusely distributed coarse granular staining and occasionally perineuronal cluster of glial cells. Conclusion: Apart from neurons, we identified microglia as the only other PrPBSE accumulating cell population; computerized assessment of IBA1, CX3CR1, and GFAP antibodies are ongoing. The preliminary results presented here indicate that the activation of a glial response is a rather late event, most probably associated with the accumulation of PrPBSE.

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Fast, Christine* / Santiago-Mateo, Kristina / Katoch, Rakhi / et al: The role of glial cells in BSE pathology: a histomorphological and immunohistochemical investigation. 2019.

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