Stereotaxic Delivery of M1000 Prions to the Hippocampus Induces Related Behavioural and Cognitive Changes Consistent with Acute Neurotoxic Effects

Abstract

Prion diseases are fatal neurodegenerative disorders characterised by the misfolding of the normal prion protein (PrPc) into a pathogenic isoform (PrPSc), with the latter constituting the predominant or possibly only component of infectious prions. While ongoing PrPSc propagation and accumulation appear central pathophysiological features underpinning disease progression, whether PrPSc harbours direct acute neurotoxic effects in vivo has been under-investigated. In this study, we aimed to investigate the hypothesis that PrPSc in sufficient quantity can induce acute neurotoxicity in vulnerable brain regions independent of significant net transmitting PrPSc replication. Using the M1000 prion m..