Prnp Deletion Mitigates Muscle Fiber Type-Specific Sarcopenia Induced by Prion Infection in Mice

Abstract

Recent studies have shown that significant expression of PrP^C protein is also present in skeletal muscle, and it plays a significant role in maintaining skeletal muscle homeostasis. Although the expression of PrP^C in skeletal muscle has been clarified, the effects of PrP^Sc-mediated prion protein infection on sarcopenia in mice and its potential regulatory mechanisms remain unclear. This study investigated the role of PrP^C in Prion-induced sarcopenia, using an animal model of prion disease based on intraperitoneal injection of the scrapie strain ME7 into wild-type mice and Prnp knockout mice. The results indicate that prion infection-induced sarcopenia exhibits muscle fiber type specificity, and that the lack of PrP^C can prevent prion protein infection-induced sarcopenia, although the lack of PrP^C may lead to reduced mitochondrial-endoplasmic reticulum homeostasis. These data provide novel evidence that prion infection affects skeletal muscle system health through myofiber-specific mechanisms.