Complement factors alter the amount of PrPSc in primary-cultured mouse cortical neurons associated with increased membrane permeability

We examined the effects of complement factors on primary-cultured neurons infected with prions. The amount of protease K (PK)-resistant abnormal form of prion protein (PrPSc) reached a maximum level at 12 and 16 days post exposure (dpe) in 22L- and Chandler-infected neurons, respectively. In Chandler-infected neurons, the reaction of complement factors C1q, C3 and C9 significantly increased membrane permeability. This was followed by a decrease of PK-resistant PrPSc at 16 and 20 dpe. In contrast, in 22L-infected neurons, the effects of complement factors were observed at 12 and 16 dpe, but not at 20 dpe. Membrane permeability also increased in 22L-infected neurons by reaction of complement factor C3, but interestingly, the amount of PK-resistant PrPSc initially decreased, and then increased. These results suggest that the reactivity of complement factors in prion-infected neurons depends on the amount of PrPSc and the prion strain.