Prominent stress response of Purkinje cells in Creutzfeldt-Jakob disease

To examine the role of stress-related 70-kDa heat shock proteins (Hsp-s) in Creutzfeldt-Jakob disease (CJD), we performed immunocytochemistry to detec t Hsp-72 and Hsp-73, together with the abnormal (PrPSc) and the presumed ce llular form (PrPC) of the prion protein, and TUNEL method to measure cellul ar vulnerability in different brain regions in CJD and control cases. While Hsp-73 showed uniform distribution in all the examined samples, an increas e in the number of Purkinje cells with prominent accumulation of Hsp-72 in the CJD group was observed. These neurons also showed intense PrPC staining , but TUNEL-positive nuclei were only detected in the granular (Hsp-72-nega tive) cell layer. Fewer cells of the inferior olivary nucleus were immunore active for Hsp-72 in CJD than in control cases, and regions showing severe spoongiform change and gliosis exhibited fewer Hsp-72-immunoreactive neuron s. Our results indicate that accumulation of the inducible Hsp-72 in certai n cell types may be part of a cytoprotective mechanism, which includes pres ervation of proteins like PrPC. (C) 2001 Academic Press.