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Behavioral and neuropathological changes have been widely investigated in murine prion disease but stereological based unbiased estimates of key neuropathological features have not been carried out. After injections of ME7 infected (ME7) or normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6, we assessed behavioral changes on hippocampal-dependent tasks. We also estimated by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total number of neurons, reactive astrocytes, activated microglia and perineuronal nets (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino Swiss mice. On average, early behavioral changes in albino Swiss mice start four weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data in albino Swiss mice revealed that four of nine subjects start to change their behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal degeneration, and stereological data showed that early astrocytosis, microgliosis and reduction in the perineuronal nets are independent of a change in the number of neuronal cell bodies. Statistical analysis revealed that the septal region had greater levels of neuroinflammation and extracellular matrix damage than CA1. This stereological and multivariate analysis at early stages of disease in an outbred model of prion disease provided new insights connecting behavioral changes and neuroinflammation and seems to be important to understand the mechanisms of prion disease progression.

The aim of this study was to determine the rationale, methodology, and progress of risk perceptions of laboratory workers in relation to existing prion disease infection control policies in Canadian medical laboratories. This study developed a Web survey that investigated the knowledge, behavior, and attitudes of laboratory staff in order to (1) identify strengths, weaknesses, and gaps of current prion infection prevention and control guidelines and (2) inform the development of national medical lab specific guidelines. The use of qualitative methods to develop a relevant survey is described and future research activities are outlined. Preliminary, qualitative data indicate that, among laboratory staff, there is a high degree of perceived susceptibility toward prion transmission in medical laboratories. Significant barriers to following existing prion infection control guidelines are reported with few benefits of following these guidelines. As a result, laboratories take precautions above those that are required when processing suspect prion-infected specimens, which may result in testing delays. A focused survey for laboratory staff that addresses these issues will provide insight on the necessary steps that will ensure safe and efficient diagnostic testing for suspect prion specimens.