Olfactory behavior as an indicator of prion infection

Abstract

The current project sought to identify changes in olfactory-related behavior in hamsters infected with the HY transmissible mink encephalopathy (HY TME) strain of the pathological form of the prion protein. Experiment 1 was conducted to validate an olfactory preference paradigm for use with Syrian golden hamsters. An experimental group was induced with anosmia by treating them with methimazole. In an olfactory preference test in which the time subjects spent investigating attractive, aversive, and neutral olfactory stimuli were assessed, control animals spent a significantly longer amount of time investigating the attractive versus aversive scents. The methimazole-treated group did not demonstrate this pattern. Experiment 2 investigated changes in olfactory behavior as a result of prion infection. A group of hamsters was infected with HY TME and subjected to olfactory preference testing at four time points: 20, 40, 60, and 80 days post inoculation. In addition, parallel subjects were sacrificed and submitted to immunohistochemical analysis in order to examine the proliferation of HY TME throughout olfactory-related brain structures with the intention of relating behavioral changes to the progression of prion infection. Results indicated that HY TME subjects lost their ability to perceive the attractive scent early in the disease. However, avoidance of the aversive scent was retained until much later. The immunohistochemistry revealed an initial appearance of the pathologic prion at 20 days post inoculation in the glomeruli of the olfactory bulb. Widespread infection throughout all olfactory structures was observed at 40 days post inoculation and beyond. These results suggested a differential sensory loss to the olfactory stimuli that may have been due to initial infection in the glomeruli and later infection in other olfactory structures. These findings support the utility of discrimination paradigms for the diagnosis of prion diseases.