Early behavioural changes in scrapie-affected mice and the influence of dapsone

Behavioural testing can reveal effects in scrapie-infected mice long before overt clinical signs appear (Betmouni et al., 1999, Psychobiology, 27, 63-71). These effects may be partly attributable to an early, atypical inflammatory response in the brain (Betmouni et al., 1996, Neuroscience, 74, 1-5). The present study replicated and extended these findings, and examined the effect of chronic treatment with dapsone. This anti-inflammatory compound has been reported to delay disease onset in a rat model of Creutzfeldt-Jakob disease (Manuelidis et al., 1998, Lancet, 352, 456). Although the doses used in the present study were higher than those of Manuelidis et al. (1998), no attenuation of the disease was seen in either behavioural or subsequent histological tests. Burrowing, i.e. displacing food pellets from a tube in the home cage, decreased from around week 12 in scrapie-infected mice, as did consumption of palatable glucose solution. Concurrently, ambulation in an open field increased, as did rearing at around week 17. Spontaneous alternation was impaired around this time. Around 18 weeks, motor performance on an inverted screen, horizontal bar, rotating rod and static rods decreased. Nest construction was impaired at 20 weeks. Overt clinical signs (reduction in mobility, hunched posture, poor coat condition, bladder enlargement) only occurred after week 20, when the mice were prepared for histology. The ME7 scrapie-infected mice thus showed a characteristic complex of neurological and behavioural changes during the course of the disease that were not ameliorated by dapsone. These changes appeared well before clinical signs were prominent.