Early behavioural changes in mice infected with BSE and scrapie: automated home cage monitoring reveals prion strain differences

Abstract

Mice inoculated with transmissible spongiform encephalopathies (TSE) show behavioural abnormalities well before the appearance of clinical signs. TSE strains are obtained by serial re-infection of infectious brain homogenates in laboratory rodents. They are characterized by strain-typical brain lesion profiles, which implies that they might be differentiated behaviourally as well. Seventy female C57BL/6 mice were tested, 14 per group. Controls received no or sham inocula, two other groups received scrapie strains adapted to mice (139A, ME7) and one group a mouse-adapted BSE strain (301C). From week 7 until the end of the incubation period, 8 mice per group were subjected once every 2 weeks to open-field and hot-plate tests. Assessment of clinical signs, and measuring of body weight, food and water consumption were carried out weekly on the remaining animals kept in single cages. In addition, locomotor activity was recorded continuously in these mice by means of infrared detectors. Monitoring of circadian activity revealed early significant TSE strain differences, most pronounced during the nocturnal active phase. Behavioural changes in open-field tests also occurred before the appearance of clinical signs, and differences in rearing, wall rearing and sniffing were strain-specific, however, such differences varied according to the period of testing. Hind paw lick latencies increased equally in all groups after week 19, jump latencies also increased in the two scrapie groups but not in the BSE group. It was at this time that clinical signs first appeared consisting of ataxia, lack of balance, motor dyscoordination, and lordosis. These data imply that automated assessment of circadian activity in mice is a powerful and economical tool for early behavioural typing of TSE strains.

Neurobehavioral Testing in Prion Disease Studies

“…Scrapie inoculated mice did show a decline in water consumption around 10 weeks post inoculation, consistent with data published by Outram [81]. All mice exhibited similar scrapie induced neuropathological changes [83]. Taken together, these studies indicate that scrapie strain and mouse strain may impact the outcome of behavioral assays.…”

“…In contrast, ME7 inoculated mice also showed a decline in activity during the dark phase, although not to the same extent as 301C inoculated mice. Statistically significant scrapie strain effects were observed in measures of the duration of several open field behaviors including, rearing, wall rearing, sniffing, grooming, and walking [83]. Scrapie inoculated mice did show a decline in water consumption around 10 weeks post inoculation, consistent with data published by Outram [81].…”

“…Although there was no effect of scrapie strain on y-maze spontaneous alternation, 79-A inoculated mice exhibited an increased number of arm entries. The strain specificity of prion clinical phenotype was further demonstrated by a study examining behavioral effects on C57BL/6 mice IC inoculated with either the scrapie strains 139A or ME7 or the mouse adapted BSE strain 301C [83]. Mice inoculated with 301C were generally less active during the dark phase of the light-dark cycle than control or scrapie inoculated mice.…”

The power of automated high-resolution behavior analysis revealed by its application to mouse models of Huntington's and prion diseases

“…Prioninfected mice exhibit hunched posture, ataxia, tail rigidity, priapism, and death (12). Behavioral abnormalities such as disturbances in food intake and activity vary depending on the mouse strain as well as the prion strain (13,14). The diversity of PrD symptoms provides excellent candidates for higherresolution behavioral analysis.…”

Striatal pathology underlies prion infection-mediated hyperactivity in mice

“…26,[38][39][40][41] Given that "Chandler" strain of scrapie. 31 Dell'Omo et al 32 conducted a similar comparative prion strain study, using laser-beam breaks to determine activity levels caused by of several different prion stains inoculated into C57BL/6 female mice. In their study 139A caused a hyperactivity phenotype in the home cage but of considerably smaller amplitude than what we observed whereas the other two strains that they tested, 301C and ME7, both caused rather dramatic hypoactivity (3-fold reduction in activity counts).…”