title: 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.
authors.affiliation: Division of Neuroanatomy and Behaviour, Institute of Anatomy and Centre for Neuroscience, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. dellomo@iss.it
authors.forename: Giacomo
authors.initials: G
authors.lastname: Dell'Omo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Vannoni
authors.forename: Alexei L
authors.initials: AL
authors.lastname: Vyssotski
authors.forename: Michele Angelo
authors.initials: MA
authors.lastname: Di Bari
authors.forename: Romolo
authors.initials: R
authors.lastname: Nonno
authors.forename: Umberto
authors.initials: U
authors.lastname: Agrimi
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Lipp
mesh_terms: D000818:Animals; D002417:Cattle; D002940:Circadian Rhythm / Q000502:physiology*; D016643:Encephalopathy, Bovine Spongiform / Q000145:classification / Q000175:diagnosis* / Q000503:physiopathology / Q000523:psychology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008991:Monitoring, Physiologic / Q000379:methods*; D009043:Motor Activity / Q000502:physiology*; D017096:Prion Diseases / Q000145:classification / Q000503:physiopathology / Q000523:psychology; D012608:Scrapie / Q000145:classification / Q000175:diagnosis* / Q000503:physiopathology / Q000523:psychology