Behavioral consequences of prion disease targeted to the hippocampus in a mouse model of scrapie

Betmouni, Samar, Deacon, Robert M.J., Rawlins, J. Nicholas P. and Perry, V. Hugh (1999) Behavioral consequences of prion disease targeted to the hippocampus in a mouse model of scrapie. Psychobiology, 27 (1), 63-71. (doi:10.3758/BF03332100).

Abstract

Sheep scrapie is an archetypal member of a group of chronic neurodegenerative diseases that can afflict both humans and animals and that are known collectively as the transmissible spongiform encephalopathies or prion diseases. The study of these diseases has been facilitated by the experimental transmission of sheep scrapie to laboratory rodents, and this has led to an ever-increasing literature on the pathogenesis and molecular biology of this unusual group of diseases. There is relatively little known about the relationship between the chronic neurodegenerative process and the development of clinical signs, the latter occurring very late in the course of the disease after a prolonged incubation period. We have previously shown that following intrahippocampal injection of scrapie brain homogenate, there is an early inflammatory response in the brains of affected mice. This develops long before there is neuronal loss and also before the mice develop any overt clinical signs of disease. It was surprising that despite the marked and evolving inflammatory response in the brains of scrapie-affected mice, indicative of underlying pathology, there were no outward signs that the mice had any form of central nervous system pathology. The present study shows that by using a number of behavioral tasks, including multitrial passive avoidance, open-field motor activity, and tests of muscle strength, it is possible to detect more subtle clinical signs much earlier during the course of disease in scrapie-affected mice. The relevance of this finding to the investigation of mouse scrapie is discussed.

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