Gunapala, Keith M. and Chang, Daniel and Hsu, Cynthia T. and Manaye, Kebreten and Drenan, Ryan M. and Switzer, Robert C. and Steele, Andrew D. (2010) Striatal pathology underlies prion infection-mediated hyperactivity in mice. Prion, 4 (4). pp. 302-315. ISSN 1933-6896 http://resolver.caltech.edu/CaltechAUTHORS:20110207-100925893
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Although prion diseases are most commonly modeled using the laboratory mouse, the diversity of prion strains, behavioral testing and neuropathological assessments hamper our collective understanding of mouse models of prion disease. Here we compared several commonly used murine strains of prions in C57BL/6J female mice in a detailed home cage behavior detection system and a systematic study of pathological markers and neurotransmitter systems. We observed that mice inoculated with RML or 139A prions develop a severe hyperactivity phenotype in the home cage. A detailed assessment of pathology markers, such as microglial marker IBA1, astroglial marker GFAP and degeneration staining indicate early striatal pathology in mice inoculated with RML or 139A but not in those inoculated with 22L prions. An assessment of neuromodulatory systems including serotonin, dopamine, noradrenalin and acetylcholine showed surprisingly little decline in neuronal cell bodies or their innervations of regions controlling locomotor behavior, except for a small decrease in dopaminergic innervations of the dorsal striatum. These results implicate the dorsal striatum in mediating the major behavioral phenotype of 139A and RML prions. Further, they suggest that measurements of activity may be a sensitive manner in which to diagnose murine prion disease. With respect to neuropathology, our results indicate that pathological stains as opposed to neurotransmitter markers are much more informative and sensitive as markers of prion disease in mouse models.
|Additional Information:||© 2010 Landes Bioscience. Submitted: 09/02/10; Accepted: 09/22/10. We thank Susan Lindquist for providing the 22L and RML prion strains, Claudio Hetz for providing 139A prions and Henry Lester for helpful advice. This work was funded by the Broad Fellows in Brain Circuitry Program at Caltech.|
|Subject Keywords:||PrP; neurodegeneration; protein misfolding; home-cage; transmissible spongiform encephalopathy|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||10 Mar 2011 20:40|
|Last Modified:||10 Mar 2011 20:40|
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