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Published on: January 8, 2015
Neuropathologically distinct prion strains give rise to similar temporal profiles of behavioral deficits
C Cunningham1, R M J Deacon, K Chan
1CNS Inflammation Group, Southampton Neurosciences Group, School of Biological Sciences, Bassett Crescent East, Southampton, SO16 7PX, UK. cc7@soton.ac.uk
Abstract:
Mouse-adapted scrapie strains have been characterized by vacuolation profiles and incubation times, but the behavioral consequences have not been well studied. Here, we compared behavioral impairments produced by ME7, 79A, 22L, and 22A strains in C57BL/6J mice. We show that early impairments on burrowing, glucose consumption, nesting and open field activity, and late stage motor impairments show a very similar temporal sequence in ME7, 79A, and 22L. The long incubation time of the 22A strain produces much later impairments. However, the strains show clear late stage neuropathological differences. All strains showed clear microglial activation and synaptic loss in the hippocampus, but only ME7 and 79A showed significant CA1 neuronal death. Conversely, 22L and 22A showed significant cerebellar Purkinje neuron loss. All strains showed marked thalamic neuronal loss. These behavioral similarities coupled with clear pathological differences could serve to identify key circuits whose early dysfunction underlies the neurological effects of different prion strains.
Insights
Different mouse-adapted scrapie strains (ME7, 79A, 22L, 22A) cause similar early behavioral changes in mice, despite distinct late-stage brain pathology. This finding aids in understanding prion strain-specific neurological effects.
Area of Science:
- Neuroscience
- Prion Disease Research
- Animal Models
Background:
- Mouse-adapted scrapie strains are characterized by vacuolation and incubation times.
- Behavioral consequences of different scrapie strains remain understudied.
- Understanding strain-specific neurodegeneration is crucial for prion disease research.
Purpose of the Study:
- To compare the behavioral impairments caused by ME7, 79A, 22L, and 22A scrapie strains in C57BL/6J mice.
- To correlate behavioral deficits with neuropathological differences across strains.
- To identify key neural circuits affected by prion strain variations.
Main Methods:
- Administration of four distinct mouse-adapted scrapie strains (ME7, 79A, 22L, 22A) to C57BL/6J mice.
- Assessment of early behavioral impairments including burrowing, glucose consumption, nesting, and open field activity.
- Evaluation of late-stage motor deficits and neuropathological changes (neuronal death, microglial activation, synaptic loss) in specific brain regions.
Main Results:
- ME7, 79A, and 22L strains exhibited a similar temporal sequence of early behavioral impairments and late-stage motor deficits.
- The 22A strain showed delayed impairments due to its longer incubation time.
- Neuropathological differences included CA1 neuronal death (ME7, 79A), Purkinje neuron loss (22L, 22A), and thalamic neuronal loss (all strains).
Conclusions:
- Despite distinct neuropathological profiles, several mouse-adapted scrapie strains induce similar early behavioral changes.
- These findings suggest that early behavioral similarities may mask underlying strain-specific neurodegenerative pathways.
- Identifying conserved early circuit dysfunction is key to understanding the diverse neurological effects of prion strains.
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