Synaptic changes characterize early behavioural signs in the ME7 model of murine prion disease


Cunningham, C., Deacon, R., Wells, H., Boche, D., Waters, E., Picanco Diniz, C., Scott, H., Rawlins, JNP. and Perry, VH. (2003) Synaptic changes characterize early behavioural signs in the ME7 model of murine prion disease. European Journal of Neuroscience, 17, (10), 2147-2155. (doi:10.1046/j.1460-9568.2003.02662.x).

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Description/Abstract

Prion diseases are fatal, chronic neurodegenerative diseases of mammals, characterized byamyloid deposition, astrogliosis, microglial
activation, tissue vacuolation and neuronal loss. In the ME7 model of prion disease in the C57BL/6 J mouse, we have shown previously
that these animals display behavioural changes that indicate the onset of neuronal dysfunction. The current study examines the
neuropathological correlates of these early behavioural changes. After injection of ME7-infected homogenate into the dorsal
hippocampus, we found statistically significant impairment of burrowing, nesting and glucose consumption, and increased open field
activity at 13 weeks. At this time, microglia activation and PrPSc deposition was visible selectively throughout the limbic system,
including the hippocampus, entorhinal cortex, medial and lateral septum, mamillary bodies, dorsal thalamus and, to a lesser degree, in
regions of the brainstem. No increase in apoptosis or neuronal cell loss was detectable at this time, while in animals at 19 weeks
postinjection there was 40% neuronal loss from CA1. There was a statistically significant reduction in synaptophysin staining in the
stratum radiatum of the CA1 at 13 weeks indicating loss of presynaptic terminals. Damage to the dorsal hippocampus is known to
disrupt burrowing and nesting behaviour. We have demonstrated a neuropathological correlate of an early behavioural deficit in prion
disease and suggest that this should allow insights into the first steps of the neuropathogenesis of prion diseases.

Item Type: Article
ISSNs: 0953-816X (print)
Related URLs:
Keywords: hippocampus, neurodegeneration, neuronal dysfunction, scrapie, synapse
Subjects: R Medicine > RB Pathology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Q Science > QH Natural history > QH301 Biology
Divisions: University Structure - Pre August 2011 > School of Medicine > Clinical Neurosciences
University Structure - Pre August 2011 > School of Biological Sciences
ePrint ID: 23975
Date Deposited: 17 Mar 2006
Last Modified: 27 Mar 2014 18:13
URI: http://eprints.soton.ac.uk/id/eprint/23975

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