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

@article{citeulike:3251932, abstract = {Prion diseases are fatal, chronic neurodegenerative diseases of mammals, characterized by amyloid 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.}, address = {CNS Inflammation Group, Southampton Neuroscience Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK. C.Cunningham@soton.ac.uk}, author = {Cunningham, C. and Deacon, R. and Wells, H. and Boche, D. and Waters, S. and Diniz, C. P. and Scott, H. and Rawlins, J. N. and Perry, V. H.}, citeulike-article-id = {3251932}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/12786981}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=12786981}, issn = {0953-816X}, journal = {The European journal of neuroscience}, keywords = {compartmental, disease, prion, synapse}, month = {May}, number = {10}, pages = {2147--2155}, posted-at = {2008-09-13 15:35:50}, priority = {4}, title = {Synaptic changes characterize early behavioural signs in the ME7 model of murine prion disease.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/12786981}, volume = {17}, year = {2003} }

TY - JOUR ID - citeulike:3251932 L3 - citeulike-article-id:3251932 N2 - Prion diseases are fatal, chronic neurodegenerative diseases of mammals, characterized by amyloid 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. IS - 10 JF - The European journal of neuroscience SN - 0953-816X AD - CNS Inflammation Group, Southampton Neuroscience Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK. C.Cunningham@soton.ac.uk EP - 2155 TI - Synaptic changes characterize early behavioural signs in the ME7 model of murine prion disease. VL - 17 SP - 2147 KW - compartmental KW - disease KW - prion KW - synapse AU - Cunningham, C AU - Deacon, R AU - Wells, H AU - Boche, D AU - Waters, S AU - Diniz, CP AU - Scott, H AU - Rawlins, JN AU - Perry, VH PY - 2003/05// UR - http://view.ncbi.nlm.nih.gov/pubmed/12786981 ER -