NR AXUJ
AU Perry,H.; Cunningham,C.; Lunnon,K.; Gray,B.; O'Connor,V.
TI Neuropathogenesis and Neuroinflammation in ME7 Murine Prion Disease: Implications for Alzheimer's Disease
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.187
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB The neuropathology of prion disease is characterised by tissue vacuolation, loss of neurons, the presence of PrPsc, reactive astrocytes and activated microglia. The molecular events that lead to loss of neurons and the contribution of inflammatory processes to disease progression are poorly understood. We have sought to discover the neuropathological changes that underpin the earliest behavioural changes in the ME7 model of mouse prion disease and to characterise the associated inflammatory response. The earliest neuropathological changes associated with behavioural abnormalities are in the hippocampus where there is a loss of synapses from CA3 Schaeffer collaterals onto pyramidal cells of CA1. Biochemical analysis shows that components of the pre-synaptic vesicles are the first to show reduced expression. In response to this large-scale synaptic degeneration the microglia adopt an activated morphology and increase in number. However, despite their activated morphology their phenotype is dominated by receptors expressing immunomodulatory tyrosine inhibitory motifs (ITIMs) characteristic of an anti-inflammatory phenotype and the cytokine profile is also anti-inflammatory and dominated by the cytokine TGFb1. In contrast, a systemic inflammatory challenge (LPS) in animals with prion disease switches the microglia to a proinflammatory response and leads to upregulated expression of receptors with activating motifs (ITAMs). Previous studies have shown that systemic challenge with LPS in animals with prion disease leads to an increase in the number of neurons undergoing apoptosis (Cunningham et al 2005). These data serve to focus attention on the possible role of systemic inflammation in prion disease and other neurodegenerative diseases.
AD H. Perry, K. Lunnon, B. Gray, V. O'Connor, University of Southampton, School of Biological Sciences, UK; C. Cunningham, Trinity College, Ireland
SP englisch
PO Schottland