Change in tau phosphorylation associated with neurodegeneration in the ME7 model of prion disease
Asuni, Ayodeji A., Perry, V. Hugh and O'Connor, Vincent (2010) Change in tau phosphorylation associated with neurodegeneration in the ME7 model of prion disease. Biochemical Society Transactions, 38, (2), 545-551. (doi:10.1042/BST0380545). (PMID:20298219).
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Hyperphosphorylation of the microtubule-associated protein tau is a significant determinant in AD (Alzheimer's disease), where it is associated with disrupted axonal transport and probably causes synaptic dysfunction. Although less well studied, hyperphosphorylation has been observed in prion disease. We have investigated the expression of hyperphosphorylated tau in the hippocampus of mice infected with the ME7 prion agent. In ME7-infected animals, there is a selective loss of CA1 synapse, first discernable at 13 weeks of disease. There is a potential that dysfunctional axonal transport contributes to this synaptopathy. Thus investigating hyperphosphorylated tau that is dysfunctional in AD could illuminate whether and how they are significant in prion disease. We observed no differences in the levels of phosphorylated tau (using MC1, PHF-1 and CP13 antibodies) in detergent-soluble and detergent-insoluble fractions extracted from ME7- and NBH- (normal brain homogenate) treated animals across disease. In contrast, we observed an increase in phospho-tau staining for several epitopes using immunohistochemistry in ME7-infected hippocampal sections. Although the changes were not of the magnitude seen in AD tissue, clear differences for several phospho-tau species were seen in the CA1 and CA3 of ME7-treated animals (pSer(199-202)>pSer(214)>PHF-1 antibody). Temporally, these changes were restricted to animals at 20 weeks and none of the disease-related staining was associated with the axons or dendrites that hold CA1 synapses. These findings suggest that phosphorylation of tau at the epitopes examined does not underpin the early synaptic dysfunction. These data suggest that the changes in tau phosphorylation recorded here and observed by others relate to end-stage prion pathology when early dysfunctions have progressed to overt neuronal loss.
|Digital Object Identifier (DOI):||doi:10.1042/BST0380545|
|Subjects:||R Medicine > R Medicine (General)|
|Divisions:||University Structure - Pre August 2011 > School of Biological Sciences
|Date Deposited:||06 Apr 2011 10:44|
|Last Modified:||27 Mar 2014 19:34|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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