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Intrahippocampal injection of the murine modified scrapie (ME7) induces a model of prion disease in vivo. Animals inoculated with ME7 brain homogenate were compared to controls at 8, 12 and 21 weeks. The data show that the accumulation of misfolded prion (PrP(Sc)) coincided with selective reduction in presynaptic protein expression early in disease. This(More)
Dendritic structure critically determines the electrical properties of neurons and, thereby, defines the fundamental process of input-to-output conversion. The diversity of dendritic architectures enables neurons to fulfill their specialized circuit functions during cognitive processes. It is known that this dendritic integrity is impaired in patients with(More)
We previously detailed how intrahippocampal inoculation of C57BL/6J mice with murine modified scrapie (ME7) leads to chronic neurodegeneration (Cunningham C, Deacon R, Wells H, Boche D, Waters S, Diniz CP, Scott H, Rawlins JN, Perry VH (2003) Eur J Neurosci 17:2147-2155.). Our characterization of the ME7-model is based on inoculation of this murine modified(More)
A growing body of evidence suggests that the loss of synapses is an early and major component of a number of neurodegenerative diseases. Murine prion disease offers a tractable preparation in which to study synaptic loss in a chronic neurodegenerative disease and to explore the underlying mechanisms. We have previously shown that synaptic loss in the(More)
Synaptic and dendritic pathology is a well-documented component of prion disease. In common with other neurodegenerative diseases that contain an element of protein misfolding, little is known about the underlying mechanisms of synaptic degeneration. In particular, in prion disease the relationship between synaptic malfunction, degeneration, and(More)
Synaptic abnormalities, one of the key features of prion disease pathogenesis, gives rise to functional deficits and contributes to the devastating clinical outcome. The synaptic compartment is the first to succumb in several neurodegenerative diseases linked with protein misfolding but the mechanisms underpinning this are poorly defined. In our current(More)
Prion diseases are characteristically accompanied by extensive synaptic pathology that can occur during the preclinical phase of the disease and, in animal models, correlates with the first decline of hippocampus-dependent cognitive functions. This pathology is defined by abnormally shaped synapses in which the postsynaptic membrane modifies its curvature(More)
In chronic neurodegenerative diseases associated with aggregates of misfolded proteins (such as Alzheimer's, Parkinson's and prion disease), there is an early degeneration of presynaptic terminals prior to the loss of the neuronal somata. Identifying the mechanisms that govern synapse degeneration is of paramount importance, as cognitive decline is strongly(More)
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