At the centre of neuronal, synaptic and axonal pathology in murine prion disease: degeneration of neuroanatomically linked thalamic and brainstem nuclei

摘要: Aims The processes by which neurons degenerate in chronic neurodegenerative diseases remain unclear. Synaptic loss and axonal pathology frequently precede neuronal protein aggregation demonstrably spreads along neuroanatomical pathways many diseases. The spread of is less studied. Methods We previously demonstrated severe neurodegeneration the posterior thalamus multiple prion disease strains. Here we used ME7 model to examine nature this degeneration major brainstem projections into region. Results We objectively quantified neurological decline between 16 18 weeks post-inoculation observed thalamic subregion-selective neuronal, synaptic while demonstrating relatively uniform protease-resistant (PrP) microgliosis across thalamus. Novel amyloid precursor (APP) was particularly prominent (PO) ventroposterior lateral (VPL) nuclei. nuclei forming these were examined. Massive PO not matched significant interpolaris (Sp5I), massive ventral posteromedial nucleus (VPM) did correspond with principal trigeminal nucleus. Likewise, VPL gracile cuneate nuclei. Conclusion These findings demonstrate from disease. divergent neuropathological features adjacent populations demonstrates that there are discrete different populations.