NR ATPN
AU Fuhrmann,M.; Wuensch,G.; Kretzschmar,H.A.; Herms,J.W.
TI In vivo Two-Photon-Analysis of Spine Pathology in Prion Disease
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Pathogenesis PATH-24
AD Martin Fuhrmann, Gerda Wuensch, Hans Kretzschmar, Jochen Herms, Ludwig Maximilians University, Germany
PT Konferenz-Poster
AB
Neuronal death is a prominent, but poorly understood, pathological hallmark of prion disease. Although neuronal death appears to be mediated by apoptosis, the triggering mechanisms remain unknown. A few histological and ultrastructural studies indicate that early synaptic pathology may be an early event causing a disruption of neuronal circuitry and initiation of apoptotic neuronal cell death. Here we aim to analyze early synaptic pathology in prion disease in detail performing in vivo two-photon imaging in scrapie infected mice. Infected transgenic mice included in this study express YFP in different neuronal subsets thus facilitating the resolution and intravital imaging of apical dendritic spines over extended time periods. Especially we studied the kinetics of spine degeneration in apical dendrites of YFP positive layer 5 pyramidal neurons within the somatosensory cortex following RML i.c. infection. We observe stable dendritic spine turnover at 130 d.p.i. over a time period of 3 hours. Additionally dendritic spine density per volume was analyzed from in vivo imaging experiments. Dendritic spine density is significantly reduced at 130 d.p.i. in comparison to 100 d.p.i. whereas the number of neurons is unchanged at this time point of disease. Morphological analysis revealed dendritic swellings and brakeage, however sprouting or spine hypertrophy was not detectable. Thus already at early stages of Prion infection from 100 to 130 d.p.i. significant structural changes take place at the synapse.
Our results strongly indicate that synaptic degeneration is an early phenomenon during prion disease incubation preceding neurodegeneration. Obviously spine degeneration in prion disease is a slowly progressing phenomenon without any signs of regeneration or compensation like sprouting or spine hypertrophy in Alzheimer's disease. This indicates a primarily toxic event at the spine causing neurodegeneration in prion disease.
SP englisch
PO Deutschland