NR AUQP
AU Fuhrmann,M.; Mitteregger,G.; Kretzschmar,H.A.; Herms,J.W.
TI In Vivo Two-Photon-Analysis of Spine Pathology in Prion Disease
QU TSE-Forum, 6. Kongress - Nationale TSE-Forschungsplattform, Greifswald 26.6.-28.6.2006, Vortrag V-08
PT Konferenz-Vortrag
AB
Here we aim to analyze the kinetic of synaptic pathology in prion disease by performing in vivo two-photon imaging in scrapie infected mice. Infected transgenic mice included in this study express yellow fluorescent protein (YFP) in different neuronal subsets thus facilitating the resolution and intravital imaging of dendritic spines. Especially we aim to get to know the kinetics of spine degeneration in apical dendrites of YFP positive layer 5 pyramidal neurons within the somatosensory cortex following RML i.c. infection.
The analysis revealed stable spine turnover over time periods of 1.5 to 3 hours at 100, 130 and 145 d.p.i. indicating that the dendritic spine loss is not a phenomenon occurring within hours. Repeated analysis of single apical dendritic spines and dendrites revealed dendritic spine stability until a certain time point of the disease. When symptoms of terminally ill mice are clearly visible rapid spine loss followed by dendritic brakeage and swelling within in days to weeks can be detected. Interestingly shortly before the period of vast spine loss, a phase of dendritic spine gain emerges. This indicates that the postsynapse has the capacity to regenerate, indicating that it is functionally intact at that stage of disease.
Here we demonstrate for the first time the kinetic of synaptic degeneration in a living animal infected with scrapie prions. 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 within days to weeks preceded by a phase of dendritic spine gain. This core finding indicates that spine degeneration in prion disease is not primarily due to a defect of the postsynapse. Rather one can hypothesize that spine loss during scrapie infection is a consequence of a degeneration or dysfunction of the presynapse.
AD Martin Fuhrmann, Gerda Mitteregger, Hans Kretzschmar, Jochen Herms, Center of Neuropathology and Prion research, Ludwig Maximilians University, 81377 Munich, Germany
SP englisch
PO Deutschland
OR Tagungsband