NR AXBK
AU Fuhrmann,M.; Mitteregger,G.; Kretzschmar,H.A.; Herms,J.
TI Dendritic pathology in prion disease starts at the synaptic spine
QU Journal of Neuroscience 2007 Jun 6; 27(23): 6224-33
PT comparative study; journal article; research support, non-u.s. gov't
AB Spine loss represents a common hallmark of neurodegenerative diseases. However, little is known about the underlying mechanisms, especially the relationship between spine elimination and neuritic destruction. We imaged cortical dendrites throughout a neurodegenerative disease using scrapie in mice as a model. Two-photon in vivo imaging over 2 months revealed a linear decrease of spine density. Interestingly, only persistent spines (lifetime > or = 8 d) disappeared, whereas the density of transient spines (lifetime < or = 4 d) was unaffected. Before spine loss, dendritic varicosities emerged preferentially at sites where spines protrude from the dendrite. These results implicate that the location where the spine protrudes from the dendrite may be particularly vulnerable and that dendritic varicosities may actually cause spine loss.
MH Animals; Dendrites/pathology/ultrastructure; Dendritic Spines/*pathology/ultrastructure; Mice; Mice, Inbred C57BL; Mice, Transgenic; Prion Diseases/*pathology; Somatosensory Cortex/pathology/ultrastructure; Synapses/*pathology/ultrastructure
AD Center of Neuropathology and Prion Research, Ludwig Maximilians University, 81377 Munich, Germany.
SP englisch
PO USA