title: Dendritic pathology in prion disease starts at the synaptic spine.
abstract: 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.
authors.affiliation: Center of Neuropathology and Prion Research, Ludwig Maximilians University, 81377 Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Fuhrmann
authors.forename: Gerda
authors.initials: G
authors.lastname: Mitteregger
authors.forename: Hans
authors.initials: H
authors.lastname: Kretzschmar
authors.forename: Jochen
authors.initials: J
authors.lastname: Herms
mesh_terms: D000818:Animals; D003712:Dendrites / Q000473:pathology / Q000648:ultrastructure; D049229:Dendritic Spines / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000473:pathology*; D013003:Somatosensory Cortex / Q000473:pathology / Q000648:ultrastructure; D013569:Synapses / Q000473:pathology* / Q000648:ultrastructure