title: Ultramicroscopy reveals axonal transport impairments in cortical motor neurons at prion disease.
abstract: The functional imaging of neuronal circuits of the central nervous system is crucial for phenotype screenings or investigations of defects in neurodegenerative disorders. Current techniques yield either low penetration depth, yield poor resolution, or are restricted by the age of the animals. Here, we present a novel ultramicroscopy protocol for fluorescence imaging and three-dimensional reconstruction in the central nervous system of adult mice. In combination with tracing as a functional assay for axonal transport, retrogradely labeled descending motor neurons were visualized with >4 mm penetration depth. The analysis of the motor cortex shortly before the onset of clinical prion disease revealed that >80% neurons have functional impairments in axonal transport. Our study provides evidence that prion disease is associated with severe axonal transport defects in the cortical motor neurons and suggests a novel mechanism for prion-mediated neurodegeneration.
authors.affiliation: Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ermolayev
authors.forename: Mike
authors.initials: M
authors.lastname: Friedrich
authors.forename: Revaz
authors.initials: R
authors.lastname: Nozadze
authors.forename: Toni
authors.initials: T
authors.lastname: Cathomen
authors.forename: Michael A
authors.initials: MA
authors.lastname: Klein
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Harms
authors.forename: Eckhard
authors.initials: E
authors.lastname: Flechsig
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000502:physiology / Q000648:ultrastructure*; D004268:DNA-Binding Proteins; D021621:Imaging, Three-Dimensional / Q000379:methods; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D036641:Microscopy, Fluorescence, Multiphoton; D009044:Motor Cortex / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D009046:Motor Neurons / Q000502:physiology* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D016612:Paraffin Embedding; D017096:Prion Diseases / Q000473:pathology / Q000503:physiopathology*
chemical_list: D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins