title: Neuron-to-neuron α-synuclein propagation in vivo is independent of neuronal injury.
abstract: BACKGROUND
  Interneuronal propagation of α-synuclein has been demonstrated in a variety of experimental models and may be involved in disease progression during the course of human synucleinopathies. The aim of this study was to assess the role that neuronal injury or, vice versa, cell integrity could have in facilitating interneuronal α-synuclein transfer and consequent protein spreading in an in vivo animal model.
  
  
  RESULTS
  Viral vectors carrying the DNA for human α-synuclein were injected into the rat vagus nerve to trigger protein overexpression in the medulla oblongata and consequent spreading of human α-synuclein toward pons, midbrain and forebrain. Two vector preparations sharing the same viral construct were manufactured using identical procedures with the exception of methods for their purification. They were also injected at concentrations that induced comparable levels of α-synuclein transduction/overexpression in the medulla oblongata. α-Synuclein load was associated with damage (at 6 weeks post injection) and death (at 12 weeks) of medullary neurons after treatment with only one of the two vector preparations. Of note, neuronal injury and degeneration was accompanied by a substantial reduction of caudo-rostral propagation of human α-synuclein.
  
  
  CONCLUSIONS
  Interneuronal α-synuclein transfer, which underlies protein spreading from the medulla oblongata to more rostral brain regions in this rat model, is not a mere consequence of passive release from damaged or dead neurons. Neuronal injury and degeneration did not exacerbate α-synuclein propagation. In fact, data suggest that cell-to-cell passage of α-synuclein may be particularly efficient between intact, relatively healthy neurons.
authors: Ayse
authors: A
authors: Ulusoy
authors: Ruth E
authors: RE
authors: Musgrove
authors: Raffaella
authors: R
authors: Rusconi
authors: Michael
authors: M
authors: Klinkenberg
authors: Michael
authors: M
authors: Helwig
authors: Anja
authors: A
authors: Schneider
authors: Donato A
authors: DA
authors: Di Monte
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D008526:Medulla Oblongata / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D009434:Neural Pathways / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010300:Parkinson Disease / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein