TY  - JOUR
AU  - Ulusoy, Ayse
AU  - Musgrove, Ruth E
AU  - Rusconi, Raffaella
AU  - Klinkenberg, Michael
AU  - Helwig, Michael
AU  - Schneider, Anja
AU  - Di Monte, Donato A
TI  - Neuron-to-neuron α-synuclein propagation in vivo is independent of neuronal injury.
JO  - Acta Neuropathologica Communications
VL  - 3
IS  - 1
SN  - 2051-5960
CY  - London
PB  - Biomed Central
M1  - DZNE-2020-04403
SP  - 13
PY  - 2015
AB  - 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.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.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.
KW  - Animals
KW  - Brain: metabolism
KW  - Disease Models, Animal
KW  - Female
KW  - Gene Transfer Techniques
KW  - Humans
KW  - Medulla Oblongata: metabolism
KW  - Nerve Degeneration: metabolism
KW  - Nerve Degeneration: pathology
KW  - Neural Pathways: metabolism
KW  - Neural Pathways: pathology
KW  - Neurons: metabolism
KW  - Neurons: pathology
KW  - Parkinson Disease: metabolism
KW  - Rats
KW  - Rats, Sprague-Dawley
KW  - alpha-Synuclein: metabolism
KW  - SNCA protein, human (NLM Chemicals)
KW  - alpha-Synuclein (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25853980
C2  - pmc:PMC4369863
DO  - DOI:10.1186/s40478-015-0198-y
UR  - https://pub.dzne.de/record/138081
ER  -