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- Title
Trans-synaptic spreading of alpha-synuclein pathology through sensory afferents leads to sensory nerve degeneration and neuropathic pain.
- Authors
Ferreira, Nelson; Gonçalves, Nádia Pereira; Jan, Asad; Jensen, Nanna Møller; van der Laan, Amelia; Mohseni, Simin; Vægter, Christian Bjerggaard; Jensen, Poul Henning
- Abstract
Pain is a common non-motor symptom of Parkinson's disease (PD), with current limited knowledge of its pathophysiology. Here, we show that peripheral inoculation of mouse alpha-synuclein (α-Syn) pre-formed fibrils, in a transgenic mouse model of PD, elicited retrograde trans-synaptic spreading of α-Syn pathology (pSer129) across sensory neurons and dorsal nerve roots, reaching central pain processing regions, including the spinal dorsal horn and the projections of the anterolateral system in the central nervous system (CNS). Pathological peripheral to CNS propagation of α-Syn aggregates along interconnected neuronal populations within sensory afferents, was concomitant with impaired nociceptive response, reflected by mechanical allodynia, reduced nerve conduction velocities (sensory and motor) and degeneration of small- and medium-sized myelinated fibers. Our findings show a link between the transneuronal propagation of α-Syn pathology with sensory neuron dysfunction and neuropathic impairment, suggesting promising avenues of investigation into the mechanisms underlying pain in PD.
- Subjects
NEURODEGENERATION; AFFERENT pathways; ALPHA-synuclein; CENTRAL nervous system; PARKINSON'S disease; CENTRAL nervous system physiology; SPREADING cortical depression; BRAIN stimulation
- Publication
Acta Neuropathologica Communications, 2021, Vol 9, Issue 1, p1
- ISSN
2051-5960
- Publication type
Article
- DOI
10.1186/s40478-021-01131-8