The title of the post is a copy and paste from the subtitle and first paragraph of the linked academic press release here:

> Parkinson's may start in the gut and travel up to the brain via the vagus nerve.

> Experiments in mice at Johns Hopkins Medicine suggest that the transmission of a toxic neuron-killing protein (α-syn) associated with Parkinson's disease originates among cells in the gut and travels up to the brain by hijacking the vagus nerve. This paper, "Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson’s Disease," was published today in the journal Neuron.

Journal Reference:

Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson’s Disease

Sangjune Kim 11
Seung-Hwan Kwon 11
Tae-In Kam
Nikhil Panicker
Senthilkumar S. Karuppagounder
Saebom Lee
Jun Hee Lee 9
Wonjoong Richard Kim
Minjee Kook
Catherine A. Foss
Chentian Shen 10
Hojae Lee
Subhash Kulkarni
Pankaj J. Pasricha
Gabsang Lee
Martin G. Pomper
Valina L. Dawson
Ted M. Dawson 12
Han Seok Ko

Neuron

Published: June 26, 2019

Link: https://www.cell.com/neuron/fulltext/S0896-6273(19)30488-X

DOI: https://doi.org/10.1016/j.neuron.2019.05.035
PlumX Metrics

Highlights

• Gut-to-brain propagation of pathologic α-synuclein via the vagus nerve causes PD

• Dopamine neurons degenerate in the pathologic α-synuclein gut-to-brain model of PD

• Gut injection of pathologic α-synuclein causes PD-like motor and non-motor symptoms

• PD-like pathology and symptoms require endogenous α-synuclein

Summary

Analysis of human pathology led Braak to postulate that α-synuclein (α-syn) pathology could spread from the gut to brain via the vagus nerve. Here, we test this postulate by assessing α-synucleinopathy in the brain in a novel gut-to-brain α-syn transmission mouse model, where pathological α-syn preformed fibrils were injected into the duodenal and pyloric muscularis layer. Spread of pathologic α-syn in brain, as assessed by phosphorylation of serine 129 of α-syn, was observed first in the dorsal motor nucleus, then in caudal portions of the hindbrain, including the locus coeruleus, and much later in basolateral amygdala, dorsal raphe nucleus, and the substantia nigra pars compacta. Moreover, loss of dopaminergic neurons and motor and non-motor symptoms were observed in a similar temporal manner. Truncal vagotomy and α-syn deficiency prevented the gut-to-brain spread of α-synucleinopathy and associated neurodegeneration and behavioral deficits. This study supports the Braak hypothesis in the etiology of idiopathic Parkinson’s disease (PD).