Splanchnic-spinal transmission of gut-initiated α-synucleinopathy
- 1Institute for Basic Science (IBS), Center for Microbiome-Body-Brain Physiology, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea 6
Abstract
Gut-initiated -synucleinopathy is proposed to spread from the gastrointestinal tract to the CNS, contributing to Parkinson's disease (PD), but whether routes beyond the vagus nerve are involved remains unclear. Using complementary intracolonic rotenone and gastroduodenal -synuclein PFF models, we combined pathway-specific surgical interruption with longitudinal behavioral analysis and anatomical mapping of pathological -synuclein. In the intracolonic rotenone model, interruption of the prevertebral ganglia/splanchnic-spinal axis more strongly attenuated behavioral deficits and -synuclein pathology than vagotomy. In the gastroduodenal PFF model, both vagal and splanchnic-spinal pathways contributed to pathology propagation. Early after PFF inoculation, pathological -synuclein was detected in peripheral neural structures associated with both routes. Consistent with these findings, spinal pathology was evident in human PD. Together, these results identify the splanchnic-spinal pathway as a key component of body-first Parkinson's disease, broadening current models of peripheral-to-central disease progression and informing efforts to target early peripheral disease progression.
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BibTeX
@misc{jung2026splanchnicspinal,
title = {{Splanchnic-spinal transmission of gut-initiated α-synucleinopathy}},
author = {B.-K. Jung and M. K. Song and Y. Kim and D. K. Hong and M. You and E. H. Ahn and S. S. Kang and T.-I. Kam and H. Park and Y.-S. Kim and G. S. B. Suh},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.19.760019},
url = {https://www.biorxiv.org/content/10.64898/2026.10.19.760019v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Splanchnic-spinal transmission of gut-initiated α-synucleinopathy
AU - B.-K. Jung
AU - M. K. Song
AU - Y. Kim
AU - D. K. Hong
AU - M. You
AU - E. H. Ahn
AU - S. S. Kang
AU - T.-I. Kam
AU - H. Park
AU - Y.-S. Kim
AU - G. S. B. Suh
PY - 2026
DA - 2026/10/19
PB - bioRxiv
DO - 10.64898/2026.10.19.760019
UR - https://www.biorxiv.org/content/10.64898/2026.10.19.760019v1
AB - Gut-initiated -synucleinopathy is proposed to spread from the gastrointestinal tract to the CNS, contributing to Parkinson's disease (PD), but whether routes beyond the vagus nerve are involved remains unclear. Using complementary intracolonic rotenone and gastroduodenal -synuclein PFF models, we combined pathway-specific surgical interruption with longitudinal behavioral analysis and anatomical mapping of pathological -synuclein. In the intracolonic rotenone model, interruption of the prevertebral ganglia/splanchnic-spinal axis more strongly attenuated behavioral deficits and -synuclein pathology than vagotomy. In the gastroduodenal PFF model, both vagal and splanchnic-spinal pathways contributed to pathology propagation. Early after PFF inoculation, pathological -synuclein was detected in peripheral neural structures associated with both routes. Consistent with these findings, spinal pathology was evident in human PD. Together, these results identify the splanchnic-spinal pathway as a key component of body-first Parkinson's disease, broadening current models of peripheral-to-central disease progression and informing efforts to target early peripheral disease progression.
ER -