Evidence map›Paper›PMID 40273372›Full record

ArticleNeurogastroenterology and motility2025

Sex Specific Effects of Environmental Toxin-Derived Alpha Synuclein on Enteric Neuronal-Epithelial Interactions.

Hayley N Templeton, Alexis T Ehrlich, Luke A Schwerdtfeger, Julietta A Sheng, Ronald B Tjalkens, Stuart A Tobet

Abstract read
In one paragraph

Article in Neurogastroenterology and motility, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Enteric glia, neuropeptides, and Parkinson's: impacts of calcitonin gene-related peptide on gut alpha synuclein.American journal of physiology. Gastrointestinal and liver physiology · 2026
    Article
  3. Gut neuropeptide involvement in Parkinson's disease.American journal of physiology. Gastrointestinal and liver physiology · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Hayley N TempletonDepartment of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.ORCID https://orcid.org/0009-0009-4242-4120
Alexis T EhrlichDepartment of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
Luke A SchwerdtfegerAnn Romney Center for Neurological Disease, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Julietta A ShengDepartment of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
Ronald B TjalkensDepartment of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado, USA.
Stuart A TobetDepartment of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.

Funding

Sex Differences in Major Depression, Part II: Impact of Prenatal Immune, Autonomic and Neurovascular FunctionU54MH118919 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI JILL M GOLDSTEIN · 2020 to 2026
$12.7M
Deciphering innate immune signaling mechanisms in glial cells linking lifetime environmental exposures to neuroinflammation, protein aggregation and neurodegeneration in Parkinsons diseaseR35ES035043 · NIEHS · COLORADO STATE UNIVERSITY · PI RONALD TJALKENS · 2023 to 2026
$4.4M
NIEHS NIH HHS R35 ES035043NIMH NIH HHS U54 MH118919
6 · The paper itself

Abstract

backgroundParkinson's Disease (PD) is a neurodegenerative disorder with prodromal gastrointestinal (GI) issues often emerging decades before motor symptoms. Pathologically, PD can be driven by the accumulation of misfolded alpha synuclein (aSyn) protein in the brain and periphery, including the GI tract. Disease epidemiology differs by sex, with men twice as likely to develop PD. Women, however, experience faster disease progression, higher mortality, and more severe GI symptoms. Gut calcitonin gene-related peptide (CGRP) is a key regulator of intestinal contractions and visceral pain. The current study tests the hypothesis that sex differences in GI symptomatology in PD are the result of aSyn aggregation altering enteric CGRP signaling pathways.

methodsTo facilitate peripheral aSyn aggregation, the pesticide rotenone was administered intraperitoneally once daily for 2 weeks to male and female mice. Mice were sacrificed 2 weeks after the last rotenone injection, and immunohistochemistry was performed on sections of proximal colon. KEY

resultsLevels of aSyn were heightened in PGP9.5 immunoreactive myenteric plexus neurons, a subset of which were immunoreactive to CGRP and showed a similar increase in aSyn immunoreactivity in rotenone-treated mice. Female mice exhibited 153% more myenteric aSyn, 26% more apical CGRP immunoreactivity in the mucosa, and 66.7% more aSyn in apical CGRP

conclusionsThis study used a mouse model of PD to uncover sex-specific alterations in enteric neuronal and epithelial populations, underscoring the importance of considering sex as a biological variable while investigating prodromal GI symptoms.

Indexed as

alpha-SynucleinEnteric Nervous SystemIntestinal MucosaNeuronsSex CharacteristicsAnimalsCalcitonin Gene-Related PeptideFemaleMaleMiceMice, Inbred C57BLMyenteric PlexusRotenonealpha-SynucleinCalcitonin Gene-Related PeptideRotenonealpha synucleincalcitonin gene related peptide (CGRP)goblet cellsParkinson's diseasesex differences

Identifiers

PMID40273372
PMCPMC12163210

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.