CoChat
Sign Up
Cited by 308Parkinson's Disease Mechanisms and TreatmentsGastrointestinal motility and disordersNuclear Receptors and Signaling

The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.

Progression of intestinal permeability changes and alpha-synuclein expression in a mouse model of Parkinson's disease

Open access
Kelly, Leo P., Carvey, Paul M., Keshavarzian, Ali, Shannon, Kathleen M., Shaikh, Maliha, Bakay, Roy A. E., Kordower, Jeffrey H.·2014·Movement Disorders
DOI 10.1002/mds.25736PMC PMC4050039
Open this paper in CoChat — free account

Abstract

Parkinson's disease (PD) is a multifocal degenerative disorder for which there is no cure. The majority of cases are sporadic with unknown etiology. Recent data indicate that untreated patients with de novo PD have increased colonic permeability and that both de novo and premotor patients have pathological expression of α‐synuclein (α‐syn) in their colon. Both endpoints potentially can serve as disease biomarkers and even may initiate PD events through gut‐derived, lipopolysaccharide (LPS)‐induced neuronal injury. Animal models could be ideal for interrogating the potential role of the intestines in the pathogenesis of PD; however, few current animal models of PD encompass these nonmotor features. We sought to establish a progressive model of PD that includes the gastrointestinal (GI) dysfunction present in human patients. C57/BL6 mice were systemically administered one dose of either LPS (2.5 mg/kg) or saline and were sacrificed in monthly intervals (n = 5 mice for 5 months) to create a time‐course. Small and large intestinal permeability was assessed by analyzing the urinary output of orally ingested sugar probes through capillary column gas chromatography. α‐Syn expression was assessed by counting the number of mildly, moderately, and severely affected myenteric ganglia neurons throughout the GI tract, and the counts were validated by quantitative optical density measurements. Nigrostriatal integrity was assessed by tyrosine hydroxylase immunohistochemistry stereology and densitometry. LPS caused an immediate and progressive increase in α‐syn expression in the large intestine but not in the small intestine. Intestinal permeability of the whole gut (large and small intestines) progressively increased between months 2 and 4 after LPS administration but returned to baseline levels at month 5. Selective measurements demonstrated that intestinal permeability in the small intestine remained largely intact, suggesting that gut leakiness was predominately in the large intestine. Phosphorylated serine 129‐α‐syn was identified in a subset of colonic myenteric neurons at months 4 and 5. Although these changes were observed in the absence of nigrostriatal degeneration, an abrupt but insignificant increase in brainstem α‐syn was observed that paralleled the restoration of permeability. No changes were observed over time in controls. LPS, an endotoxin used to model PD, causes sequential increases in α‐syn immunoreactivity, intestinal permeability, and pathological α‐syn accumulation in the colon in a manner similar to that observed in patients with PD. These features are observed without nigrostriatal degeneration and incorporate PD features before the motor syndrome. This allows for the potential use of this model in testing neuroprotective and disease‐modifying therapies, including intestinal‐directed therapies to fortify intestinal barrier integrity. © 2013 International Parkinson and Movement Disorder Society

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/mds.25736

Cites

61 of 61 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Show all 61 references

Research works printed but not linked: 2

  1. Bing G, 1998, Microglia mediated dopaminergic cell death in the substantia nigra: a new animal model for Parkinson's disease [abstract], Neurosci Abstracts, 24, 44
  2. 10.1016/S1353-8020(11)70062-1 · DOI

Cited by

Sorted by citations

Items 201–300 of 308

Related

See all

Metadata

Authors
Kelly, L. P., Carvey, P. M., Keshavarzian, A., Shannon, K. M., Shaikh, M., Bakay, R. A. E., & Kordower, J. H.
Affiliations
  • Rush University (US)
  • Utrecht University (NL)
Corresponding author
Kordower, Jeffrey H.
ORCID
Venue
Movement Disorders
Publisher
Wiley
Published
2013-11-04
Volume
29
Issue
8
Pages
999-1009
ISSN
  • 0885-3185 (ISSN-L)
  • 1531-8257
DOI
10.1002/mds.25736
PMC
PMC4050039
OpenAlex
W2108108635
Cited by
308
References
61
Citations by year
2026: 11 · 2025: 21 · 2024: 28 · 2023: 55 · 2022: 34 · 2021: 54 · 2020: 29 · 2019: 24 · 2018: 18 · 2017: 13 · 2016: 6 · 2015: 9 · 2014: 6
FWCI
4.44
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Movement Disorders (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01NS055143)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords
Parkinson's disease, intestinal permeability, alpha-synuclein, lipopolysaccharide, gastrointestinal dysfunction, nigrostriatal degeneration, tyrosine hydroxylase, disease biomarkers, mouse model, gut-brain axis
MeSH terms
Animals, Brain, Chromatography, Gas, Colon, Disease Models, Animal, Gastrointestinal Agents, Male, Mice, Inbred C57BL, Parkinson Disease, Permeability, Polysaccharides, Severity of Illness Index, Time Factors, Tyrosine 3-Monooxygenase, Vagus Nerve, Linear Models, Disease Progression, Mice, alpha-Synuclein

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review