Evidence map›Paper›PMID 37339976›Full record

ArticleNature communications2023

The contribution of inflammatory astrocytes to BBB impairments in a brain-chip model of Parkinson's disease.

A de Rus Jacquet, M Alpaugh, H L Denis, J L Tancredi, M Boutin, J Decaestecker, C Beauparlant, L Herrmann, M Saint-Pierre, M Parent and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
12.9field-weighted citation impact, top 1% of its field
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

72 citing papers in PubMed, 105 citations in OpenAlex.

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12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

A de Rus Jacquet *Centre de Recherche du CHU de Québec - Université Laval, Axe Neurosciences, Québec, QC, G1V 4G2, Canada. aurelie.jacquet@crchudequebec.ulaval.ca.ORCID 0000-0002-5548-8045
M Alpaugh *Centre de Recherche du CHU de Québec - Université Laval, Axe Neurosciences, Québec, QC, G1V 4G2, Canada.
H L DenisCentre de Recherche du CHU de Québec - Université Laval, Axe Neurosciences, Québec, QC, G1V 4G2, Canada.ORCID 0000-0003-1978-5058
J L TancrediJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, 20147, USA.
M BoutinCentre de Recherche du CHU de Québec - Université Laval, Axe Neurosciences, Québec, QC, G1V 4G2, Canada.
J DecaesteckerCentre de Recherche du CHU de Québec - Université Laval, Axe Endocrinologie et Néphrologie, Québec, QC, G1V 4G2, Canada.
C BeauparlantCentre de Recherche du CHU de Québec - Université Laval, Axe Endocrinologie et Néphrologie, Québec, QC, G1V 4G2, Canada.
L HerrmannCentre de Recherche du CHU de Québec - Université Laval, Axe Endocrinologie et Néphrologie, Québec, QC, G1V 4G2, Canada.
M Saint-PierreCentre de Recherche du CHU de Québec - Université Laval, Axe Neurosciences, Québec, QC, G1V 4G2, Canada.
M ParentDépartement de Psychiatrie & Neurosciences, Université Laval, Québec, QC, G1V 0A6, Canada.
A DroitCentre de Recherche du CHU de Québec - Université Laval, Axe Endocrinologie et Néphrologie, Québec, QC, G1V 4G2, Canada.ORCID 0000-0001-7922-790X
S BretonCentre de Recherche du CHU de Québec - Université Laval, Axe Reproduction, santé de la mère et de l'enfant, Québec, QC, G1V 4G2, Canada.
F CicchettiCentre de Recherche du CHU de Québec - Université Laval, Axe Neurosciences, Québec, QC, G1V 4G2, Canada. francesca.cicchetti@crchudequebec.ulaval.ca.ORCID 0000-0001-5490-1961
Université Laval · CAHoward Hughes Medical Institute · USJanelia Research Campus · USOntario Brain Institute · CA

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

Astrocyte dysfunction has previously been linked to multiple neurodegenerative disorders including Parkinson's disease (PD). Among their many roles, astrocytes are mediators of the brain immune response, and astrocyte reactivity is a pathological feature of PD. They are also involved in the formation and maintenance of the blood-brain barrier (BBB), but barrier integrity is compromised in people with PD. This study focuses on an unexplored area of PD pathogenesis by characterizing the interplay between astrocytes, inflammation and BBB integrity, and by combining patient-derived induced pluripotent stem cells with microfluidic technologies to generate a 3D human BBB chip. Here we report that astrocytes derived from female donors harboring the PD-related LRRK2 G2019S mutation are pro-inflammatory and fail to support the formation of a functional capillary in vitro. We show that inhibition of MEK1/2 signaling attenuates the inflammatory profile of mutant astrocytes and rescues BBB formation, providing insights into mechanisms regulating barrier integrity in PD. Lastly, we confirm that vascular changes are also observed in the human postmortem substantia nigra of both males and females with PD.

Indexed as

Blood-Brain BarrierParkinson DiseaseAstrocytesBrainFemaleHumansMaleSubstantia Nigra

Identifiers

PMID37339976
PMCPMC10282096
OpenAlexW4381434187

What Socratic holds

Textmetadata
LicenceCC BY
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.