Evidence map›Paper›PMID 37609821›Full record

ArticleEMBO molecular medicine2023

Metformin rescues migratory deficits of cells derived from patients with periventricular heterotopia.

Cedric Bressan, Marta Snapyan, Marina Snapyan, Johannes Klaus, Francesco di Matteo, Stephen P Robertson, Barbara Treutlein, Martin Parent, Silvia Cappello, Armen Saghatelyan

Open access · goldAbstract read
In one paragraph

Article in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
0.1field-weighted citation impact, top 53% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 1 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
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

10 authors at 5 institutions in 3 countries.

Cedric BressanCERVO Brain Research Center, Quebec City, QC, Canada.ORCID 0000-0001-8820-0354
Marta SnapyanCERVO Brain Research Center, Quebec City, QC, Canada.
Marina SnapyanCERVO Brain Research Center, Quebec City, QC, Canada.
Johannes KlausMax Planck Institute of Psychiatry, Munich, Germany.
Francesco di MatteoMax Planck Institute of Psychiatry, Munich, Germany.
Stephen P RobertsonDunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Barbara TreutleinMax Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.ORCID 0000-0002-3299-5597
Martin ParentCERVO Brain Research Center, Quebec City, QC, Canada.ORCID 0000-0002-0868-1010
Silvia CappelloMax Planck Institute of Psychiatry, Munich, Germany.ORCID 0000-0003-1553-6775
Armen SaghatelyanCERVO Brain Research Center, Quebec City, QC, Canada.ORCID 0000-0003-4962-0465
Max Planck Institute of Psychiatry · DEUniversity of Ottawa · CAOntario Brain Institute · CAMax Planck Institute of Molecular Cell Biology and Genetics · DEUniversity of Otago · NZ

Funding

E-Rare (ERA-Net for Research Programmes on Rare Diseases) HETEROMICS | 01GM1914Gouvernement du Canada | Canadian Institutes of Health Research (IRSC) PJT-114700Gouvernement du Canada | Canadian Institutes of Health Research (IRSC) PJT-159733
6 · The paper itself

Abstract

Periventricular neuronal heterotopia (PH) is one of the most common forms of cortical malformation in the human cortex. We show that human neuronal progenitor cells (hNPCs) derived from PH patients with a DCHS1 or FAT4 mutation as well as isogenic lines had altered migratory dynamics when grafted in the mouse brain. The affected migration was linked to altered autophagy as observed in vivo with an electron microscopic analysis of grafted hNPCs, a Western blot analysis of cortical organoids, and time-lapse imaging of hNPCs in the presence of bafilomycin A1. We further show that deficits in autophagy resulted in the accumulation of paxillin, a focal adhesion protein involved in cell migration. Strikingly, a single-cell RNA-seq analysis of hNPCs revealed similar expression levels of autophagy-related genes. Bolstering AMPK-dependent autophagy by metformin, an FDA-approved drug, promoted migration of PH patients-derived hNPCs. Our data indicate that transcription-independent homeostatic modifications in autophagy contributed to the defective migratory behavior of hNPCs in vivo and suggest that modulating autophagy in hNPCs might rescue neuronal migration deficits in some forms of PH.

Indexed as

Cell MovementMetforminNeural Stem CellsPeriventricular Nodular HeterotopiaAnimalsAutophagyHumansMiceMetforminautophagyDCHS1FAT4human neural progenitor cellsperiventricular neuronal heterotopia

Identifiers

PMID37609821
PMCPMC10565636
OpenAlexW4386084006

What OpenQuestion 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 OpenQuestion graph.