Evidence map›Paper›PMID 38609392›Full record

ArticleNPJ Parkinson's disease2024

Early deficits in an in vitro striatal microcircuit model carrying the Parkinson's GBA-N370S mutation.

Quyen B Do, Humaira Noor, Ricardo Marquez-Gomez, Kaitlyn M L Cramb, Bryan Ng, Ajantha Abbey, Naroa Ibarra-Aizpurua, Maria Claudia Caiazza, Parnaz Sharifi, Charmaine Lang and 4 more

Open access · goldAbstract read
In one paragraph

Article in NPJ Parkinson's disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.3field-weighted citation impact, top 22% 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, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Frontiers in neuroscience · 2025
    Review
  5. Article
  6. Review
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

14 authors at 3 institutions in 3 countries.

Quyen B DoOxford Parkinson's Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, South Park Road, Oxford, OX1 3QU, UK.ORCID http://orcid.org/0000-0003-4223-0886
Humaira NoorOxford Parkinson's Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, South Park Road, Oxford, OX1 3QU, UK.
Ricardo Marquez-GomezOxford Parkinson's Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, South Park Road, Oxford, OX1 3QU, UK.ORCID http://orcid.org/0000-0002-5810-2670
Kaitlyn M L CrambOxford Parkinson's Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, South Park Road, Oxford, OX1 3QU, UK.ORCID http://orcid.org/0000-0003-2822-7752
Bryan NgOxford Parkinson's Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, South Park Road, Oxford, OX1 3QU, UK.
Ajantha AbbeyOxford Parkinson's Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, South Park Road, Oxford, OX1 3QU, UK.ORCID http://orcid.org/0000-0003-0484-8001
Naroa Ibarra-AizpuruaOxford Parkinson's Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, South Park Road, Oxford, OX1 3QU, UK.
Maria Claudia CaiazzaOxford Parkinson's Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, South Park Road, Oxford, OX1 3QU, UK.ORCID http://orcid.org/0000-0002-0568-964X
Parnaz SharifiOxford Parkinson's Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, South Park Road, Oxford, OX1 3QU, UK.
Charmaine LangOxford Parkinson's Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, South Park Road, Oxford, OX1 3QU, UK.
Dayne Beccano-KellyOxford Parkinson's Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, South Park Road, Oxford, OX1 3QU, UK.ORCID http://orcid.org/0000-0003-3592-8354
Jimena BaleriolaAchucarro Basque Center for Neuroscience, Leioa, Spain.
Nora Bengoa-VergnioryOxford Parkinson's Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, South Park Road, Oxford, OX1 3QU, UK. nora.bv@achucarro.org.ORCID http://orcid.org/0000-0002-3700-0464
Richard Wade-MartinsOxford Parkinson's Disease Centre and Department of Physiology, Anatomy and Genetics, University of Oxford, South Park Road, Oxford, OX1 3QU, UK. richard.wade-martins@dpag.ox.ac.uk.ORCID http://orcid.org/0000-0001-6691-580X
University of Oxford · GBIkerbasque · ESCentre for Human Genetics · GB

Funding

Medical Research Council MR/M024962/1Parkinson's UK J-1403Wellcome Trust
6 · The paper itself

Abstract

Understanding medium spiny neuron (MSN) physiology is essential to understand motor impairments in Parkinson's disease (PD) given the architecture of the basal ganglia. Here, we developed a custom three-chambered microfluidic platform and established a cortico-striato-nigral microcircuit partially recapitulating the striatal presynaptic landscape in vitro using induced pluripotent stem cell (iPSC)-derived neurons. We found that, cortical glutamatergic projections facilitated MSN synaptic activity, and dopaminergic transmission enhanced maturation of MSNs in vitro. Replacement of wild-type iPSC-derived dopamine neurons (iPSC-DaNs) in the striatal microcircuit with those carrying the PD-related GBA-N370S mutation led to a depolarisation of resting membrane potential and an increase in rheobase in iPSC-MSNs, as well as a reduction in both voltage-gated sodium and potassium currents. Such deficits were resolved in late microcircuit cultures, and could be reversed in younger cultures with antagonism of protein kinase A activity in iPSC-MSNs. Taken together, our results highlight the unique utility of modelling striatal neurons in a modular physiological circuit to reveal mechanistic insights into GBA1 mutations in PD.

Identifiers

PMID38609392
PMCPMC11014935
OpenAlexW4394753925

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.