Evidence map›Paper›PMID 41270748›Full record

ArticleStem cell reports2025

Hypersynchronous iPSC-derived SHANK2 neuronal networks are rescued by mGluR5 agonism.

Fraser P McCready, Kartik S Pradeepan, Milad Khaki, Wei Wei, Marta Guevara-Ferrer, Nicole Matusiak, Britney Feng, Alina Piekna, Julio Martinez-Trujillo, James Ellis

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

10 authors.

Fraser P McCreadyDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Developmental, Stem Cell & Cancer Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Kartik S PradeepanDepartment of Physiology and Pharmacology, Department of Psychiatry, Robarts Research and Brain and Mind Institutes, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5B7, Canada.
Milad KhakiDepartment of Physiology and Pharmacology, Department of Psychiatry, Robarts Research and Brain and Mind Institutes, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5B7, Canada.
Wei WeiDevelopmental, Stem Cell & Cancer Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Marta Guevara-FerrerDevelopmental, Stem Cell & Cancer Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Nicole MatusiakDevelopmental, Stem Cell & Cancer Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Britney FengDevelopmental, Stem Cell & Cancer Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Alina PieknaDevelopmental, Stem Cell & Cancer Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Julio Martinez-TrujilloDepartment of Physiology and Pharmacology, Department of Psychiatry, Robarts Research and Brain and Mind Institutes, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5B7, Canada.
James EllisDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Developmental, Stem Cell & Cancer Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada. Electronic address: jellis@sickkids.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Variants in the SHANK2 gene, linked to neurodevelopmental disorders like autism, were studied using human iPSC-derived neurons and multielectrode arrays. We compared two isogenic pairs of SHANK2 cell lines and found that SHANK2 networks exhibited a hyperconnectivity phenotype at the network level. These networks showed a significantly increased frequency and reduced duration of network burst events compared to controls. SHANK2 network activity was hypersynchronous, with stronger functional correlations between recording channels. Spikes within SHANK2 network bursts formed high-frequency trains, creating a distinctive burst shape. Calcium-dependent reverberating super bursts (RSBs) were common in control networks but rare in SHANK2 networks. Treatment with the group 1 mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) fully rescued SHANK2 network hypersynchrony, restored RSB detection, and improved network burst frequency and duration. The findings demonstrate that SHANK2 variants cause functional hyperconnectivity, which can be rescued by pharmacologically regulating glutamatergic neurotransmission.

Indexed as

Induced Pluripotent Stem CellsNerve NetNerve Tissue ProteinsNeuronsReceptor, Metabotropic Glutamate 5Action PotentialsCell LineHumansSynaptic TransmissionNerve Tissue ProteinsReceptor, Metabotropic Glutamate 5SHANK2 protein, humanautism spectrum disorderhypersynchronyiPSCmultielectrode arraysneuronal networksreverberating superburstsSHANK2

Identifiers

PMID41270748
PMCPMC12744861

What OpenQuestion holds

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Registered trials

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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.