Evidence map›Paper›PMID 42475878›Full record

ArticleEBioMedicine2026

Neuron-derived neurotrophic factor-positive interneurons: a cellular target for anti-seizure therapies.

Amy Richardson, Marion S Mercier, Yoshiteru Shimoda, Robert T Graham, Marco Leite, Alejandro Garcia, Maud Muller, Suraya A Bond, Maria Grozdanova, Qimin Wu and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Amy RichardsonUCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom. Electronic address: amy-richardson@ucl.ac.uk.
Marion S MercierUCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
Yoshiteru ShimodaUCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
Robert T GrahamUCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
Marco LeiteUCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
Alejandro GarciaUCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
Maud MullerUCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
Suraya A BondUCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
Maria GrozdanovaUCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
Qimin WuUCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
Andreas LiebUCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
Dimitri M KullmannUCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom. Electronic address: d.kullmann@ucl.ac.uk.
Vincent MagloireUCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom. Electronic address: vincent.magloire@inserm.fr.

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundFailure of epilepsy pharmacotherapy is common, justifying efforts to identify optimal cell targets for advanced therapies. Genetic manipulations of the inhibitory system in principle offer a finely tuned intervention that cannot be achieved with a broad reduction of pyramidal neuron excitability. In this context, neuron-derived neurotrophic factor-expressing (NDNF+) interneurons evoke long-lasting GABA

methodsTo address this, we employed calcium imaging, optogenetics, and chemogenetics in an NDNF-Cre mouse line to investigate how NDNF+ interneurons influence cortical and hippocampal hyperactivity and spontaneous seizures.

findingsWe show that NDNF+ interneurons are actively recruited during interictal spikes and focal seizures, although more slowly than parvalbumin-positive interneurons (mean difference: 2.8 s, p = 0.023). Optogenetic hyperpolarisation of NDNF+ interneurons exacerbates epileptic discharges (normalised seizure-duration mean difference: 0.23, p = 0.0474), whereas their depolarisation suppresses focal seizures, even when the optogenetic stimulus is delayed by several seconds from seizure onset (normalized seizure-duration mean difference: -0.27, p = 0.03). This effect is largely mediated by GABA

interpretationCollectively, these findings establish NDNF+ neurons as key regulators of both cortical and hippocampal excitability even during epileptic activity, and identify them as promising cellular targets for the development of anti-seizure therapies.

fundingEpilepsy Research UK, Wellcome, the Medical Research Council, the Gatsby Charitable Foundation, and The Rosetrees Trust.

Indexed as

InterneuronsNerve Growth FactorsSeizuresAnimalsCalciumChemogeneticsDisease Models, AnimalHippocampusMiceMice, TransgenicOptogeneticsPyramidal CellsCalciumNerve Growth FactorsAnti-seizure therapiesEpilepsyInhibitionNDNF+ interneurons

Identifiers

PMID42475878
PMCPMC13393760

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.