Evidence map›Paper›PMID 41525334›Full record

ArticleBrain : a journal of neurology2026

Enhanced mGluR1 function causes motor deficits and region-specific Purkinje cell dysfunction.

Mohamed F Ibrahim, Sevda Boyanova, Yin Chun Cheng, Clemence Ligneul, Rasneer S Bains, Tiffany C Johnpulle, Jason P Lerch, Edward O Mann, Peter L Oliver, Esther B E Becker

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2026. 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. 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.

Mohamed F IbrahimNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Sevda BoyanovaNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Yin Chun ChengNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Clemence LigneulWellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Rasneer S BainsMary Lyon Centre at MRC Harwell, Didcot OX11 0RD, UK.
Tiffany C JohnpulleNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Jason P LerchWellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Edward O MannDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
Peter L OliverMammalian Genetics Unit, MRC Harwell Institute, Didcot OX11 0RD, UK.
Esther B E BeckerNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.ORCID 0000-0002-5238-4902

Funding

Mary Lyon Centre MC_UP_2201/2Mary Lyon Centre MC_UP_2202/1UKRI Medical Research Council MR/P502005/1UKRI Medical Research Council MR/T020474/1Wellcome CentreWellcome TrustWellcome Trust 203139/A/16/ZWellcome Trust 203139/Z/16/Z
6 · The paper itself

Abstract

Spinocerebellar ataxias (SCAs) are autosomal dominantly inherited neurodegenerative disorders with no effective treatment. Aberrant signalling through the metabotropic glutamate receptor (mGluR1) has been implicated in several SCAs. However, whether disease is caused through decreased or increased mGluR1 signalling remains controversial. Here, we generate the first mouse model of enhanced mGluR1 function by introducing a patient gain-of-function mutation (p.Y792C) that causes SCA44 in the metabotropic glutamate receptor 1 (Grm1) gene. Grm1 mutant mice recapitulate key pathophysiological aspects of SCA, including progressive motor deficits, altered climbing fibre innervation and perturbed Purkinje cell (PC) spontaneous activity. We report that changes in synaptic innervation and intrinsic PC activity upon overactive mGluR1 signalling manifest in a lobule- and disease-stage-specific manner. Our findings demonstrate that enhanced mGluR1 function is a direct and specific driver of PC dysfunction and pathology and provide a mechanism for understanding the selective vulnerability of different PC populations in SCA.

Indexed as

Purkinje CellsReceptors, Metabotropic GlutamateSpinocerebellar AtaxiasAnimalsCerebellumDisease Models, AnimalFemaleMaleMiceMice, Inbred C57BLMice, Transgenicmetabotropic glutamate receptor type 1Receptors, Metabotropic GlutamateataxiacerebellumGrm1mGluR1Purkinje cellselective vulnerability

Identifiers

PMID41525334
PMCPMC13431802

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.