Evidence map›Paper›PMID 37321222›Full record

ArticleNeuron2023

Early molecular layer interneuron hyperactivity triggers Purkinje neuron degeneration in SCA1.

Federica Pilotto, Christopher Douthwaite, Rim Diab, XiaoQian Ye, Zahraa Al Qassab, Christoph Tietje, Meriem Mounassir, Adolfo Odriozola, Aishwarya Thapa, Ronald A M Buijsen and 8 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 4 institutions in 3 countries.

Federica PilottoDepartment of Neurology, Inselspital University Hospital, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland.
Christopher DouthwaiteInstitute of Clinical Neuroimmunology, Klinikum der Universität München, Ludwig-Maximilians University Munich, Martinsried, Germany.
Rim DiabDepartment of Neurology, Inselspital University Hospital, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland.
XiaoQian YeInstitute of Clinical Neuroimmunology, Klinikum der Universität München, Ludwig-Maximilians University Munich, Martinsried, Germany.
Zahraa Al QassabDepartment of Neurology, Inselspital University Hospital, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland.
Christoph TietjeInstitute of Clinical Neuroimmunology, Klinikum der Universität München, Ludwig-Maximilians University Munich, Martinsried, Germany.
Meriem MounassirInstitute of Clinical Neuroimmunology, Klinikum der Universität München, Ludwig-Maximilians University Munich, Martinsried, Germany.
Adolfo OdriozolaInstitute of Anatomy, University of Bern, Bern, Switzerland.
Aishwarya ThapaDepartment of Neurology, Inselspital University Hospital, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland.
Ronald A M BuijsenDepartment of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Sophie LagacheProteomics and Mass Spectrometry Core Facility, Department for BioMedical Research, University of Bern, Bern, Switzerland.
Anne-Christine UldryProteomics and Mass Spectrometry Core Facility, Department for BioMedical Research, University of Bern, Bern, Switzerland.
Manfred HellerProteomics and Mass Spectrometry Core Facility, Department for BioMedical Research, University of Bern, Bern, Switzerland.
Stefan MüllerFlow Cytometry and Cell sorting, Department for BioMedical Research, University of Bern, Bern, Switzerland.
Willeke M C van Roon-MomDepartment of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Benoît ZuberInstitute of Anatomy, University of Bern, Bern, Switzerland.
Sabine LiebscherInstitute of Clinical Neuroimmunology, Klinikum der Universität München, Ludwig-Maximilians University Munich, Martinsried, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; University Hospital Cologne, Deptartment of Neurology, Cologne, Germany. Electronic address: sabine.liebscher@med.uni-muenchen.de.
Smita SaxenaDepartment of Neurology, Inselspital University Hospital, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland. Electronic address: smita.saxena@dbmr.unibe.ch.
University of Bern · CHLudwig-Maximilians-Universität München · DELeiden University Medical Center · NLMunich Cluster for Systems Neurology · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Toxic proteinaceous deposits and alterations in excitability and activity levels characterize vulnerable neuronal populations in neurodegenerative diseases. Using in vivo two-photon imaging in behaving spinocerebellar ataxia type 1 (Sca1) mice, wherein Purkinje neurons (PNs) degenerate, we identify an inhibitory circuit element (molecular layer interneurons [MLINs]) that becomes prematurely hyperexcitable, compromising sensorimotor signals in the cerebellum at early stages. Mutant MLINs express abnormally elevated parvalbumin, harbor high excitatory-to-inhibitory synaptic density, and display more numerous synaptic connections on PNs, indicating an excitation/inhibition imbalance. Chemogenetic inhibition of hyperexcitable MLINs normalizes parvalbumin expression and restores calcium signaling in Sca1 PNs. Chronic inhibition of mutant MLINs delayed PN degeneration, reduced pathology, and ameliorated motor deficits in Sca1 mice. Conserved proteomic signature of Sca1 MLINs, shared with human SCA1 interneurons, involved the higher expression of FRRS1L, implicated in AMPA receptor trafficking. We thus propose that circuit-level deficits upstream of PNs are one of the main disease triggers in SCA1.

Indexed as

Purkinje CellsSpinocerebellar AtaxiasAnimalsAtaxin-1CerebellumDisease Models, AnimalHumansInterneuronsMembrane ProteinsMiceMice, TransgenicNerve DegenerationNerve Tissue ProteinsParvalbuminsProteomicsAtaxin-1FRRS1L protein, humanMembrane ProteinsNerve Tissue ProteinsParvalbuminscerebellar circuitchemogeneticscircuit modulationexcitation/inhibitionGABAergic neuronsin vivo imagingiPSCsmolecular layer interneurons, spinocerebellar ataxia type 1mouse modelsneurodegenerative diseasePurkinje neurons

Identifiers

PMID37321222
PMCPMC10431915
OpenAlexW4380853957

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.