Evidence map›Paper›PMID 40482637›Full record

ArticleNeuron2025

Distinct molecular patterns in R6/2 HD mouse brain: Insights from spatiotemporal transcriptomics.

Mara S Burns, Ricardo Miramontes, Jie Wu, Ravinder Gulia, Madhu S Saddala, Alice L Lau, Tiffany Quach, John C Reidling, Vivek Swarup, Albert R La Spada and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Decoding neurodegeneration one cell at a time.The Journal of clinical investigation · 2026
    Review
  6. Article
  7. 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

12 authors.

Mara S BurnsDepartment of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92617, USA.
Ricardo MiramontesInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92617, USA.
Jie WuDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92617, USA.
Ravinder GuliaDepartment of Pathology & Laboratory Medicine, University of California, Irvine, Irvine, CA 92617, USA.
Madhu S SaddalaDepartment of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92617, USA.
Alice L LauDepartment of Psychiatry & Human Behavior, University of California, Irvine, Irvine, CA 92617, USA.
Tiffany QuachDepartment of Pathology & Laboratory Medicine, University of California, Irvine, Irvine, CA 92617, USA; Department of Biomedical Sciences, University of California, San Diego, San Diego, CA 92093, USA.
John C ReidlingInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92617, USA.
Vivek SwarupDepartment of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92617, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92617, USA.
Albert R La SpadaDepartment of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92617, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92617, USA; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92617, USA; Department of Pathology & Laboratory Medicine, University of California, Irvine, Irvine, CA 92617, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92617, USA; Center for Neurotherapeutics, University of California, Irvine, Irvine, CA 92617, USA; Department of Neurology, University of California, Irvine, Irvine, CA 92617, USA.
Ryan G LimInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92617, USA.
Leslie M ThompsonDepartment of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92617, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92617, USA; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92617, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92617, USA; Center for Neurotherapeutics, University of California, Irvine, Irvine, CA 92617, USA; Department of Neurology, University of California, Irvine, Irvine, CA 92617, USA; Department of Psychiatry & Human Behavior, University of California, Irvine, Irvine, CA 92617, USA. Electronic address: lmthomps@uci.edu.

Funding

UC Irvine MODEL-ADU54AG054349 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Kim Green · 2017 to 2026
$71.9M
Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Project 3: Neuropathology of the multi-proteinopathy of c9FTD/ALS.P01NS084974 · NINDS · MAYO CLINIC JACKSONVILLE · PI GENDRON, TANIA FRANCE · 2014 to 2024
$17.6M
Molecular Mechanisms of Pathogenesis in Huntington’s diseaseR35NS116872 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Leslie Michels Thompson · 2020 to 2026
$8.5M
La Spada Outstanding Investigator AwardR35NS122140 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI ALBERT R LA SPADA · 2021 to 2026
$7.2M
Epigenetic Pathology and Therapy in Huntington's DiseaseR01NS089076 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI FRAENKEL, ERNEST, HOUSMAN, DAVID · 2015 to 2024
$4.9M
Oligodendrocyte heterogeneity in Alzheimer' s diseaseRF1AG071683 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI SWARUP, VIVEK, ZHANG, JING · 2021 to 2024
$2.2M
Effect of Mutant HTT on the Development and Maturation of AstrocytesF31NS134306 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI BURNS, MARA · 2024 to 2025
$93k
NCI NIH HHS P30 CA062203NIA NIH HHS RF1 AG071683NIA NIH HHS U54 AG054349NINDS NIH HHS F31 NS134306NINDS NIH HHS P01 NS084974NINDS NIH HHS R01 NS089076NINDS NIH HHS R35 NS116872NINDS NIH HHS R35 NS122140
6 · The paper itself

Abstract

Huntington's disease (HD) is marked by widespread cellular dysregulation. To understand disease mechanisms, we and others have utilized bulk and single-cell transcriptomics, which provide cell-type information but limited spatial information. We used 10× Genomics Visium spatial transcriptomics integrated with matched single-nuclei RNA sequencing (snRNA-seq) in the rapidly progressing HD R6/2 mouse brain (post-natal day 0 [P0], 4 weeks, and 12 weeks). Our data suggest regional, temporal, and cell-type-specific regulatory pathways that establish distinct gene expression changes. Synaptic dysfunction is observed broadly throughout the brain, whereas we observed early dysregulation of the transcription factor 4 (Tcf4) that may drive cortical changes. Mitochondrial deficits are the earliest changes, beginning at P0 in the striatum. Striatal identity genes show early increased expression that becomes progressively downregulated. Finally, we identified a time-dependent dysregulation of neuropeptide Y signaling and potential interaction with the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway, which may be involved in the imbalance between Drd1 and Drd2 neuron vulnerability.

Indexed as

BrainHuntington DiseaseTranscriptomeAnimalsCorpus StriatumDisease Models, AnimalGene Expression ProfilingMaleMiceMice, TransgenicReceptors, Dopamine D2Receptors, Dopamine D2cell-cell signalingHuntington’s diseasemetabolismneuropeptide Yprotein kinase AR62 transgenicsnRNA-seqspatial transcriptomicstranscriptional dysregulationtranscription factor 4

Identifiers

PMID40482637
PMCPMC12279385

What OpenQuestion holds

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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.