Evidence map›Paper›PMID 40975067›Full record

ArticleImmunity2025

Rod-shaped microglia interact with neuronal dendrites to attenuate cortical excitability during TDP-43-related neurodegeneration.

Manling Xie, Yue Liang, Alessandra S Miller, Praveen N Pallegar, Anthony D Umpierre, Na Wang, Shuwen Zhang, Nagaswaroop Kengunte Nagaraj, Zachary C Fogarty, Nikhil B Ghayal and 9 more

Abstract read
In one paragraph

Article in Immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed.

  1. Immune-mediated excitotoxicity in brain disorders.Nature reviews. Immunology · 2026
    Review
  2. Article
  3. VlPAG/DRN Microglia Drive Neuropathic Pain-Induced Depression via a Defined Neuroimmune Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Review
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  8. Article
  9. Article
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  12. Article
  13. Article
  14. Article
  15. Human microglia differentially respond to β-amyloid, tau, and combined Alzheimer's disease pathologies in vivo.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  16. Network Dysfunction Precedes Neurodegeneration in a dox-Regulatable TDP-43 Mouse Model of ALS-FTD.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  17. Article
  18. Unlocking Disease-Modifying Treatments for TDP-43-Mediated Neurodegeneration.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Manling XieDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Yue LiangCenter for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA.
Alessandra S MillerDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Praveen N PallegarDepartment of Neurology, Mayo Clinic, Rochester, MN, USA; Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA.
Anthony D UmpierreDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Na WangDepartment of Neurology, Mayo Clinic, Rochester, MN, USA; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Shuwen ZhangDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Nagaswaroop Kengunte NagarajDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Zachary C FogartyDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Nikhil B GhayalDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Björn OskarssonDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Shunyi ZhaoDepartment of Neurology, Mayo Clinic, Rochester, MN, USA; Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA.
Jiaying ZhengCenter for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA.
Wu ShiCenter for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA.
Mastura AkterCenter for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA.
Fangfang QiDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Aivi T NguyenDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Long-Jun WuDepartment of Neurology, Mayo Clinic, Rochester, MN, USA; Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA. Electronic address: longjun.wu@uth.tmc.edu.

Funding

Project 4 (Genetic modifiers for APOE-associated Alzheimer's disease pathogenesis)U19AG069701 · NIA · MAYO CLINIC JACKSONVILLE · PI Yingxue Ren · 2021 to 2026
$42.0M
How microglia sense and regulate neuronal activity in the adult brainR35NS132326 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Long-Jun Wu · 2023 to 2026
$3.2M
Microglial regulation of neuronal activity in TDP-43 neurodegenerationRF1AG082314 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI WU, LONG-JUN · 2023 to 2023
$1.9M
Microglial regulation of neuronal activity in TDP-43 neurodegenerationR01AG082314 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Long-Jun Wu · 2026 to 2026
$712k
NIA NIH HHS R01 AG082314NIA NIH HHS RF1 AG082314NIA NIH HHS U19 AG069701NINDS NIH HHS R35 NS132326
6 · The paper itself

Abstract

Microglia, the principal immune cells of the central nervous system, have emerged as important players in sensing and regulating neuronal activity. While microglial activation is a hallmark in neurodegeneration, the specific role of microglia in disease-related cortical excitability remains unknown. Utilizing multichannel probe recordings and longitudinal in vivo calcium imaging, we observed neuronal hyperactivity at the initial stage of disease progression in a mouse model of TAR DNA-binding protein 43 (TDP-43) neurodegeneration (rNLS8, regulated nuclear localization sequence-deleted human TDP-43 transgenic mouse model). Spatial and single-cell RNA sequencing revealed a specific subpopulation of microglia, rod-shaped microglia, with a distinct morphology and direct response to cortical hyperactivity. Rod-shaped microglia predominantly interacted with neuronal dendrites and remodeled excitatory synaptic inputs to attenuate motor cortical hyperactivity. Triggering receptor expressed on myeloid cells 2 (TREM2) deficiency led to a marked reduction of rod-shaped microglia accompanied by increased neuronal activity in rNLS8 mice. Together, our results suggest that rod-shaped microglia play a neuroprotective role by attenuating cortical hyperexcitability in TDP-43-related neurodegeneration.

Indexed as

Cortical ExcitabilityDendritesDNA-Binding ProteinsMicrogliaNeurodegenerative DiseasesAgedAged, 80 and overAnimalsCase-Control StudiesCell CommunicationDisease Models, AnimalElectrodes, ImplantedFemaleGene Knockout TechniquesHumansIntravital MicroscopyDNA-Binding ProteinsMembrane GlycoproteinsReceptors, ImmunologicTARDBP protein, humanTrem2 protein, mouseamyotrophic lateral sclerosiscortical hyperactivityglial biologymotor neuron diseaseneurodegenerationneuroimmunologyrod-shaped microgliaTDP-43Trem2

Identifiers

PMID40975067
PMCPMC12453602

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.