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FcγR- and CD9-dependent synapse-engulfing microglia in the thalamus drive cognitive impairment following cortical brain damage in mice.

Overview

Authors: Ken Matoba1, Takahiro Kochi1,2, Oluwaseun Fatoba1, Md Sorwer Alam Parvez1, Inssaf Berkiks1, Yassin R Mreyoud1, Harrison Strong1, Jana H Badrani1, Hency Patel1, Yoshiko Nagaoka-Kamata3, Masakazu Kamata4,5, Hiroshi Tsujioka6, Toshihide Yamashita6, David K Crossman7, Minae Niwa1,8,9, Shin-ichi Kano1,8
ORCID iDs: Oluwaseun Fatoba, Md Sorwer Alam Parvez, Yassin R Mreyoud, Jana H Badrani, Masakazu Kamata, Hiroshi Tsujioka, Toshihide Yamashita, David K Crossman, Minae Niwa, Shin-ichi Kano
  1. Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL USA
  2. Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
  3. Department of Pathology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL USA
  4. Department of Microbiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL USA
  5. O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL USA
  6. Department of Molecular Neuroscience, Graduate School of Medicine, The University of Osaka, Osaka, Japan
  7. Department of Genetics, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL USA
  8. Department of Neurobiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL USA
  9. Department of Biomedical Engineering, University of Alabama at Birmingham School of Engineering, Birmingham, AL USA
Institutions: University of Alabama at Birmingham (United States); UAB Medicine; National Center of Neurology and Psychiatry (Japan); O'Neal Comprehensive Cancer Center; The University of Osaka (Japan)
Journal: Nature communications, volume 17, issue 1, article 8514
Dates: received 12 March 2026; accepted 5 June 2026; published online 9 July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-74904-1 · PMID 42425959 · PMCID PMC13484472 · OpenAlex W7167807658
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), cellular / molecular (subfield)
Methods: Connectivity, Statistics, Smoothing, state filtering, decompositions, fMRI & imaging
Keywords: Neuroimmunology
MeSH: Brain Injuries*, Cognitive Dysfunction*, Microglia*, Receptors, IgG*, Synapses*, Tetraspanin 29*, Thalamus*, Animals, Blood-Brain Barrier, Disease Models, Animal, Female, Immunoglobulin G, Male, Mice, Mice, Inbred C57BL, Mice, Knockout (* major topic)
Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex
Funding: NIMH NIH HHS (F30 MH139313, T32 MH129274); U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (T32GM008361); U.S. Department of Health & Human Services | NIH | National Institute on Aging (R01AG079129); U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (F30MH139313, T32MH129274); U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) (F30MH139313, T32MH129274); U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics) (P30CA013148); NIA NIH HHS (R01 AG079129); NIGMS NIH HHS (T32 GM008361); NCI NIH HHS (P30 CA013148); U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (P30CA013148); NINDS NIH HHS (R01 NS133242); U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (R01NS133242); NIAID NIH HHS (P30 AI027767); Division of Intramural Research, National Institute of Allergy and Infectious Diseases (P30AI027767); U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) (R01AG079129); U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) (R01NS133242); U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) (T32GM008361)
Citations: cited by 1 paper (Europe PMC); 115 references in the paper

Abstract

Chronic neuroinflammation gives rise to diverse microglial states across the brain, yet how region-specific microglial remodeling contributes to cognitive dysfunction remains unclear. Here we report that synapse-engulfing microglia in the thalamus drive cognitive impairment after cortical brain damage in mice, primarily studied in females. Region-specific manipulations of microglia during the chronic phase show that reactive microglial changes in the thalamus, but not in the hippocampus, impair recognition memory. Single-cell RNA sequencing reveals an enrichment of synapse-engulfing CD9hi microglia in the thalamus. Antibody-based CD9 blockade in the thalamus, as well as microglia-selective CD9 disruption, rescues thalamic synaptic loss, restores neuronal activity, and improves recognition memory. Further analysis shows that the blood-brain barrier disruption and subsequent γ-immunoglobulin (IgG) extravasation facilitate the generation of CD9hi microglia in an Fcγ receptor III-dependent manner. These findings demonstrate that the induction of synapse-engulfing CD9hi microglia in the thalamus by IgG/FcγRIII signaling drives recognition memory deficits following cortical damage.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

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Data

Datasets cited

Data availability

Source data are provided with this paper. scRNA-seq data are available at the NCBI Gene Expression Omnibus under accession numbers GSE200264 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE200264), GSE260805 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE260805), and GSE275711 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275711). Source data are provided with this paper.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 16 authors, 1 keyword, 16 MeSH terms, 17 funders, 115 references.

Cite

This paper

Matoba, K., Kochi, T., Fatoba, O., Parvez, M. S. A., Berkiks, I., Mreyoud, Y. R., Strong, H., Badrani, J. H., Patel, H., Nagaoka-Kamata, Y., Kamata, M., Tsujioka, H., Yamashita, T., Crossman, D. K., Niwa, M., & Kano, S.-i. (2026). FcγR- and CD9-dependent synapse-engulfing microglia in the thalamus drive cognitive impairment following cortical brain damage in mice. Nature communications, 17(1), 8514. https://doi.org/10.1038/s41467-026-74904-1

BibTeX

@article{matoba2026fcr,
author = {Matoba, Ken and Kochi, Takahiro and Fatoba, Oluwaseun and Parvez, Md Sorwer Alam and Berkiks, Inssaf and Mreyoud, Yassin R and Strong, Harrison and Badrani, Jana H and Patel, Hency and Nagaoka-Kamata, Yoshiko and Kamata, Masakazu and Tsujioka, Hiroshi and Yamashita, Toshihide and Crossman, David K and Niwa, Minae and Kano, Shin-ichi},
title = {{FcγR- and CD9-dependent synapse-engulfing microglia in the thalamus drive cognitive impairment following cortical brain damage in mice}},
journal = {Nature communications},
year = {2026},
month = jul,
volume = {17},
number = {1},
pages = {8514},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-74904-1},
url = {https://doi.org/10.1038/s41467-026-74904-1},
pmid = {42425959},
pmcid = {PMC13484472}
}

RIS

TY - JOUR
AU - Matoba, Ken
AU - Kochi, Takahiro
AU - Fatoba, Oluwaseun
AU - Parvez, Md Sorwer Alam
AU - Berkiks, Inssaf
AU - Mreyoud, Yassin R
AU - Strong, Harrison
AU - Badrani, Jana H
AU - Patel, Hency
AU - Nagaoka-Kamata, Yoshiko
AU - Kamata, Masakazu
AU - Tsujioka, Hiroshi
AU - Yamashita, Toshihide
AU - Crossman, David K
AU - Niwa, Minae
AU - Kano, Shin-ichi
TI - FcγR- and CD9-dependent synapse-engulfing microglia in the thalamus drive cognitive impairment following cortical brain damage in mice
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/07/09
VL - 17
IS - 1
SP - 8514
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-74904-1
UR - https://doi.org/10.1038/s41467-026-74904-1
LA - en
ER -

CSL-JSON

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