Evidence map›Paper›PMID 41309656›Full record

ArticleNature communications2025

Midbrain extracellular matrix and microglia are associated with cognition in aging mice.

Daniel T Gray, Abigail Gutierrez, Yasaman Jami-Alahmadi, Vijaya Pandey, Lin Pan, Ye Zhang, James A Wohlschlegel, Ross A McDevitt, Lindsay M De Biase

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Daniel T GrayDepartment of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. dtgray@mednet.ucla.edu.ORCID http://orcid.org/0000-0001-6262-5178
Abigail GutierrezDepartment of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Yasaman Jami-AlahmadiDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Vijaya PandeyDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Lin PanDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Ye ZhangDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
James A WohlschlegelDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-3399-901X
Ross A McDevittComparative Medicine Section, National Institute on Aging - Intramural Research Program, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-3722-9047
Lindsay M De BiaseDepartment of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. ldebiase@mednet.ucla.edu.ORCID http://orcid.org/0000-0003-0177-5601

Funding

UCLA IDDRC: Translational CoreP50HD103557 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Peyman Golshani, SUMA JACOB · 2020 to 2026
$9.6M
Targeting autophagy to reduce inflammasome-mediated inflammation and immune dysfunction in HIV and methamphetamine useR01DA059873 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Jennifer Fulcher, Ye Zhang · 2024 to 2026
$2.1M
Microglial lysosomes and selective neuronal vulnerabilityR01AG075909 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Lindsay Mitchell De Biase · 2022 to 2026
$1.9M
Molecular characterization of reactive astrocytes in humansR01NS109025 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZHANG, YE · 2018 to 2022
$1.7M
American Federation for Aging Research (American Federation for Aging Research, Inc.) MCKNIGHT21003NIA NIH HHS R01 AG075909NICHD NIH HHS P50 HD103557NIDA NIH HHS R01 DA059873NINDS NIH HHS R01 NS109025Simons Foundation SFI-AN-NC-AB-Independence Postdoctoral-00007445U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) P50HD103557U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) 1R01AG075909-01U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) R01DA059873
6 · The paper itself

Abstract

Synapse dysfunction is tightly linked to cognitive changes during aging. Emerging evidence suggests that microglia and the extracellular matrix (ECM) can potently regulate synapse integrity and plasticity. Yet the brain ECM, and its relationship with microglia, synapses, and cognition during aging remains virtually unexplored. In this study we combine ECM-optimized proteomic workflows with histological analyses in aging mice and discover regional differences in ECM composition and aging-induced ECM remodeling across basal ganglia nuclei. Moreover, we combine two distinct behavioral classification strategies with fixed-tissue confocal imaging and proteomic analysis and identify relationships between the hyaluronan- and proteoglycan-rich ECM and cognitive aging phenotypes. Finally, we provide evidence that aging midbrain microglia lose capacity to interact with and regulate the ECM, and that these aging-associated microglial changes are accompanied by local ECM accumulation and worse behavioral performance. Together, these observations indicate that changing microglia-ECM-synapse interactions contribute to cognitive functioning during healthy aging.

Indexed as

AgingCognitionExtracellular MatrixMesencephalonMicrogliaAnimalsHyaluronic AcidMaleMiceMice, Inbred C57BLProteoglycansProteomicsSynapsesHyaluronic AcidProteoglycans

Identifiers

PMID41309656
PMCPMC12722224

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.