Evidence mapPaperPMID 41254697Full record

ArticleJournal of neuroinflammation2025

Age-related inflammatory changes and perineuronal net dynamics: implications for aging.

Zachary A Colon, Shannon C Chan, Kathleen A Maguire-Zeiss

Abstract read
In one paragraph

Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors.

Zachary A ColonSchool of Medicine, Department of Neuroscience, Georgetown University, Washington, DC, USA.
Shannon C ChanSchool of Medicine, Department of Neuroscience, Georgetown University, Washington, DC, USA.
Kathleen A Maguire-ZeissSchool of Medicine, Department of Neuroscience, Georgetown University, Washington, DC, USA. kathleen.maguirezeiss@georgetown.edu.

Funding

Training in Neural Injury &PlasticityT32NS041218 · NINDS · GEORGETOWN UNIVERSITY · PI MARK P BURNS, Kathleen Anne Maguire-Zeiss · 2001 to 2026
$3.5M
Perineuronal proteolysis and circuit dysfunction in HANDR01NS108810 · NINDS · GEORGETOWN UNIVERSITY · PI CONANT, KATHERINE E, MAGUIRE-ZEISS, KATHLEEN ANNE · 2018 to 2022
$1.9M
Pharmacological Sciences Training Program (PSTP)T32GM142520 · NIGMS · GEORGETOWN UNIVERSITY · PI Patrick Alexander Forcelli, Anton Wellstein · 2022 to 2026
$1.3M
NIGMS NIH HHS T32 GM142520NIH HHS R01NS108810NIH HHS T32GM142520NIH-NINDS T32NS041218NINDS NIH HHS R01 NS108810NINDS NIH HHS T32 NS041218
6 · The paper itself

Abstract

backgroundHealthy aging alone can lead to cognitive decline, decreased brain size, protein aggregation, accumulation of senescent cells and neuroinflammation. Furthermore, age is the primary risk factor for several neurodegenerative disorders such as Parkinson's and Alzheimer's disease. Age-related neuroinflammation, as known as inflammaging, is thought to restrict brain plasticity. Perineuronal nets (PNNs), specialized extracellular matrix structures surrounding fast-spiking parvalbumin (PV) interneurons, regulate plasticity and protect neurons from oxidative stress. Given the known impact of inflammaging on neural circuits, this study examines age-associated changes in PNN homeostasis, glial activation, and neuroinflammation in two brain regions relevant to age-related neurodegenerative diseases.

methodsWe analyzed young (4-month-old) and aged (22-month-old) C57BL/6J male mice for several behavioral phenotypes [hippocampal-dependent spatial learning using the Barnes maze; locomotion and anxiety-related behaviors using Open field and T-maze]. Using immunostaining, PNNs (Wisteria floribunda agglutinin and aggrecan), PV interneurons, and microglial activation (Iba1) were quantified in both the hippocampus and dorsal striatum. Glial morphology was examined using a battery of cell body, branching, and endpoint analyses. Quantitative RT-PCR was used to analyze changes in the gene expression of inflammatory and extracellular matrix markers.

resultsAged mice exhibited hippocampal-dependent memory deficits without alterations in locomotion or anxiety-related behavior. PNN counts increased in the aged hippocampus, particularly in CA2, with a higher proportion of WFA

conclusionsThese findings suggest that aging differentially affects neuroinflammation and PNN integrity across brain regions. The hippocampus exhibits PNN accumulation, neuroinflammation, and behavioral changes, whereas the striatum maintains PNN homeostasis concurrent with increased microglial activation. This work suggests that neuroinflammation contributes to age-related changes in PNNs and behavior underscoring the importance of region-specific therapeutic strategies targeting PNN regulation.

Indexed as

AgingExtracellular MatrixHippocampusInflammationNerve NetNeuroinflammatory DiseasesAnimalsMaleMaze LearningMiceMice, Inbred C57BLParvalbuminsParvalbuminsHippocampusInflammagingNeuroinflammationParvalbuminStriatum

Identifiers

PMID41254697
PMCPMC12628600

What Socratic 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 Socratic graph.