ArticleJournal of neuroinflammation2025
Age-related inflammatory changes and perineuronal net dynamics: implications for aging.
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.
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3 citing papers in PubMed.
- Glial cell and perineuronal net interactions in the dorsal striatum of aged mice.bioRxiv : the preprint server for biology · 2026Article
- Glial Cell and Perineuronal Net Interactions in the Dorsal Striatum of Aged Mice.Journal of experimental neurology · 2026Article
- APOE4 and doxorubicin impair inhibitory interneuron function and homeostatic regulation in the entorhinal cortex.PloS one · 2026Article
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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.
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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.