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

Zachary A Colon^1,2, Shannon C Chan^1,3, Kathleen A Maguire-Zeiss^4,5,6

¹School of Medicine, Department of Neuroscience, Georgetown University, Washington, DC, USA.

Journal of Neuroinflammation

|November 19, 2025

Summary

This summary is machine-generated.

Aging causes brain inflammation and memory deficits, altering perineuronal nets (PNNs) in the hippocampus but not the striatum. Neuroinflammation impacts PNNs and behavior, necessitating region-specific treatments.

Keywords:

Hippocampus Inflammaging Neuroinflammation Parvalbumin Striatum

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Area of Science:

Neuroscience
Aging Research
Neuroinflammation

Background:

Aging is linked to cognitive decline, neuroinflammation (inflammaging), and increased risk for neurodegenerative diseases.
Perineuronal nets (PNNs) protect neurons and regulate plasticity, but their role in aging-related neuroinflammation is unclear.
This study investigates age-associated changes in PNNs, glial activation, and neuroinflammation in brain regions affected by neurodegeneration.

Purpose of the Study:

To examine age-related changes in PNN homeostasis, glial activation, and neuroinflammation.
To compare these changes in the hippocampus and dorsal striatum, regions relevant to neurodegenerative diseases.
To understand the relationship between neuroinflammation, PNNs, and cognitive function during aging.

Main Methods:

Aged (22-month) and young (4-month) male mice were assessed for spatial learning, locomotion, and anxiety behaviors.
Immunostaining quantified PNNs, parvalbumin (PV) interneurons, and microglial activation (Iba1) in the hippocampus and dorsal striatum.
Gene expression analysis of inflammatory and extracellular matrix markers was performed using quantitative RT-PCR.

Main Results:

Aged mice showed memory deficits but no changes in locomotion or anxiety.
The hippocampus exhibited increased PNNs and neuroinflammation, while the striatum maintained PNN homeostasis.
Microglial activation and specific inflammatory markers increased with age, with distinct regional patterns and morphological changes in striatal microglia.

Conclusions:

Aging differentially impacts neuroinflammation and PNN integrity across brain regions.
The hippocampus shows PNN accumulation and neuroinflammation correlating with behavioral changes.
The striatum maintains PNN homeostasis despite increased microglial activation, highlighting the need for region-specific therapeutic strategies targeting PNN regulation.