Perineuronal Net Alterations Following Early-Life Stress: Are Microglia Pulling Some Strings?
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Updated: Jun 11, 2025
Author Spotlight: Exploring Microglial Interactions with Stress-Response Circuitry Using the Limited Bedding and Nesting Model
Published on: July 12, 2024
Reza Rahimian1,2, Claudia Belliveau1,3, Sophie Simard1,3
1McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, QC H4H 1R3, Canada.
Abstract:
The extracellular matrix plays a key role in synapse formation and in the modulation of synaptic function in the central nervous system. Recent investigations have revealed that microglia, the resident immune cells of the brain, are involved in extracellular matrix remodeling under both physiological and pathological conditions. Moreover, the dysregulation of both innate immune responses and the extracellular matrix has been documented in stress-related psychopathologies as well as in relation to early-life stress. However, the dynamics of microglial regulation of the ECM and how it can be impacted by early-life adversity have been understudied. This brief review provides an overview of the recent literature on this topic, drawing from both animal model and human post mortem studies. Direct and indirect mechanisms through which microglia may regulate the extracellular matrix-including perineuronal nets-are presented and discussed in light of the interactions with other cell types.
Insights
Microglia, the brain's immune cells, remodel the extracellular matrix (ECM), impacting synapses. Early-life stress may disrupt this process, affecting brain function and potentially leading to psychopathologies.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- The extracellular matrix (ECM) is crucial for synaptic plasticity and function in the central nervous system.
- Microglia, the brain's resident immune cells, actively participate in ECM remodeling.
- Dysregulation of ECM and innate immunity is linked to stress-related disorders and early-life adversity.
Purpose of the Study:
- To review current literature on microglial regulation of the ECM.
- To explore how early-life adversity impacts microglial ECM remodeling.
- To discuss the mechanisms involved in microglial ECM modulation.
Main Methods:
- Literature review synthesizing findings from animal models.
- Analysis of human post-mortem studies.
- Discussion of direct and indirect microglial mechanisms.
Main Results:
- Microglia influence ECM composition and structure, including perineuronal nets.
- Early-life stress can alter microglial-ECM interactions.
- These interactions are complex and involve cross-talk with other brain cells.
Conclusions:
- Microglia play a significant role in ECM dynamics within the central nervous system.
- Understanding microglial-ECM interactions is vital for addressing the neurobiological underpinnings of stress-related psychopathologies.
- Further research is needed to elucidate the precise mechanisms and therapeutic potential.
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