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Developmental scarcity induces sex differences in social recognition and CA2 perineuronal nets
Renée C Waters1, Isha R Gore1, Casey J Brown1
1Princeton Neuroscience Institute, Princeton University, Princeton NJ USA.
Biorxiv : the Preprint Server for Biology
|January 16, 2026
Summary
Early life stress impairs social recognition in male mice, linked to brain changes. Targeted intervention in adulthood can reverse these effects, offering hope for recovery.
Area of Science:
- Neuroscience
- Developmental Psychology
- Behavioral Biology
Background:
- Early-life adversity negatively impacts social behavior across species.
- Sex differences in stress responses are observed, but mechanisms are unclear.
- Perineurotoneal nets (PNNs) in the hippocampus regulate plasticity and social behavior.
Purpose of the Study:
- Investigate sex differences in social behavior following early-life adversity.
- Examine the role of hippocampal perineuronal nets in mediating these effects.
- Determine if targeting perineuronal nets can restore social function.
Main Methods:
- Utilized the limited bedding and nesting paradigm in mice to model developmental scarcity.
- Assessed social recognition and novelty preference in adult male and female mice.
- Quantified perineuronal net intensity in the CA2 region of the hippocampus.
- Performed focal degradation of extracellular matrix in the CA2 region.
Main Results:
- Adult males exhibited impaired social recognition, while females showed intact recognition and enhanced novelty preference.
- Increased perineuronal net intensity was observed in the CA2 region of adult males exposed to early stress.
- Degradation of CA2 perineuronal nets restored social recognition in stressed adult males.
Conclusions:
- Early-life adversity induces sex-specific social behavior deficits in mice.
- Hippocampal perineuronal nets in males are implicated in mediating the long-term effects of early stress.
- Targeting perineuronal nets in adulthood presents a potential therapeutic strategy for reversing stress-induced social deficits.
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