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Updated: Sep 12, 2025
Chronic Social Defeat Stress in Early Adolescent Male Mice
Published on: January 24, 2025
Early Life Social Isolation Dysregulates Social Reward Processing, BDNF Signaling, and Intracellular Vesicular
M Di Trapano1,2, V Buzzelli1, B Rizzi2,3
1Department of Science, Section of Biomedical Sciences and Technologies, Roma Tre University, Rome, Italy.
Insights
Early-life social isolation impairs social reward processing in male rats by altering brain BDNF signaling. Females show different neurobiological responses, indicating sex-specific effects of early adversity on social behavior and neuroplasticity.
Area of Science:
- Neuroscience
- Developmental Psychology
- Molecular Biology
Background:
- Early-life social deprivation negatively impacts brain development and behavior.
- Understanding sex-dependent vulnerability to social stressors is crucial for neuropsychiatric disorder research.
- The nucleus accumbens (NAc) is a key brain region for social behavior and reward processing.
Purpose of the Study:
- To investigate the effects of early-life social isolation (ESI) on social and depressive-like behaviors in male and female rats.
- To explore the molecular mechanisms, specifically the BDNF system in the NAc, underlying sex-dependent responses to ESI.
- To determine long-lasting effects of ESI on neurobehavioral maturation and neuroplasticity.
Main Methods:
- Implemented an ESI protocol involving repeated social isolation from postnatal day 14-21 in rats.
- Assessed social and depressive-like behaviors in adolescent and adult male and female rats.
- Analyzed the BDNF/TrkB signaling pathway and endocytic-recycling mechanisms (Rab5-Rab11) in the NAc.
Main Results:
- ESI impaired social reward processing in male rats, with no significant effects on general social or depressive-like behaviors in either sex.
- Males showed ESI-induced downregulation of BDNF signaling and altered Rab5-Rab11 mediated endocytic-recycling in the NAc, suggesting reduced neuroplasticity.
- Females exhibited increased BDNF signaling and enhanced early endosome-recycling mechanisms in response to ESI.
Conclusions:
- Early-life social isolation leads to sex-specific, long-lasting alterations in social reward processing and neurobiological pathways in rats.
- Male rats display deficits in social reward processing linked to reduced BDNF signaling and neuroplasticity in the NAc.
- Distinct molecular mechanisms in the NAc mediate sex-specific responses to early-life stress, offering insights into differential vulnerability to social adversity.
Abstract:
Early-life social deprivation negatively impacts brain development and behavior, increasing susceptibility to neuropsychiatric disorders. In social species such as rats, interactions with the mother and conspecifics are crucial for offspring survival and proper neurobehavioral maturation. However, the mechanisms underlying sex-dependent vulnerability to early-life social stressors, such as social isolation, remain unclear. This study aimed to (i) investigate the effects of early-life social isolation (ESI) on social and depressive-like behaviors in female and male rats during adolescence and adulthood and (ii) explore the molecular mechanisms involved, focusing on the BDNF system in the nucleus accumbens (NAc), a key brain region for social behavior and reward processing. To this aim, we implemented an ESI protocol involving brief periods of repeated social isolation from postnatal day (PND) 14-21 to mimic an adverse early social environment, and then we tested female and male rats across development (i.e., during adolescence and adulthood). Our findings revealed that ESI impaired social reward processing in male rats, whereas general social and depressive-like behaviors remained unaffected in both sexes. These behavioral deficits were accompanied by sex-dependent effects on the BDNF/TrkB signaling pathway in the NAc. Specifically, males exhibited a persistent ESI-induced downregulation of BDNF signaling paralleled by alterations in endocytic-recycling mechanisms mediated by Rab5-Rab11, suggesting increased TrkB sorting and reduced neuroplasticity. Conversely, females showed increased BDNF signaling and enhanced early endosome-recycling mechanisms. These results suggest that male and female rats rely on distinct neurobiological mechanisms to modulate reward processing in response to early-life stress. Overall, our study highlights sex-specific, long-lasting effects of ESI on social reward processing and molecular pathways, providing insight into differential susceptibility to social adversity.
