Related Experiment Video
Updated: Sep 16, 2025
Chronic Social Defeat Stress in Early Adolescent Male Mice
Published on: January 24, 2025
Oxytocin Intervention Mitigates Pathological and Behavioral Impairments in APP/PS1 Mice Subjected to Early Social
Junjun Li1, Yue Li1, Zhuoya Wang1
1Department of Neurosurgery, Sichuan Provincial People's Hospital, MOE Key Lab for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
Background:
Neuropsychiatric symptoms, such as anxiety and depression, are prevalent during the prodromal phase of Alzheimer's disease (AD). Social isolation (SI) has been implicated as a potential exacerbating factor for emotional disturbances in AD pathogenesis. Despite the well-established role of oxytocin (OXT) in regulating social behavior and mental health, its function and mechanisms in alleviating AD-related psychiatric symptoms remain poorly understood.
Materials And Methods:
We utilized a 12-week SI model to assess its effects on anxiety, depression-like behaviors, and social cognition in early-stage AD mice. Through immunofluorescence, enzyme-linked immunosorbent assay, and 16S rDNA sequencing, we examined the changes in AD pathology and gut microbiota composition induced by SI, as well as the effects of OXT intervention.
Results:
Our findings revealed that SI markedly intensified anxiety-like behaviors, depression-like phenotypes, and social cognitive impairments in AD mice. Mechanistically, SI resulted in decreased OXT levels and upregulated OXT receptor expression while also exacerbating AD-related pathological features, including increased Aβ plaque deposition, aberrant microglial proliferation, and reduced PSD-95 expression in the prefrontal cortex. Furthermore, SI induced significant changes in gut microbiota composition. OXT intervention demonstrated therapeutic efficacy by mitigating behavioral deficits, alleviating AD-related pathological damage, and restoring gut microbiota homeostasis in SI AD mice.
Conclusion:
These results underscore OXT as a promising therapeutic avenue for AD, offering novel insights into treatment strategies and identifying potential therapeutic targets through the restoration of gut homeostasis and mitigation of pathological processes.
