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A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
Published on: May 15, 2019
Young plasma administration mitigates depression-like behaviours in chronic mild stress-exposed aged rats by
Arshad Ghaffari-Nasab1, Reza Badalzadeh1,2, Gisou Mohaddes1
1Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Insights
Repeated young plasma transfusions improved depressive behaviors in aged rats by reducing prefrontal cortex apoptosis. This suggests young plasma may counteract age-related depression and neurodegeneration.
Area of Science:
- Neuroscience
- Gerontology
- Molecular Biology
Background:
- Brain aging impacts stress response and contributes to late-life depression pathophysiology.
- Increased apoptotic activity in the prefrontal cortex is observed in aging and stress-related mood disorders.
- Young blood factors show potential in reversing age-related organ dysfunction, particularly in the brain.
Purpose of the Study:
- To investigate the effect of young plasma administration on depressive behaviors in aged rats.
- To examine the impact of young plasma on apoptosis in the prefrontal cortex of aged rats subjected to chronic unpredictable mild stress (CUMS).
Main Methods:
- Aged rats were subjected to CUMS to model depression.
- The experimental group received young plasma transfusions (1 ml, IV, 3x/week for 4 weeks).
- Depressive behaviors were assessed, and prefrontal cortex apoptosis was analyzed (TUNEL assay, cleaved caspase-3 levels).
Main Results:
- Young plasma transfusion significantly improved CUMS-induced depression-like behaviors in aged rats.
- This improvement was associated with a reduction in neuronal apoptosis in the prefrontal cortex.
- Reduced TUNEL-positive cells and cleaved caspase-3 protein levels were observed in the young plasma-treated group.
Conclusions:
- Repeated young plasma transfusion can ameliorate depressive behaviors in aged rats.
- Young plasma exerts neuroprotective effects by reducing apoptosis in the prefrontal cortex.
- These findings suggest young plasma may offer a therapeutic strategy for late-life depression by targeting apoptotic signaling pathways.
New Findings:
What is the central question of this study? Young plasma contains several rejuvenating factors that exert beneficial effects in ageing and neurodegenerative diseases: can repeated transfusion of young plasma improve depressive behaviour in aged rats? What is the main finding and its importance? Following chronic transfusion of young plasma, depressive behaviour was improved in the depression model of aged rats, which was associated with reduced apoptosis process in the prefrontal cortex.
Abstract:
Brain ageing alters brain responses to stress, playing an essential role in the pathophysiology of late-life depression. Moreover, apoptotic activity is up-regulated in the prefrontal cortex in ageing and stress-related mood disorders. Considerable evidence suggests that factors in young blood could reverse age-related dysfunctions in organs, especially in the brain. Therefore, this study investigated the effect of young plasma administration on depressive behaviours in aged rats exposed to chronic unpredictable mild stress (CUMS), with a focus on the apoptosis process. Young (3 months old) and aged (22 months old) male rats were randomly assigned into four groups: young control (YC), aged control (AC), aged rats subjected to CUMS (A+CUMS) and aged rats subjected to CUMS and treated with young plasma (A+CUMS+YP). In the A+CUMS and A+CUMS+YP groups, CUMS was used to generate the depression rat model. Moreover, the A+CUMS+YP group received pooled plasma (1 ml, intravenously), collected from young rats, three times per week for 4 weeks. Young plasma administration significantly improved CUMS-induced depression-like behaviours, including decreased sucrose consumption ratio, reduced locomotor activity and prolonged immobility time. Importantly, young plasma reduced neuronal apoptosis in the prefrontal cortex that was associated with reduced TUNEL-positive cells and cleaved caspase-3 protein levels in the A+CUMS+YP compared with the A+CUMS group. Young plasma can partially improve the neuropathology of late-life depression through the apoptotic signalling pathways.

