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Updated: Oct 3, 2025
Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
Evidence for Effects of Extracellular Vesicles on Physical, Inflammatory, Transcriptome and Reward Behaviour Status
Nagiua Cuomo-Haymour1,2, Hannes Sigrist1, Christian Ineichen1
1Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics Psychiatric Hospital, University of Zurich, 8008 Zurich, Switzerland.
Abstract:
Immune-inflammatory activation impacts extracellular vesicles (EVs), including their miRNA cargo. There is evidence for changes in the EV miRNome in inflammation-associated neuropsychiatric disorders. This mouse study investigated: (1) effects of systemic lipopolysaccharide (LPS) and chronic social stress (CSS) on plasma EV miRNome; and (2) physiological, transcriptional, and behavioural effects of peripheral or central delivered LPS-activated EVs in recipient mice. LPS or CSS effects on the plasma EV miRNome were assessed by using microRNA sequencing. Recipient mice received plasma EVs isolated from LPS-treated or SAL-treated donor mice or vehicle only, either intravenously or into the nucleus accumbens (NAc), on three consecutive days. Bodyweight, spleen or NAc transcriptome and reward (sucrose) motivation were assessed. LPS and CSS increased the expression of 122 and decreased expression of 20 plasma EV miRNAs, respectively. Peripheral LPS-EVs reduced bodyweight, and both LPS-EVs and SAL-EVs increased spleen expression of immune-relevant genes. NAc-infused LPS-EVs increased the expression of 10 immune-inflammatory genes. Whereas motivation increased similarly across test days in all groups, the effect of test days was more pronounced in mice that received peripheral or central LPS-EVs compared with other groups. This study provides causal evidence that increased EV levels impact physiological and behavioural processes and are of potential relevance to neuropsychiatric disorders.
Insights
Systemic inflammation alters extracellular vesicle (EV) microRNAs. Activated EVs influenced physiological and behavioral outcomes in mice, suggesting a role in neuropsychiatric disorders.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Immune-inflammatory responses can alter extracellular vesicles (EVs) and their microRNA (miRNA) content.
- Dysregulation of the EV miRNome is implicated in inflammation-associated neuropsychiatric disorders.
Purpose of the Study:
- To investigate the impact of systemic lipopolysaccharide (LPS) and chronic social stress (CSS) on the plasma EV miRNome in mice.
- To determine the physiological, transcriptional, and behavioral effects of LPS-activated EVs delivered peripherally or centrally in recipient mice.
Main Methods:
- MicroRNA sequencing was used to analyze plasma EV miRNomes after LPS or CSS exposure.
- Recipient mice received plasma EVs intravenously or into the nucleus accumbens (NAc) from LPS-treated or saline-treated donors.
- Assessed outcomes included body weight, spleen and NAc transcriptome, and sucrose reward motivation.
Main Results:
- LPS and CSS significantly altered plasma EV miRNA expression, with 122 miRNAs upregulated and 20 downregulated by LPS.
- Peripheral LPS-EV administration reduced body weight; both LPS-EVs and saline-EVs increased immune-related gene expression in the spleen.
- Central LPS-EV infusion upregulated immune-inflammatory genes in the NAc, and peripheral/central LPS-EVs enhanced the effect of test days on motivation.
Conclusions:
- Systemic inflammation and stress modify the plasma EV miRNome.
- EVs derived from inflamed states can causally influence physiological and behavioral processes.
- These findings highlight the potential relevance of EV alterations in the pathophysiology of neuropsychiatric disorders.
