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Morphine reprograms brain-derived extracellular vesicle cargo associated with synaptic remodeling in the prefrontal
Pedro H Gobira1, Savio Bastos1, Rachele Rossi2
1Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Neurobiology of Disease
|June 24, 2026
Summary
Brain-derived extracellular vesicles (BDEVs) from morphine-exposed rats carry molecular signals. These BDEVs alter gene expression in healthy neurons, suggesting a role in opioid-induced brain changes.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Extracellular vesicles (EVs) are crucial for intercellular communication in the brain.
- Chronic opioid exposure causes significant neuroadaptations, but the role of brain-derived EVs (BDEVs) is unclear.
Purpose of the Study:
- To investigate the cargo of BDEVs from rats chronically exposed to morphine.
- To determine if morphine-induced BDEVs influence neuronal function.
Main Methods:
- Isolation of BDEVs from the prefrontal cortex of morphine-treated rats.
- Integrated transcriptomic and proteomic analysis of BDEV cargo.
- Treatment of naïve cortical neurons with BDEVs to assess functional effects.
Main Results:
- Morphine-associated BDEVs showed altered pathways related to synaptic plasticity, ER stress, mitochondrial function, and neurodegeneration.
- Increased mRNA for the synaptic regulator Arc and upregulation of ER stress marker Hspa5 were observed.
- Morphine-derived BDEVs induced changes in gene expression related to synaptic remodeling and excitability in recipient neurons.
Conclusions:
- BDEVs play a role in mediating intercellular communication during chronic opioid exposure.
- BDEV cargo reflects neuroadaptive changes induced by morphine.
- BDEVs may contribute to the development of opioid-induced neuroadaptations.
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