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Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
BV2-derived extracellular vesicles modulate microglia inflammatory profile, neuronal plasticity, and behavioural
Arianna Rinaldi1, Marta Balietti2, Elisa Principi3
1Department of Physiology and Pharmacology, Sapienza University, Rome, Italy.
Background:
During aging, both the brain and the immune system undergo a progressive impairment of physiological functions. Microglia, the immunocompetent cells of the central nervous system, shift towards a chronic mild inflammatory state that impacts brain homeostasis. Extracellular vesicles (EVs) released by microglia transport packages of molecular information that mirror the inflammatory status of donor cells and modulate the inflammatory phenotype of recipient microglia and other cell types.
Results:
We demonstrated that intranasal administration of EVs derived from microglial-like BV2 cells to late adult mice (16-20 months of age) shifts microglia toward a "juvenile" morphology affecting their inflammatory profile. Mice treated with BV2-derived EVs have a reduction of anxiety-like behavior and an increased spatial learning, with sex-dependent differences. Further, BV2-derived EVs increased neuronal plasticity both in male and female mice. These findings suggest the involvement of microglial cells in vesicles-mediated anti-aging effect.
Conclusions:
Our data indicate that BV2-derived EVs could represent a resource to slow down age-dependent inflammation in the mouse brain.
Insights
Microglia-derived extracellular vesicles (EVs) can rejuvenate aging brains. Treatment with these EVs reduced inflammation, anxiety, and improved learning and neuronal plasticity in aged mice.
Area of Science:
- Neuroscience
- Immunology
- Aging Research
Background:
- Aging impairs brain and immune functions, leading to chronic inflammation.
- Microglia, the brain's immune cells, become chronically inflamed, disrupting homeostasis.
- Microglia-released extracellular vesicles (EVs) carry molecular signals influencing cell inflammation.
Purpose of the Study:
- To investigate the potential of microglial extracellular vesicles (EVs) in mitigating age-related brain changes.
- To assess the impact of BV2 cell-derived EVs on microglia and cognitive functions in aged mice.
Main Methods:
- Intranasal administration of extracellular vesicles (EVs) derived from microglial-like BV2 cells to aged mice (16-20 months).
- Evaluation of microglial morphology and inflammatory profiles.
- Assessment of anxiety-like behavior, spatial learning, and neuronal plasticity.
Main Results:
- BV2-derived EVs induced a shift towards a "juvenile" microglial morphology and altered inflammatory profiles.
- EV treatment reduced anxiety-like behaviors and enhanced spatial learning in aged mice, with sex-specific effects.
- Increased neuronal plasticity was observed in both male and female mice following EV administration.
Conclusions:
- Microglia-derived EVs show potential in counteracting age-dependent brain inflammation.
- BV2-derived EVs may serve as a therapeutic resource to slow brain aging processes.
