Multidimensional Effects of Stress on Neuronal Exosome Levels and Simultaneous Transcriptomic Profiles

Area of Science:

• Neurobiology
• Cellular Biology
• Molecular Biology

Background:

• Exosomes, nanovesicles regulating brain plasticity, are potential therapeutic targets for stress-related mental illnesses.
• The impact of chronic stress on exosome levels and their molecular drivers remains largely unknown.

Purpose of the Study:

• To investigate the effects of chronic restraint stress (CRS) on neuronal exosome levels in specific brain regions and plasma of male mice.
• To identify molecular factors influencing exosome levels during the stress response.

Main Methods:

• Isolation of neuronal exosomes from mouse plasma, ventral dentate gyrus, basolateral amygdala, and olfactory bulbs using complementary strategies.
• RNA sequencing and bioinformatic analyses to identify molecular drivers of exosome levels.

Main Results:

• CRS increased neuronal exosome levels in plasma and ventral dentate gyrus, but decreased them in the basolateral amygdala, showing regional specificity.
• Acetyl-L-carnitine administration normalized CRS-induced increases in plasma neuronal exosome levels.
• CRS-induced exosome level changes in the brain mirrored inverse transcriptional changes, with beta-estradiol signaling implicated as a potential driver.

Conclusions:

• Demonstrates specific relationships between neuronal exosome levels in plasma and the brain under chronic stress.
• Identifies potential therapeutic targets for normalizing exosome levels in stress-related disorders.
• Establishes a foundation for understanding local and distant communication in stress neurobiology via exosomes.