GABAergic MicroRNA-34a in the Dorsal Raphe Nuclei Contributes to Circulating MicroRNA-34a Levels.

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Brain microRNAs (miRs) are cell-specific and linked to pathologies.
• Circulating miRs (c-miRs) show potential as biomarkers for brain disorders.
• The dorsal raphe nuclei (DRN) express mir-34a in GABAergic neurons, increasing with stress or SSRI treatment.

Purpose of the Study:

• To determine if plasma miR-34a levels indicate its expression in the DRN.
• To identify the source of plasma miR-34a.
• To explore the pathway of miR-34a from brain to periphery.

Main Methods:

• Mice were subjected to repeated social defeat stress or chronic SSRI administration.
• Genetic deletion of miR-34a in GABAergic neurons was performed.
• AntagomiR-34a was infused into the DRN.

Main Results:

• Plasma miR-34a levels increased significantly following stress or SSRI administration.
• Selective deletion of miR-34a in DRN GABAergic neurons reduced plasma miR-34a.
• DRN infusion of AntagomiR-34a reduced plasma miR-34a and choroid plexus miR-34a.

Conclusions:

• Plasma miR-34a serves as a peripheral indicator of miR-34a expression in DRN GABAergic neurons.
• DRN GABAergic neurons are the primary source of plasma miR-34a.
• c-miRs can report homeostatic adaptations in specific neuronal populations.