Exosomal miR-24-3p participates in the progression of depression by regulating neuronal damage and blood-brain barrier dysfunction.

Abstract

Background: The blood-brain barrier (BBB) is essential for maintaining normal brain function and is involved in the progression of major depressive disorder (MDD). This study investigated the abnormal expression and regulatory role of miR-24-3p in neuronal injury and BBB dysfunction during MDD pathogenesis.

Methods: The expression of miR-24-3p was examined in serum samples from patients with MDD and from chronic unpredictable mild stress and lipopolysaccharide mouse models, as well as in hippocampal tissue from mice. A loss-of-function assay was conducted to explore the role of miR-24-3p in brain injury, assessing neuronal cell viability, apoptosis, inflammatory response, oxidative stress, and astrocyte activation. Exosomes were then isolated to evaluate the regulatory role and function of miR-24-3p in BBB dysfunction. Behavioural tests were performed to assess depressive-like behaviours in mice.

Results: miR-24-3p was significantly upregulated in MDD samples. Inhibiting miR-24-3p suppressed LPS-induced neuronal apoptosis and inflammation, while promoting the secretion of neurofunctional factors. Further analysis revealed that inhibiting exosomal miR-24-3p alleviated depressive-like behaviour in MDD model mice, reduced BBB permeability, and improved BBB function.

Conclusion: miR-24-3p inhibition attenuated neuronal damage, reduced astrocyte activation, and enhanced BBB stability through exosome-mediated regulation, thereby alleviating neurobehavioural abnormalities and the progression of MDD.