L1CAM extracellular vesicles derived from the serum of adolescents with major depressive disorder induce depression-like phenotypes in adolescent mice.

BACKGROUND

It has been reported that L1 cell adhesion molecule (L1CAM) antibody can capture neuron-derived extracellular vesicles (NDEVs) derived from peripheral blood. This antibody is significantly associated with occurrence of adult psychiatric disorders. However, the role and mechanism of L1CAM EVs (L1 EVs) in adolescent with major depressive disorder (AMDD) is not well understood. This research aimed to explore the function and potential mechanism of L1 EVs and miRNAs genes in AMDD.

METHODS

L1 EVs derived from the serum of AMDD and healthy controls (HC) were transplanted into adolescent mice via tail vein. Their effects were explored using behavioral tests, hippocampal Nissl staining, and whole genome mRNA sequencing. MiRNAs expression in L1 EVs was evaluated by whole-genome sequencing and qRT-PCR. Bioinformatics analysis was employed to explore the possible pathogenic molecular mechanisms of these miRNAs in AMDD.

RESULTS

Transplantation of L1 EVs from AMDD induced depression-like behavior and hippocampal neuronal damage in adolescent mice and aberrant expression of 298 mRNA genes. The molecular signals related to MDD were enriched in the top pathways of the differentially expressed genes. Compared with HC, miR-375-3p and miR-200a-3p were upregulated in L1 EVs from AMDD, miR-375-3p was also increased in the hippocampus of AMDD serum L1 EVs-recipient mice. Bioinformatics analysis revealed that miR-375-3p might modulate the network of molecules associated with the MAPK pathway via protein interaction involving hippocampal differential genes Cadm2, Cacna2d1, and Casz1.

CONCLUSION

MiR-375-3p might contribute to L1 EVs-induced AMDD. L1 EVs miR-375-3p and miR-200a-3p could potentially serve as potential biomarkers for AMDD.