MicroRNA Regulates Early-Life Stress–Induced Depressive Behavior via Serotonin Signaling in a Sex-Dependent Manner in the Prefrontal Cortex of Rats
Year: 2021
Type: article
Abstract: The underlying neurobiology of early-life stress (ELS)-induced major depressive disorder is not clearly understood. In this study, we used maternal separation (MS) as a rodent model of ELS and tested whether microRNAs (miRNAs) target serotonin genes to regulate ELS-induced depression-like behavior and whether this effect is sex dependent. We also examined whether environmental enrichment prevents susceptibility to depression- and anxiety-like behavior following MS and whether enrichment effects are mediated through serotonin genes and their corresponding miRNAs. MS decreased sucrose preference, which was reversed by enrichment. Males also exhibited greater changes in forced swim climbing and escape latency tests only following enrichment. Slc6a4 and Htr1a were upregulated in the frontal cortex following MS. In male MS rats, enrichment slightly reversed Htr1a expression to levels similar to control rats. miR-200a-3p and miR-322-5p, which target SLC6A4, were decreased by MS, but not significantly. An HTR1A-targeting miRNA, miR-320-5p, was also downregulated by MS and showed slight reversal by enrichment in male animals. miR-320-5p targeting of Htr1a was validated in vitro using SHSY neuroblastoma cell lines. Altogether, this study implicates miRNA interaction with the serotonin pathway in ELS-induced susceptibility to depression-related reward deficits. Furthermore, because of its recovery by enrichment in males, miR-320 may represent a viable sex-specific target for reward-related deficits in major depressive disorder.
Authors: Lauren Allen McKibben, Yogesh Dwivedi
Institution: University of Alabama at Birmingham
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,200
Awards: G1016622791, G1478726521, Epitranscriptomic Mapping of Novel N6-Adenosine-based RNA Methylation in MDD Brain, G1796580632, G1866546576, G3465161316, Perturbed cell signaling network and suicide neurobiology, MicroRNA Mediators of Early Life Stress Vulnerability and Resilience, G4711164991, Calcium Sensing Proteins in Depression, G5163787543, G5343995942, MicroRNA Mapping in Major Depression, G6280069923, G672510336, G7412532641, G7512622950, G809423026, G832260, G8791425458
OpenAlex ID: W3172267883