Genomic and epigenomic responses to chronic stress involve miRNA-mediated programming

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Stress significantly impacts motor system function and movement performance.
• Brain-specific changes in microRNA (miRNA) and gene expression are hypothesized to underlie stress-induced motor impairments.

Purpose of the Study:

• To investigate the causal link between stress, motor impairment, and genetic/epigenetic changes in central motor areas.
• To identify specific genes and miRNAs affected by stress in the rat brain.

Main Methods:

• Exposure of rats to two weeks of mild restraint stress.
• Analysis of gene and miRNA expression in the cerebellum, hippocampus, and prefrontal cortex.
• Identification of miRNA targets.

Main Results:

• Mild stress altered the expression of 39 genes and 9 miRNAs in the cerebellum.
• Some expression changes persisted after stress recovery, correlating with behavioral impairments.
• Stress modulated Adipoq and prolactin receptor (Prlr) mRNA in the cerebellum, and Prlr, miR-186, and miR-709 in the hippocampus and prefrontal cortex.
• miR-186 was identified as a target of the Eps15 gene.
• Age-dependent increases in EphrinB3 and GabaA4 receptors were observed.

Conclusions:

• Even mild stress induces significant genomic and epigenomic alterations in the motor system, including changes in miRNA expression.
• miRNA-regulated gene expression plays a central role in the physiological stress response and associated neurological functions.
• These findings provide insights into the molecular mechanisms underlying stress-related motor deficits.