ArticleBMC genomics2021
Early life and adult stress promote sex dependent changes in hypothalamic miRNAs and environmental enrichment prevents stress-induced miRNA and gene expression changes in rats.
Article in BMC genomics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.
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Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Recent developments in omics studies and artificial intelligence in depression and suicide.Translational psychiatry · 2025Pooled it
- Can Environmental Enrichment Modulate Epigenetic Processes in the Central Nervous System Under Adverse Environmental Conditions? A Systematic Review.Cellular and molecular neurobiology · 2024Pooled it
- Environmental enrichment as an intervention to prevent behavioral and neurobiological consequences of maternal separation in rodents: a scope review.Neurobiology of stress · 2026Article
- Spatially resolved molecular sex differences at single-cell resolution in the adult human ventromedial and arcuate hypothalamus.Cell reports · 2026Article
- Silent regulators of trauma: the microRNA blueprint underlying post-traumatic stress disorder biology.Environmental epigenetics · 2026Review
- Stress-Associated Changes in MiR-20b-3p as a Potential Predictor of Underlying Psychopathology in the Depressed Brain: Mechanistic Insights from a Rat Model of Chronic Restraint Stress.Molecular neurobiology · 2025Article
- Profiling fear-extinction learning induced small ncRNAs landscape and identifying miR-29b-3p as a promising biomarker for PTSD.Journal of translational medicine · 2025Article
- Epitranscriptomic shifts in M6A RNA methylation influencing transcriptional dynamics in the prefrontal cortex of chronic restraint stress rats.Neurochemistry international · 2025Article
- Genetic, Epigenetic, and Hormonal Regulation of Stress Phenotypes in Major Depressive Disorder: From Maladaptation to Resilience.Cellular and molecular neurobiology · 2025Review
- Environmental enrichment with nylon gnaw sticks introduces variation in Sprague Dawley rat immune and lower gastrointestinal parameters with differences between sexes.Animal microbiome · 2025Article
- Epigenetic Modifications and Neuroplasticity in the Pathogenesis of Depression: A Focus on Early Life Stress.Behavioral sciences (Basel, Switzerland) · 2024Review
- Acute restraint stress regulates brain DNMT3a and promotes defensive behaviors in male rats.Neuroscience letters · 2024Article
- A bibliometric analysis of studies on environmental enrichment spanning 1967-2024: patterns and trends over the years.Frontiers in behavioral neuroscience · 2024Article
- Endocannabinoid signaling and epigenetics modifications in the neurobiology of stress-related disorders.Neuronal signaling · 2023Review
- An insight into the sprawling microverse of microRNAs in depression pathophysiology and treatment response.Neuroscience and biobehavioral reviews · 2023Review
- Oral Delivery of miR-320-3p with Lipidic Aminoglycoside Derivatives at Mid-Lactation Alters miR-320-3p Endogenous Levels in the Gut and Brain of Adult Rats According to Early or Regular Weaning.International journal of molecular sciences · 2022Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe hypothalamus plays a key role in the stress response. While early life stress (ELS) increases susceptibility to psychiatric disorders including major depressive disorder (MDD), acute stress during adulthood can also precipitate MDD after ELS.
aimHere, we tested the expression of miRNAs following ELS and susceptibility to depression-like behavior and whether sex or acute stress exacerbates this response. We also tested whether environmental enrichment (Enr) promotes early life and adult behavioral stress resilience and its effect on hypothalamic miRNA and gene expression. Following rat maternal separation (MS) as an ELS model, Enr from weaning through adulthood, and restraint (RS) as acute adult stress, we tested both animal behavior and miRNA expression in the hypothalamus. Target genes and their enrichment and ontology were analyzed using bioinformatic tools. Target gene expression changes were tested using qPCR, and miRNA promoter methylation was studied using methylated-DNA immunoprecipitation qPCR.
resultsMS, Enr, RS, and sex altered hypothalamic miRNAs, including several previously reported in MS literature: miRs-29, - 124, - 132, - 144, - 504. Sex had a significant effect on the greatest number of miRNAs. Also, Enr reversed downregulation of miR-29b-1-5p and -301b-3p in MS. qPCR showed that MAPK6 and MMP19, targets of miR-301b-3p, were upregulated in MS and reversed by Enr. Additionally, miR-219a was hypermethylated in MS coinciding with decreased miR-219a expression.
conclusionsThis study found that sex plays a critical role in the hypothalamic miRNA response to both ELS and acute stress, with males expressing greater changes following postnatal stress. Moreover, enrichment significantly altered behavior as well as hypothalamic miRNA expression and their gene targets. Because of its role as the initiator of the autonomic stress response and connection to hedonic and motivational behavior, the hypothalamic miRNA landscape may significantly alter both the short and long-term behavioral response to stress.
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