ArticlePloS one2015
Prenatal stress down-regulates Reelin expression by methylation of its promoter and induces adult behavioral impairments in rats.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06876051 (The Impact of Prenatal Stress Management Program on Maternal Breastfeeding and Neonatal Neurodevelopmental Parameters), which is not on this map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Impact of Prenatal Stress Management Program on Maternal Breastfeeding and Neonatal Neurodevelopmental Parameters
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Reelin Alterations, Behavioral Phenotypes, and Brain Anomalies in Schizophrenia: A Systematic Review of Insights From Rodent Models.Frontiers in neuroanatomy · 2022Pooled it
- Early Life Stress and Adversity in Children: Neuroendocrine Mechanisms, Epigenetic Regulation, and Lifespan Developmental Outcomes-A Narrative Review.Children (Basel, Switzerland) · 2026Review
- The Convergence of Early-Life Stress and Autism Spectrum Disorder on the Epigenetics of Genes Key to the HPA Axis.Biology · 2025Review
- Investigating the impact of severe maternal SARS-CoV-2 infection on infant DNA methylation and neurodevelopment.Molecular psychiatry · 2025Article
- The Psychoneuroimmunological Model of Moral Distress and Health in Healthcare Workers: Toward Individual and System-Level Solutions.Comprehensive psychoneuroendocrinology · 2024Review
- Article
- Prenatal Stress Induces Long-Term Behavioral Sex-Dependent Changes in Rats Offspring: the Role of the HPA Axis and Epigenetics.Molecular neurobiology · 2023Article
- DNA Methylation in Depression and Depressive-Like Phenotype: Biomarker or Target of Pharmacological Intervention?Current neuropharmacology · 2022Review
- Epigenetic mechanisms impacted by chronic stress across the rodent lifespan.Neurobiology of stress · 2022Article
- The Role of MeCP2 in Regulating Synaptic Plasticity in the Context of Stress and Depression.Cells · 2022Review
- Molecular actions of sex hormones in the brain and their potential treatment use in anxiety disorders.Frontiers in psychiatry · 2022Review
- A comprehensive approach to modeling maternal immune activation in rodents.Frontiers in neuroscience · 2022Review
- A novel murine model to study the impact of maternal depression and antidepressant treatment on biobehavioral functions in the offspring.Molecular psychiatry · 2021Article
- Prenatal stress effects on offspring brain and behavior: Mediators, alterations and dysregulated epigenetic mechanisms.Journal of biosciences · 2021Review
- Role of DNA Methylation in Mediating Genetic Risk of Psychiatric Disorders.Frontiers in psychiatry · 2021Review
- Maternal Distress and Offspring Neurodevelopment: Challenges and Opportunities for Pre-clinical Research Models.Frontiers in human neuroscience · 2021Article
- Prenatal stress enhances NNK-induced lung tumors in A/J mice.Carcinogenesis · 2020Article
- Influence of prenatal transportation stress-induced differential DNA methylation on the physiological control of behavior and stress response in suckling Brahman bull calves.Journal of animal science · 2020Article
- Reelin Supplementation Into the Hippocampus Rescues Abnormal Behavior in a Mouse Model of Neurodevelopmental Disorders.Frontiers in cellular neuroscience · 2020Article
- Epigenome-wide association study of depression symptomatology in elderly monozygotic twins.Translational psychiatry · 2019Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Prenatal stress causes predisposition to cognitive and emotional disturbances and is a risk factor towards the development of neuropsychiatric conditions like depression, bipolar disorders and schizophrenia. The extracellular protein Reelin, expressed by Cajal-Retzius cells during cortical development, plays critical roles on cortical lamination and synaptic maturation, and its deregulation has been associated with maladaptive conditions. In the present study, we address the effect of prenatal restraint stress (PNS) upon Reelin expression and signaling in pregnant rats during the last 10 days of pregnancy. Animals from one group, including control and PNS exposed fetuses, were sacrificed and analyzed using immunohistochemical, biochemical, cell biology and molecular biology approaches. We scored changes in the expression of Reelin, its signaling pathway and in the methylation of its promoter. A second group included control and PNS exposed animals maintained until young adulthood for behavioral studies. Using the optical dissector, we show decreased numbers of Reelin-positive neurons in cortical layer I of PNS exposed animals. In addition, neurons from PNS exposed animals display decreased Reelin expression that is paralleled by changes in components of the Reelin-signaling cascade, both in vivo and in vitro. Furthermore, PNS induced changes in the DNA methylation levels of the Reelin promoter in culture and in histological samples. PNS adult rats display excessive spontaneous locomotor activity, high anxiety levels and problems of learning and memory consolidation. No significant visuo-spatial memory impairment was detected on the Morris water maze. These results highlight the effects of prenatal stress on the Cajal-Retzius neuronal population, and the persistence of behavioral consequences using this treatment in adults, thereby supporting a relevant role of PNS in the genesis of neuropsychiatric diseases. We also propose an in vitro model that can yield new insights on the molecular mechanisms behind the effects of prenatal stress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.