ArticleScientific reports2019
Ancestral Stress Alters Lifetime Mental Health Trajectories and Cortical Neuromorphology via Epigenetic Regulation.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- Prenatal maternal stress in rats alters the epigenetic and transcriptomic landscape of the maternal-fetal interface across four generations.Communications biology · 2025Article
- Sex-dependent biobehavioural responses to transgenerational maternal stress: evidence of stress resilience and vulnerability in the F3 generation.Environmental epigenetics · 2025Article
- Prenatal maternal life adversity impacts on learning and memory in offspring: implication to transgenerational epigenetic inheritance.Frontiers in neuroscience · 2025Article
- Grandfathers-to-Grandsons Transgenerational Transmission of Exercise Positive Effects on Cognitive Performance.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Early life stress shifts critical periods and causes precocious visual cortex development.PloS one · 2024Article
- Thermoregulatory dynamics reveal sex-specific inflammatory responses to experimental autoimmune encephalomyelitis in mice: Implications for multiple sclerosis-induced fatigue in females.Brain, behavior, & immunity - health · 2022Article
- Trans- and Multigenerational Maternal Social Isolation Stress Programs the Blood Plasma Metabolome in the F3 Generation.Metabolites · 2022Article
- Social Isolation Stress Modulates Pregnancy Outcomes and the Inflammatory Profile of Rat Uterus.International journal of molecular sciences · 2022Article
- Epigenetic Approach to PTSD: In the Aspects of Rat Models.Global medical genetics · 2022Review
- Sex-specific stress and biobehavioral responses to human experimenters in rats.Frontiers in neuroscience · 2022Article
- Developmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk.International journal of molecular sciences · 2021Review
- Aging, Social Distancing, and COVID-19 Risk: Who is more Vulnerable and Why?Aging and disease · 2021Review
- Article
- Generalized and social anxiety disorder interactomes show distinctive overlaps with striosome and matrix interactomes.Scientific reports · 2021Article
- The role of epigenetics in psychological resilience.The lancet. Psychiatry · 2021Review
- The stressed orbitofrontal cortex.Behavioral neuroscience · 2021Article
- Ancestral stress programs sex-specific biological aging trajectories and non-communicable disease risk.Aging · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Experiences during early development are powerful determinants of lifetime mental health. Here we investigated if ancestral stress regulates the brain's epigenetic memory to alter neuromorphology and emotionality in the remote F4 progeny. Pregnant female rat dams of the parental F0 generation were exposed to stress on gestational days 12-18. To generate a transgenerational stress lineage, their pregnant daughters (F1), grand-daughters (F2) and great-grand-daughters (F3) remained undisturbed. To generate a multigenerational stress lineage, pregnant dams of each generation (F1-F3) were stressed. A lineage of non-stress controls (F0-F3) was also produced. Multigenerational stress exceeded the impact of transgenerational stress by increasing anxiety-like behaviours and stress response in young and middle-aged F4 males but not females. Functional changes were accompanied by reduced spine density in the male medial prefrontal cortex with opposite effects in the orbital frontal cortex. Ancestral stress regulated cortical miR-221 and miR-26 expression and their target genes, thus downregulating ntrk2 and map1a genes in males while downregulating crh and upregulating map1a genes in females. These miRNA-dependent pathways are candidates for developmental programming of lifetime mental health. Thus, multigenerational stress in particular determines sexually dimorphic predisposition to stress vulnerability and generates a phenotype resembling symptoms of post-traumatic stress disorder.
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