ArticleHormones and behavior2024
Thyroid hormones mediate the impact of early-life stress on ventral tegmental area gene expression and behavior.
Article in Hormones and behavior, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 25 citations in OpenAlex.
- Altered Postnatal Chromatin Development in the Nucleus Accumbens Primes Enduring Stress Sensitivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
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- Male and female mice are similarly susceptible to chronic nondiscriminatory social defeat stress despite differences in attack frequency from aggressor.Psychopharmacology · 2026Article
- Differential Methylation by Early Life Adversity in the Future of Families Child Wellbeing Study.bioRxiv : the preprint server for biology · 2026Article
- Iridophore apoptosis mediates socially-regulated developmental color pattern plasticity in an anemonefish.PLoS biology · 2026Article
- Epigenetic regulation of brain development, plasticity, and response to early-life stress.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Neurobiology of resilience to early life stress.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Negr1 Deficiency Modulates Sex-Specific Neurobehavioral Adaptations to Social Isolation.Brain sciences · 2025Article
- Altered postnatal chromatin development in the nucleus accumbens primes lifelong stress sensitivity.bioRxiv : the preprint server for biology · 2025Article
- Central thyroid hormone receptor-beta: Sensitivity to alcohol and a role in regulating alcohol drinking.Hormones and behavior · 2025Article
- Persistent open chromatin state in early-life stress-activated cells of the VTA.Scientific reports · 2025Article
- Early-life stress sensitizes response to future stress: Evidence and mechanisms.Neurobiology of stress · 2025Review
- Molecular heterogeneity and development of the ventral tegmental area.Current opinion in behavioral sciences · 2025Article
- Recent Insights on the Role of Nuclear Receptors in Alzheimer's Disease: Mechanisms and Therapeutic Application.International journal of molecular sciences · 2025Review
- Impact of Psychological Stress-Derived Hormones and Cytokines on Immune Cell Profiles in Vitiligo: Toward Improved Peripheral Blood Simulation in Animal Models.Clinical, cosmetic and investigational dermatology · 2025Review
- Enduring memory consequences of early-life stress / adversity: Structural, synaptic, molecular and epigenetic mechanisms.Neurobiology of stress · 2024Review
- Limited Bedding and Nesting as a Model for Early-Life Adversity in Mice.Journal of visualized experiments : JoVE · 2024Article
- Longevity, demographic characteristics, and socio-economic status are linked to triiodothyronine levels in the general population.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Brain alterations in adolescents with first-episode depression who have experienced adverse events: evidence from resting-state functional magnetic resonance imaging.Frontiers in psychiatry · 2024Article
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5 authors at 1 institution in 1 country.
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Abstract
Proper thyroid function is essential to the developing brain, including dopamine neuron differentiation, growth, and maintenance. Stress across the lifespan impacts thyroid hormone signaling and anxiety disorders and depression have been associated with thyroid dysfunction (both hypo- and hyper-active). However, less is known about how stress during postnatal development impacts thyroid function and related brain development. Our previous work in mice demonstrated that early-life stress (ELS) transiently impinged on expression of a transcription factor in dopamine neurons, Otx2, shown to be regulated by thyroid hormones. We hypothesized that thyroid hormone signaling may link experience of ELS with transcriptional dysregulation within the dopaminergic midbrain, and ultimately behavior. Here, we find that ELS transiently increases thyroid-stimulating hormone levels (inversely related to thyroid signaling) in both male and female mice at P21, an effect which recovers by adolescence. We next tested whether transient treatment of ELS mice with synthetic thyroid hormone (levothyroxine, LT4) could ameliorate the impact of ELS on sensitivity to future stress, and on expression of genes related to dopamine neuron development and maintenance, thyroid signaling, and plasticity within the ventral tegmental area. Among male mice, but not females, juvenile LT4 treatment prevented hypersensitivity to adult stress. We also found that rescuing developmental deficits in thyroid hormone signaling after ELS restored levels of some genes altered directly by ELS, and prevented alterations in expression of other genes sensitive to the second hit of adult stress. These findings suggest that thyroid signaling mediates the deleterious impact of ELS on VTA development, and that temporary treatment of hypothyroidism after ELS may be sufficient to prevent future stress hypersensitivity.
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