ArticleFrontiers in behavioral neuroscience2014
Early life stress and serotonin transporter gene variation interact to affect the transcription of the glucocorticoid and mineralocorticoid receptors, and the co-chaperone FKBP5, in the adult rat brain.
Article in Frontiers in behavioral neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- Neurodevelopmental effects of early life stress: PFC and cognition.Neuroscience and biobehavioral reviews · 2026Review
- Long-Term Alterations of Glucocorticoid Receptor Expression and CD4Biomolecules · 2025Article
- Biomarkers of stress resilience: A review.Neuroscience applied · 2024Article
- A comparison of stress reactivity between BTBR and C57BL/6J mice: an impact of early-life stress.Experimental brain research · 2023Article
- Early Life Stress Alters Expression of Glucocorticoid Stress Response Genes and Trophic Factor Transcripts in the Rodent Basal Ganglia.International journal of molecular sciences · 2022Article
- Early Life Stress and Risks for Opioid Misuse: Review of Data Supporting Neurobiological Underpinnings.Journal of personalized medicine · 2021Review
- Early Life Stress Exacerbates Outcome after Traumatic Brain Injury.Journal of neurotrauma · 2021Article
- Maternal Separation Induces Sex-Specific Differences in Sensitivity to Traumatic Stress.Frontiers in behavioral neuroscience · 2021Article
- A Glimpse Into the Sexual Dimorphisms in Major Depressive Disorder Through Epigenetic Studies.Frontiers in neural circuits · 2021Review
- Serotonin homeostasis in the materno-foetal interface at term: Role of transporters (SERT/SLC6A4 and OCT3/SLC22A3) and monoamine oxidase A (MAO-A) in uptake and degradation of serotonin by human and rat term placenta.Acta physiologica (Oxford, England) · 2020Article
- Article
- Neonatal Tactile Stimulation Alters Behaviors in Heterozygous Serotonin Transporter Male Rats: Role of the Amygdala.Frontiers in behavioral neuroscience · 2020Article
- Unraveling the epigenetic landscape of depression: focus on early life stress .Dialogues in clinical neuroscience · 2019Review
- Animal models of PTSD: a challenge to be met.Molecular psychiatry · 2019Review
- Sex-Dependent Modulation of Acute Stress Reactivity After Early Life Stress in Mice: Relevance of Mineralocorticoid Receptor Expression.Frontiers in behavioral neuroscience · 2019Article
- The Serotonin Transporter and Early Life Stress: Translational Perspectives.Frontiers in cellular neuroscience · 2017Review
- Sleep Deprivation-Induced Blood-Brain Barrier Breakdown and Brain Dysfunction are Exacerbated by Size-Related Exposure to Ag and Cu Nanoparticles. Neuroprotective Effects of a 5-HT3 Receptor Antagonist Ondansetron.Molecular neurobiology · 2015Article
- Epigenetic alterations following early postnatal stress: a review on novel aetiological mechanisms of common psychiatric disorders.Clinical epigenetics · 2015Review
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The short allelic variant of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) has been associated with the etiology of major depression by interaction with early life stress (ELS). A frequently observed endophenotype in depression is the abnormal regulation of levels of stress hormones such as glucocorticoids. It is hypothesized that altered central glucocorticoid influence on stress-related behavior and memory processes could underlie the depressogenic interaction of 5-HTTLPR and ELS. One possible mechanism could be the altered expression of the genes encoding the glucocorticoid and mineralocorticoid receptors (GR, MR) and their inhibitory regulator FK506-binding protein 51 (FKBP5) in stress-related forebrain areas. To test this notion, we exposed heterozygous (5-HTT(+/-)) and homozygous (5-HTT(-/-)) serotonin transporter knockout rats and their wildtype littermates (5-HTT(+/+)) to daily 3 h maternal separations from postnatal day 2 to 14. In the medial prefrontal cortex (mPFC) and hippocampus of the adult male offspring, we found that GR, MR, and FKBP5 mRNA levels were affected by ELS × 5-HTT genotype interaction. Specifically, 5-HTT(+/+) rats exposed to ELS showed decreased GR and FKBP5 mRNA in the dorsal and ventral mPFC, respectively. In contrast, 5-HTT(+/-) rats showed increased MR mRNA levels in the hippocampus and 5-HTT(-/-) rats showed increased FKBP5 mRNA in the ventral mPFC after ELS exposure. These findings indicate that 5-HTT genotype determines the specific adaptation of GR, MR, and FKBP5 expression in response to early life adversity. Therefore, altered extra-hypothalamic glucocorticoid signaling should be considered to play a role in the depressogenic interaction of ELS and 5-HTTLPR.
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