ArticleMolecular psychiatry2022
Impact of Fkbp5 × early life adversity × sex in humanised mice on multidimensional stress responses and circadian rhythmicity.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Multilevel sex-influenced neurobiological signatures of early life adversity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Standardized chronic restraint stress protocols reveal dynamic evolution of behavioral adaptations in male mice: implications for translational neuroscience.Molecular psychiatry · 2026Article
- Corticosterone-linked microglial activity underpins sexually dimorphic neuroplasticity after ketamine anesthesia.Science advances · 2026Article
- TGR5 is essential for protecting from chronic stress-induced learning and memory impairments in mice by modulating inflammation associated with the gut-brain axis.Journal of neuroinflammation · 2026Article
- Review
- The rs1360780 Variant ofGenes · 2025Review
- A glucocorticoid-regulating molecule, Fkbp5, may interact with mitogen-activated protein kinase signaling in the organ of Corti of mice cochleae.Scientific reports · 2025Article
- Childhood trauma is associated with perceived stress and hair cortisol levels characterized by the BDNF Val66Met genotype and sex.Frontiers in psychiatry · 2025Article
- Sex-specific fear acquisition following early life stress is linked to amygdala and hippocampal purine and glutamate metabolism.Communications biology · 2024Article
- Targeting glucocorticoid receptor signaling pathway for treatment of stress-related brain disorders.Pharmacological reports : PR · 2024Review
- DNA methylation patterns of FKBP5 regulatory regions in brain and blood of humanized mice and humans.Molecular psychiatry · 2024Article
- Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder.Nature communications · 2024Article
- Article
- Article
- Neurobiological mechanisms of mood disorders: Stress vulnerability and resilience.Frontiers in behavioral neuroscience · 2022Review
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cumulative load of genetic predisposition, early life adversity (ELA) and lifestyle shapes the prevalence of psychiatric disorders. Single nucleotide polymorphisms (SNPs) in the human FKBP5 gene were shown to modulate disease risk. To enable investigation of disease-related SNPs in behaviourally relevant context, we generated humanised mouse lines carrying either the risk (AT) or the resiliency (CG) allele of the rs1360780 locus and exposed litters of these mice to maternal separation. Behavioural and physiological aspects of their adult stress responsiveness displayed interactions of genotype, early life condition, and sex. In humanised females carrying the CG- but not the AT-allele, ELA led to altered HPA axis functioning, exploratory behaviour, and sociability. These changes correlated with differential expression of genes in the hypothalamus, where synaptic transmission, metabolism, and circadian entrainment pathways were deregulated. Our data suggest an integrative role of FKBP5 in shaping the sex-specific outcome of ELA in adulthood.
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