ArticleBrain, behavior, & immunity - health2020
FKBP5 and early life stress affect the hippocampus by an age-dependent mechanism.
Article in Brain, behavior, & immunity - health, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- Mechanisms by which sevoflurane affects cognitive function in aged marmosets and mice: up-regulation of FKBP5 expression in brain microglia.Medical gas research · 2026Article
- Reconceptualizing bipolar disorder through an integrative biological lens: synthesis, convergence, and emerging directions.Frontiers in integrative neuroscience · 2026Review
- Long-Term Alterations of Glucocorticoid Receptor Expression and CD4Biomolecules · 2025Article
- Review
- Sensory neurostimulation promotes stress resilience with frequency-specificity.bioRxiv : the preprint server for biology · 2025Article
- Lithium Treatment Increases FKBP5 Protein but Not mRNA Expression in the Pituitary Gland of Depressive-like Rats.Brain sciences · 2025Article
- FKBP51 in glutamatergic forebrain neurons promotes early life stress inoculation in female mice.Nature communications · 2025Article
- Peripheral DNA Methylation of Cortisol- and Serotonin-Related Genes Predicts Hippocampal Volume in a Pediatric Population.Biological psychiatry global open science · 2025Article
- Sex-specific fear acquisition following early life stress is linked to amygdala and hippocampal purine and glutamate metabolism.Communications biology · 2024Article
- Early-life obesogenic environment integrates immunometabolic and epigenetic signatures governing neuroinflammation.Brain, behavior, & immunity - health · 2024Article
- Single Nuclei Transcriptomics Reveals Obesity-Induced Endothelial and Neurovascular Dysfunction: Implications for Cognitive Decline.International journal of molecular sciences · 2024Article
- Dissecting the Long-Term Effect of Stress Early in Life onBiomolecules · 2024Article
- Biomarkers of stress resilience: A review.Neuroscience applied · 2024Article
- IL-1R1 signaling in TBI: assessing chronic impacts and neuroinflammatory dynamics in a mouse model of mild closed-head injury.Journal of neuroinflammation · 2023Article
- Sex-specific and opposed effects of FKBP51 in glutamatergic and GABAergic neurons: Implications for stress susceptibility and resilience.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Associations of psychiatric disease and ageing with FKBP5 expression converge on superficial layer neurons of the neocortex.Acta neuropathologica · 2023Article
- Adverse maternal environment alters Oprl1 variant expression in mouse hippocampus.Anatomical record (Hoboken, N.J. : 2007) · 2023Article
- Neurogenesis in aging and age-related neurodegenerative diseases.Ageing research reviews · 2022Review
- Central and Peripheral Immune Dysregulation in Posttraumatic Stress Disorder: Convergent Multi-Omics Evidence.Biomedicines · 2022Review
- Early Adversity and Accelerated Brain Aging: A Mini-Review.Frontiers in molecular neuroscience · 2022Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Early life stress (ELS) adversely affects the brain and is commonly associated with the etiology of mental health disorders, like depression. In addition to the mood-related symptoms, patients with depression show dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, increased peripheral inflammation, and structural brain alterations. Although the underlying causes are unknown, polymorphisms in the FK506-binding protein 5 (FKBP5) gene, a regulator of glucocorticoid receptor (GR) activity, interact with childhood adversities to increase vulnerability to depressive disorders. We hypothesized that high FKBP5 protein levels combined with early life stress (ELS) would alter the HPA axis and brain, promoting depressive-like behaviors. To test this, we exposed males and females of a mouse model overexpressing FKBP5 in the brain (rTgFKBP5 mice), or littermate controls, to maternal separation for 14 days after birth. Then, we evaluated neuroendocrine, behavioral, and brain changes in young adult and aged mice. We observed lower basal corticosterone (CORT) levels in rTgFKBP5 mice, which was exacerbated in females. Aged, but not young, rTgFKBP5 mice showed increased depressive-like behaviors. Moreover, FKBP5 overexpression reduced hippocampal neuron density in aged mice, while promoting markers of microglia expression, but these effects were reversed by ELS. Together, these results demonstrate that high FKBP5 affects basal CORT levels, depressive-like symptoms, and numbers of neurons and microglia in the hippocampus in an age-dependent manner.
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