ArticleActa neuropathologica communications2019
Plasminogen Activator Inhibitor-1 (PAI-1) deficiency predisposes to depression and resistance to treatments.
Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 3 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Comparing the effect of fluoxetine, escitalopram, and sertraline, on the level of BDNF and depression in preclinical and clinical studies: a systematic review.European journal of clinical pharmacology · 2024Pooled it
- Probiotics for the treatment of depression and its comorbidities: A systemic review.Frontiers in cellular and infection microbiology · 2023Pooled it
- Serum plasminogen activator inhibitor-1 levels in patients with major depressive disorder vs. healthy controls: a systematic review and meta-analysis.Trends in psychiatry and psychotherapy · 2023Pooled it
- Targeting PAI-1 with TM5441 Mitigates Chronic Social Stress-Induced Anxiety-Like Behavior and Stress-Induced Increases in Ethanol Intake and Preference.Neurochemical research · 2026Article
- TM5441, a PAI-1 inhibitor, attenuates chronic stress-induced anxio-depressive-like behaviors by restoring the hippocampal PAI-1/tPA/BDNF axis.Psychopharmacology · 2026Article
- Mode-dependent effects of chemical, intermittent, and hypobaric hypoxia on HIF-1α, HIF-2α, HIF-3α, PACAP, and PAI mRNA expression in the single prolonged stress model of PTSD.Frontiers in neuroscience · 2026Review
- Biomarkers of Endothelial Dysfunction in Cerebral Small Vessel Disease.Noro psikiyatri arsivi · 2026Article
- The Plasminogen Activation System in the Central Nervous System: Implications for Epilepsy and Neuropsychiatric Disorders.International journal of molecular sciences · 2025Review
- Article
- Treatment-resistant depression: molecular mechanisms and management.Molecular biomedicine · 2024Review
- Shared biological mechanisms of depression and obesity: focus on adipokines and lipokines.Aging · 2023Review
- Plasminogen Activator Inhibitor-1: Potential Inflammatory Marker in Late-life Depression.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2023Article
- Glucocorticoid-Responsive Tissue Plasminogen Activator (tPA) and Its Inhibitor Plasminogen Activator Inhibitor-1 (PAI-1): Relevance in Stress-Related Psychiatric Disorders.International journal of molecular sciences · 2023Review
- Shared Genetic Regulatory Networks Contribute to Neuropathic and Inflammatory Pain: Multi-Omics Systems Analysis.Biomolecules · 2022Article
- Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue.Nature communications · 2022Article
- Article
- Bioinformatics and Network Pharmacology-Based Approaches to Explore the Potential Mechanism of the Antidepressant Effect of Cyperi Rhizoma through Soothing the Liver.Evidence-based complementary and alternative medicine : eCAM · 2021Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Major depressive disorder (MDD) is one of the most frequent psychiatric illnesses, leading to reduced quality of life, ability to work and sociability, thus ranking among the major causes of disability and morbidity worldwide. To date, genetic and environmental determinants of MDD remain mostly unknown. Here, we investigated whether and how the Plasminogen Activator Inhibitor-1 (PAI-1) may contribute to MDD. We first examined the phenotype of PAI-1 knockout (PAI-1-/-) and wild-type (PAI-1+/+) male mice with a range of behavioral tests assessing depressive-like behaviors (n = 276). We next investigated the mechanisms relating PAI-1 to MDD using molecular, biochemical and pharmacological analyzes. We demonstrate here that PAI-1 plays a key role in depression by a mechanism independent of the tissue-type Plasminogen Activator (tPA) - Brain-Derived Neurotrophic Factor (BDNF) axis, but associated with impaired metabolisms of serotonin and dopamine. Our data also reveal that PAI-1 interferes with therapeutic responses to selective serotonin reuptake inhibitors (escitalopram, fluoxetine). We thus highlight a new genetic preclinical model of depression, with the lack of PAI-1 as a factor of predisposition to MDD. Altogether, these original data reveal that PAI-1 should be now considered as a key player of MDD and as a potential target for the development of new drugs to cure depressive patients resistant to current treatments.
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Registered trials
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