ArticleBiological psychiatry2012
A polymorphism associated with depressive disorders differentially regulates brain derived neurotrophic factor promoter IV activity.
Article in Biological psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial.Journal of neurovirology · 2023Trial
- Peripheral tissue BDNF expression is affected by promoter IV defect and enriched environments in mice: negative hippocampus-intestine and positive thymus-serum-muscle correlations.Molecular medicine (Cambridge, Mass.) · 2025Article
- Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review.International journal of molecular sciences · 2024Review
- Association of HHV‑6 reactivation and SLC6A3 (C>T, rs40184), BDNF (C>T, rs6265), and JARID2 (G>A, rs9383046) single nucleotide polymorphisms in depression.Biomedical reports · 2024Article
- An ancient polymorphic regulatory region within the BDNF gene associated with obesity modulates anxiety-like behaviour in mice and humans.Molecular psychiatry · 2024Article
- Diverse Functions of MultipleBiomolecules · 2023Review
- Heat shock factor HSF1 regulates BDNF gene promoters upon acute stress in the hippocampus, together with pCREB.Journal of neurochemistry · 2023Article
- M3 Receptor Pathway Stimulates Rapid Transcription of the CB1 Receptor Activation through Calcium Signalling and the CNR1 Gene Promoter.International journal of molecular sciences · 2023Article
- Genetics of irritable bowel syndrome: shifting gear via biobank-scale studies.Nature reviews. Gastroenterology & hepatology · 2022Review
- Brain-derived neurotrophic factor and inflammation in depression: Pathogenic partners in crime?World journal of psychiatry · 2022Review
- GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome.Cell genomics · 2021Article
- Influence ofAging and disease · 2020Review
- Perspective: Quality Versus Quantity; Is It Important to Assess the Role of Enhancers in Complex Disease from an In Vivo Perspective?International journal of molecular sciences · 2020Article
- BDNF deficiency and enriched environment treatment affect neurotransmitter gene expression differently across ages.Journal of neurochemistry · 2020Article
- Article
- BDNF genetic variants and methylation: effects on cognition in major depressive disorder.Translational psychiatry · 2019Article
- Non-coding genetic variation shaping mental health.Current opinion in psychology · 2019Review
- The effect of enriched environment across ages: A study of anhedonia and BDNF gene induction.Genes, brain, and behavior · 2018Article
- Differential contribution of cis and trans gene transcription regulatory mechanisms in amygdala and prefrontal cortex and modulation by social stress.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundChanges in brain derived neurotrophic factor (BDNF) expression have been associated with mood disorders and cognitive dysfunction. Transgenic models that overexpress or underexpress BDNF demonstrate similar deficits in cognition and mood. We explored the hypothesis that BDNF expression is controlled by balancing the activity of BDNF promoter IV (BP4) with a negative regulatory region containing a polymorphism associated with cognitive dysfunction and mood disorders.
methodsWe used comparative genomics, transgenic mouse production, and magnetofection of primary neurons with luciferase reporters and signal transduction agonist treatments to identify novel polymorphic cis-regulatory regions that control BP4 activity.
resultsWe show that BP4 is active in the hippocampus, the cortex, and the amygdala and responds strongly to stimuli such as potassium chloride, lithium chloride, and protein kinase C agonists. We also identified a highly conserved sequence 21 kilobase 5' of BP4 that we called BE5.2, which contains rs12273363, a polymorphism associated with decreased BDNF expression, mood disorders, and cognitive decline. BE5.2 modulated the ability of BP4 to respond to different stimuli. Intriguingly, the rarer disease associated allele, BE5.2(C), acted as a significantly stronger repressor of BP4 activity than the more common BE5.2(T) allele.
conclusionsThis study shows that the C allele of rs12273363, which is associated with mood disorder, modulates BP4 activity in an allele-specific manner following cell depolarization or the combined activity of protein kinase A and protein kinase C pathways. The relevance of these findings to the role of BDNF misexpression in mood disorders and cognitive decline is discussed.
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