ArticleScientific reports2020
Human BDNF/TrkB variants impair hippocampal synaptogenesis and associate with neurobehavioural abnormalities.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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Who cites it
31 citing papers in PubMed, 69 citations in OpenAlex.
- Evaluating depressive symptoms, BDNF Val66Met, and APOE-ε4 as moderators of response to computerized cognitive training in heart failure.Heart & lung : the journal of critical careTrial
- Functional Mapping of Neurodevelopmental Disease Pathways to Key Neurodevelopmental Processes Represented in the Developmental Neurotoxicity In Vitro Testing Battery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeted Next-Generation Sequencing of the Leptin-Melanocortin Pathway in Severe Obesity.Obesity (Silver Spring, Md.) · 2026Article
- Review
- Effects of Rare Coding Variants in Severe Early-Onset Obesity Genes in the Population-Based UK Biobank Study.The Journal of clinical endocrinology and metabolism · 2025Article
- The expanding landscape of genetic causes of obesity.Pediatric research · 2025Review
- Intermittent hypoxia-induced enhancements in corticospinal excitability predict gains in motor learning and metabolic efficiency.Scientific reports · 2025Article
- Flavonoid chrysin activates both TrkB and FGFR1 receptors while upregulates their endogenous ligands such as brain derived neurotrophic factor to promote human neurogenesis.Cell proliferation · 2025Article
- Updates on Rare Genetic Variants, Genetic Testing, and Gene Therapy in Individuals With Obesity.Current obesity reports · 2024Review
- Influence of Genetic Polymorphisms on Cognitive Function According to Dietary Exposure to Bisphenols in a Sample of Spanish Schoolchildren.Nutrients · 2024Article
- Intermittent Hypoxia-Induced Enhancements in Corticospinal Excitability Predict Gains in Motor Learning and Metabolic Efficiency.Research square · 2024Article
- Effect of vitamin E on doxorubicin and paclitaxel-induced memory impairments in male rats.Cancer chemotherapy and pharmacology · 2024Article
- Alzheimer's therapeutic development: shifting neurodegeneration to neuroregeneration.Trends in pharmacological sciences · 2024Review
- TrkB phosphorylation in serum extracellular vesicles correlates with cognitive function enhanced by ergothioneine in humans.NPJ science of food · 2024Article
- In silico analysis of the Val66Met mutation in BDNF protein: implications for psychological stress.AMB Express · 2024Article
- Article
- Chromosomal deletions on 16p11.2 encompassing SH2B1 are associated with accelerated metabolic disease.Cell reports. Medicine · 2023Article
- Butyrate ameliorates quinolinic acid-induced cognitive decline in obesity models.The Journal of clinical investigation · 2023Article
- Roles of microglia in adult hippocampal neurogenesis in depression and their therapeutics.Frontiers in immunology · 2023Review
- Neurotrophin signalling in the human nervous system.Frontiers in molecular neuroscience · 2023Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
Brain-derived neurotrophic factor (BDNF) signals through its high affinity receptor Tropomyosin receptor kinase-B (TrkB) to regulate neuronal development, synapse formation and plasticity. In rodents, genetic disruption of Bdnf and TrkB leads to weight gain and a spectrum of neurobehavioural phenotypes. Here, we functionally characterised a de novo missense variant in BDNF and seven rare variants in TrkB identified in a large cohort of people with severe, childhood-onset obesity. In cells, the E183K BDNF variant resulted in impaired processing and secretion of the mature peptide. Multiple variants in the kinase domain and one variant in the extracellular domain of TrkB led to a loss of function through multiple signalling pathways, impaired neurite outgrowth and dominantly inhibited glutamatergic synaptogenesis in hippocampal neurons. BDNF/TrkB variant carriers exhibited learning difficulties, impaired memory, hyperactivity, stereotyped and sometimes, maladaptive behaviours. In conclusion, human loss of function BDNF/TrkB variants that impair hippocampal synaptogenesis may contribute to a spectrum of neurobehavioural disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.