ArticleThe international journal of neuropsychopharmacology2015
Expression and Dendritic Trafficking of BDNF-6 Splice Variant are Impaired in Knock-In Mice Carrying Human BDNF Val66Met Polymorphism.
Article in The international journal of neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 63 citations in OpenAlex.
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- Prenatal maternal life adversity impacts on learning and memory in offspring: implication to transgenerational epigenetic inheritance.Frontiers in neuroscience · 2025Article
- The intriguing role of platelets as custodians of brain-derived neurotrophic factor.Research and practice in thrombosis and haemostasis · 2024Article
- Chemical LTP induces confinement of BDNF mRNA under dendritic spines and BDNF protein accumulation inside the spines.Frontiers in molecular neuroscience · 2024Article
- Transcranial Direct Current Stimulation in neurogenetic syndromes: new treatment perspectives for Down syndrome?Frontiers in cellular neuroscience · 2024Article
- Behavioral phenotyping of a rat model of the BDNF Val66Met polymorphism reveals selective impairment of fear memory.Translational psychiatry · 2022Article
- The stressed synapse 2.0: pathophysiological mechanisms in stress-related neuropsychiatric disorders.Nature reviews. Neuroscience · 2022Review
- Brain-derived neurotrophic factor in Alzheimer's disease and its pharmaceutical potential.Translational neurodegeneration · 2022Review
- Drinking Pattern in Intermittent Access Two-Bottle-Choice Paradigm in Male Wistar Rats Is Associated with Exon-Specific BDNF Expression in the Hippocampus During Early Abstinence.Journal of molecular neuroscience : MN · 2021Article
- Review
- Disturbed Balance of Inhibitory Signaling Links Hearing Loss and Cognition.Frontiers in neural circuits · 2021Article
- The BDNF Val66Met polymorphism (rs6265) enhances dopamine neuron graft efficacy and side-effect liability in rs6265 knock-in rats.Neurobiology of disease · 2021Article
- Negative association between left prefrontal GABA concentration and BDNF serum concentration in young adults.Heliyon · 2020Article
- The Role of Dendritic Brain-Derived Neurotrophic Factor Transcripts on Altered Inhibitory Circuitry in Depression.Biological psychiatry · 2019Article
- Glutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments.The international journal of neuropsychopharmacology · 2019Review
- BDNF Val66Met Genetic Polymorphism Results in Poor Recovery Following Repeated Mild Traumatic Brain Injury in a Mouse Model and Treatment With AAV-BDNF Improves Outcomes.Frontiers in neurology · 2019Article
- Sub-Chronic Stress Exacerbates the Pro-Thrombotic Phenotype in BDNFInternational journal of molecular sciences · 2018Article
- Translational profiling of stress-induced neuroplasticity in the CA3 pyramidal neurons of BDNF Val66Met mice.Molecular psychiatry · 2018Article
- Visualizing BDNF Transcript Usage During Sound-Induced Memory Linked Plasticity.Frontiers in molecular neuroscience · 2018Article
- The Role of BDNF in Peripheral Nerve Regeneration: Activity-Dependent Treatments and Val66Met.Frontiers in cellular neuroscience · 2018Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe human Val66Met polymorphism in brain-derived neurotrophic factor (BDNF), a key factor in neuroplasticity, synaptic function, and cognition, has been implicated in the pathophysiology of neuropsychiatric and neurodegenerative disorders. BDNF is encoded by multiple transcripts with distinct regulation and localization, but the impact of the Val66Met polymorphism on BDNF regulation remains unclear.
methodsIn BDNF Val66Met knock-in mice, which recapitulate the phenotypic hallmarks of individuals carrying the BDNF(Met) allele, we measured expression levels, epigenetic changes at promoters, and dendritic trafficking of distinct BDNF transcripts using quantitative PCR, chromatin immunoprecipitation (ChIP), and in situ hybridization.
resultsBDNF-4 and BDNF-6 transcripts were reduced in BDNF(Met/Met) mice, compared with BDNF(Val/Val) mice. ChIP for acetyl-histone H3, a marker of active gene transcription, and trimethyl-histone-H3-Lys27 (H3K27me3), a marker of gene repression, showed higher H3K27me3 binding to exon 5, 6, and 8 promoters in BDNF(Met/Met). The H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) is involved in epigenetic regulation of BDNF expression, because in neuroblastoma cells BDNF expression was increased both by short interference RNA for EZH2 and incubation with 3-deazaneplanocin A, an inhibitor of EZH2. In situ hybridization for BDNF-2, BDNF-4, and BDNF-6 after pilocarpine treatment showed that BDNF-6 transcript was virtually absent from distal dendrites of the CA1 and CA3 regions in BDNF(Met/Met) mice, while no changes were found for BDNF-2 and BDNF-4.
conclusionsImpaired BDNF expression and dendritic targeting in BDNF(Met/Met) mice may contribute to reduced regulated secretion of BDNF at synapses, and may be a specific correlate of pathology in individuals carrying the Met allele.
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