The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function

  title={The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function},
  author={Michael Egan and Masami Kojima and Joseph H. Callicott and Terry E. Goldberg and Bhaskar S. Kolachana and Alessandro Bertolino and Eugene Zaitsev and Bert Gold and David Goldman and Michael Dean and Bai Lu and Daniel R. Weinberger},

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Brain-Derived Neurotrophic Factor val66met Polymorphism Affects Human Memory-Related Hippocampal Activity and Predicts Memory Performance
The relationship of the BDNF val66met genotype and hippocampal activity during episodic memory processing using blood oxygenation level-dependent functional magnetic resonance imaging and a declarative memory task in healthy individuals suggests that the basic effects of BDNF signaling on hippocampal function in experimental animals are important in humans.
BNDF modulates normal human hippocampal ageing
It is expected that age-related decline of hippocampal function would be modulated by genetically determined variation in BDNF function, such that BDNF-met allele carriers (expressing diminished regulated secretion of BDNF) would show a more pronounced decrease in memory-dependent hippocampal activity with advancing age relative to BDNF -val/val individuals.
The BDNF Val66Met Polymorphism Impairs NMDA Receptor-Dependent Synaptic Plasticity in the Hippocampus
Results show that the BDNF Val66Met polymorphism has a direct effect on NMDA receptor transmission, which may account for changes in synaptic plasticity in the hippocampus.
BDNF Val66Met Impairs Fluoxetine-Induced Enhancement of Adult Hippocampus Plasticity
The observed effects of the BDNF Val66Met SNP on hippocampal BDNF expression and synaptic plasticity provide a possible mechanistic basis by which this common BDNF SNP may impair efficacy of SSRI drug treatment.
BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression by Down-Regulation of 5-HT3 Receptors
Observations indicate that BDNF val66met polymorphism changes hippocampal synaptic plasticity via down-regulation of 5-HT3a receptors, which may underlie cognition dysfunction of Met allele carriers.
The BDNF Val66Met Polymorphism Impairs Synaptic Transmission and Plasticity in the Infralimbic Medial Prefrontal Cortex
It is reported that spike timing-dependent plasticity (STDP) was absent in the IL-mPFC pyramidal neurons from BDNFMet/Met mice, a mouse that recapitulates the specific phenotypic properties of the human BDNF Val66Met polymorphism.
Brain‐derived neurotrophic factor val66met polymorphism and hippocampal activation during episodic encoding and retrieval tasks
The results suggest that met carriers are able to recruit MTL activity to support successful memory processes, and reductions in cognitive performance observed in prior studies are not a ubiquitous effect associated with variants of the BDNF val66met genotype.
Lack of an association of BDNF Val66Met polymorphism and plasma BDNF with hippocampal volume and memory
Findings suggest that BDNF genotype and plasma BDNF may not be robust predictors for variance in hippocampal volume and memory in middle age and older adult cohorts.
The BDNF val-66-met Polymorphism Affects Neuronal Morphology and Synaptic Transmission in Cultured Hippocampal Neurons from Rett Syndrome Mice
The results suggest that the val-BDNF variant contributes to RTT pathophysiology, and that BDNF-based therapies should take into consideration the BDNF genotype of the RTT individuals.
Impact of the BDNF Val66Met Polymorphism on Cognition
  • I. Dincheva, C. Glatt, F. Lee
  • Biology
    The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
  • 2012
The authors generated a mouse model containing the BDNF Met allele, which they found to replicate the key phenotypes observed in humans and provided further insight into the functional impact of this SNP in vivo.


Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor.
It is suggested that BDNF might have a functional role in the expression of LTP in the hippocampus, and the magnitude of the potentiation, as well as the percentage of cases in which LTP could be induced successfully, was clearly affected.
A role for BDNF in the late-phase of hippocampal long-term potentiation
Involvement of Brain-Derived Neurotrophic Factor in Spatial Memory Formation and Maintenance in a Radial Arm Maze Test in Rats
The results suggest that BDNF plays an important role not only in the formation, but also in the retention and/or recall, of spatial memory.
Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus
The results suggest that BDNF may regulate LTP in developing and adult hippocampus by enhancing synaptic responses to tetanic stimulation, and a TrkB–IgG fusion protein, which scavenges endogenous BDNF11, reduced the synaptic responses in adult hippocampus as well as the magnitude of LTP.
Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities.
The results indicate that endogenous BDNF is critical for the normal development and function of central 5-HT neurons and for the elaboration of behaviors that depend on these nerve cells, and BDNF(+/-) mice may provide a useful model to study human psychiatric disorders attributed to dysfunction of serotonergic neurons.
Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors.
A role for BDNF in the modulation of synaptic transmission in the hippocampus is suggested through a previously unreported mechanism--increased postsynaptic responsiveness via a phosphorylation-dependent pathway.
Signaling mechanisms mediating BDNF modulation of synaptic plasticity in the hippocampus.
The data suggest that BDNF modulation of high-frequency transmission is independent of protein synthesis but requires MAPK and PI3K and yet another signaling pathway to act together in the hippocampus.
Presynaptic Modulation of Synaptic Transmission and Plasticity by Brain-Derived Neurotrophic Factor in the Developing Hippocampus
Results suggest that brain-derived neurotrophic factor acts presynaptically, and the preferential potentiation of highly active synapses by BDNF may have implications in the Hebbian mechanism of synaptic plasticity.