ArticleNeurobiology of disease2021
The BDNF Val66Met polymorphism (rs6265) enhances dopamine neuron graft efficacy and side-effect liability in rs6265 knock-in rats.
Article in Neurobiology of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 24 citations in OpenAlex.
- Prenatal and neonatal housing conditions affect anxiety-like behavior in adulthood in rats and interact with brain-derived neurotrophic factor (BDNF) Val66Met to alter expression of BDNF and stress markers in the ventral hippocampus.Frontiers in molecular neuroscience · 2026Article
- BDNF genotype associated with changes in cortical thickness, severity of symptoms, and cognitive impairments in mild traumatic brain injury.Molecular brain · 2025Article
- Article
- Investigating the role of the brain-derived neurotrophic factor Val66Met polymorphism in repetitive mild traumatic brain injury outcomes in rats.Behavioral and brain functions : BBF · 2025Article
- Advancing age and the rs6265 BDNF SNP are permissive to graft-induced dyskinesias in parkinsonian rats.NPJ Parkinson's disease · 2024Article
- The impact of the interaction between BDNF rs7103411 gene polymorphism and social activities on mild cognitive impairment in community-dwelling elderly adults.Frontiers in psychiatry · 2024Article
- Interaction of Brain-derived Neurotrophic Factor, Exercise, and Fear Extinction: Implications for Post-traumatic Stress Disorder.Current neuropharmacology · 2024Review
- Article
- Shared miRNA landscapes of COVID-19 and neurodegeneration confirm neuroinflammation as an important overlapping feature.Frontiers in molecular neuroscience · 2023Article
- Brain-derived neurotrophic factor rs6265 (Val66Met) single nucleotide polymorphism as a master modifier of human pathophysiology.Neural regeneration research · 2023Review
- New Frontiers in Neurodegeneration and Regeneration Associated with Brain-Derived Neurotrophic Factor and the rs6265 Single Nucleotide Polymorphism.International journal of molecular sciences · 2022Review
- The BDNF Val66Met Polymorphism Does Not Increase Susceptibility to Activity-Based Anorexia in Rats.Biology · 2022Article
- Behavioral phenotyping of a rat model of the BDNF Val66Met polymorphism reveals selective impairment of fear memory.Translational psychiatry · 2022Article
- Article
- Induction and Assessment of Levodopa-induced Dyskinesias in a Rat Model of Parkinson's Disease.Journal of visualized experiments : JoVE · 2021Article
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11 authors at 3 institutions in 1 country.
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Abstract
Prevalent in approximately 20% of the worldwide human population, the rs6265 (also called 'Val66Met') single nucleotide polymorphism (SNP) in the gene for brain-derived neurotrophic factor (BDNF) is a common genetic variant that can alter therapeutic responses in individuals with Parkinson's disease (PD). Possession of the variant Met allele results in decreased activity-dependent release of BDNF. Given the resurgent worldwide interest in neural transplantation for PD and the biological relevance of BDNF, the current studies examined the effects of the rs6265 SNP on therapeutic efficacy and side-effect development following primary dopamine (DA) neuron transplantation. Considering the significant reduction in BDNF release associated with rs6265, we hypothesized that rs6265-mediated dysfunctional BDNF signaling contributes to the limited clinical benefit observed in a subpopulation of PD patients despite robust survival of grafted DA neurons, and further, that this mutation contributes to the development of aberrant graft-induced dyskinesias (GID). To this end, we generated a CRISPR knock-in rat model of the rs6265 BDNF SNP to examine for the first time the influence of a common genetic polymorphism on graft survival, functional efficacy, and side-effect liability, comparing these parameters between wild-type (Val/Val) rats and those homozygous for the variant Met allele (Met/Met). Counter to our hypothesis, the current research indicates that Met/Met rats show enhanced graft-associated therapeutic efficacy and a paradoxical enhancement of graft-derived neurite outgrowth compared to wild-type rats. However, consistent with our hypothesis, we demonstrate that the rs6265 genotype in the host rat is strongly linked to development of GID, and that this behavioral phenotype is significantly correlated with neurochemical signatures of atypical glutamatergic neurotransmission by grafted DA neurons.
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