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Published on: February 28, 2025
The brain-derived neurotrophic factor VAL68MET polymorphism modulates how developmental ethanol exposure impacts the
C W Bird1, B C Baculis1, J J Mayfield1
1Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
The BDNF val66met gene variant influences fetal alcohol spectrum disorder (FASD) severity. Developmental alcohol exposure impacts brain development and behavior differently in mice with this common genetic polymorphism.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Fetal alcohol spectrum disorders (FASDs) result from prenatal alcohol exposure, causing diverse neurodevelopmental deficits.
- Genetic factors, including single nucleotide polymorphisms, can influence individual susceptibility to FASDs.
- The brain-derived neurotrophic factor (BDNF) val66met polymorphism affects neuronal function and is linked to neuropsychiatric disorders.
Purpose of the Study:
- To investigate how the BDNF val66met polymorphism modulates the effects of developmental ethanol (EtOH) exposure on neurodevelopment and behavior.
- To identify potential genetic risk factors influencing FASD severity.
Main Methods:
- Utilized transgenic mice homozygous for either the valine (BDNFval/val) or methionine (BDNFmet/met) variant.
- Modeled human second and third trimester EtOH exposure using vapor chambers during specific gestational and postnatal periods.
- Assessed neurodevelopmental changes (hippocampal volume, neurogenesis) and behavioral outcomes (anxiety, fear conditioning) at juvenile and adult stages.
Main Results:
- EtOH exposure reduced dentate gyrus and CA1 hippocampal volumes in juvenile BDNFmet/met mice, but not BDNFval/val mice.
- Adult BDNFmet/met mice exposed to EtOH exhibited reduced anxiety-like behavior and disrupted trace fear conditioning, particularly males.
- Adult male BDNFval/val mice exposed to EtOH showed reduced neurogenesis in the ventral hippocampus.
Conclusions:
- The BDNF val66met polymorphism significantly modulates the neurodevelopmental and behavioral consequences of prenatal alcohol exposure.
- This common genetic variant represents a potential risk factor influencing FASD severity in humans.
- Findings highlight the complex interplay between genetics and environmental factors in FASD pathogenesis.
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