The brain‐derived neurotrophic factor VAL68MET polymorphism modulates how developmental ethanol exposure impacts the hippocampus

• DOI: 10.1111/gbb.12484
• Publication Date: 2018-04-25T02:01:24Z
• Authors: C. W. Bird; B. C. Baculis; J. J. Mayfield; G. J. Chavez; T. Ontiveros; D. J. Paine; A. J. Marks; A. L. Gonzales; D. Ron; C. F. Valenzuela
• Keywords: Male; Ethanol; Brain-Derived Neurotrophic Factor; Conditioning, Classical; Mutation, Missense; Central Nervous System Depressants; Fear; Anxiety; Hippocampus; Polymorphism, Single Nucleotide; 3. Good health; Mice; 03 medical and health sciences; 0302 clinical medicine; Pregnancy; Prenatal Exposure Delayed Effects; Animals; Female

Prenatal exposure to alcohol causes a wide range of deficits known as fetal spectrum disorders (FASDs). Many factors determine vulnerability developmental including timing and pattern exposure, nutrition genetics. Here, we characterized how prevalent single nucleotide polymorphism in the human brain‐derived neurotrophic factor (BDNF) gene (val66met) modulates FASDs severity. This disrupts BDNF's intracellular trafficking activity‐dependent secretion, has been linked increased incidence neuropsychiatric such depression anxiety. We hypothesized that ethanol (EtOH) more severely affects mice carrying this polymorphism. used transgenic homozygous for either valine (BDNF val/val ) or methionine met/met residue 68, equivalent 66 humans. To model EtOH during second third trimesters pregnancy, exposed vapor chambers gestational days 12 19 postnatal 2 9. found reduces cell layer volume dentate gyrus CA1 hippocampal regions BDNF but not juvenile period (postnatal day 15). During adulthood, reduced anxiety‐like behavior disrupted trace fear conditioning mice, with most effects observed males. adult neurogenesis only ventral hippocampus male mice. These studies show val66met modulates, complex manner, identify novel genetic risk may regulate severity