Brain-derived neurotrophic factor genotype impacts the prenatal cocaine-induced mouse phenotype.

Developmental Neuroscience
Zeeba D KabirB E Kosofsky

Abstract

Prenatal cocaine exposure leads to persistent alterations in the growth factor brain-derived neurotrophic factor (BDNF), particularly in the medial prefrontal cortex (mPFC) and hippocampus, brain regions important in cognitive functioning. BDNF plays an important role in the strengthening of existing synaptic connections as well as in the formation of new contacts during learning. A single nucleotide polymorphism in the BDNF gene (Val66Met), leading to a Met substitution for Val at codon 66 in the prodomain, is common in human populations, with an allele frequency of 20-30% in Caucasians. To study the interaction between prenatal cocaine exposure and BDNF, we have utilized a line of BDNF Val66Met transgenic mice on a Swiss Webster background in which BDNF(Met) is endogenously expressed. Examination of baseline levels of mature BDNF protein in the mPFC of prenatally cocaine-treated wild-type (Val66Val) and Val66Met mice revealed significantly lower levels compared to prenatally saline-treated mice. In contrast, in the hippocampus of prenatally saline- and cocaine-treated adult Val66Met mice, there were significantly lower levels of mature BDNF protein compared to Val66Val mice. In extinction of a conditioned fear, we found that ...Continue Reading

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Citations

Sep 17, 2013·Biological Psychiatry·John D Elsworth, Robert H Roth
Apr 30, 2015·Physiology & Behavior·Xiaolin ZhuXiangyang Zhang
Jun 28, 2016·Birth Defects Research. Part C, Embryo Today : Reviews·Melissa M MartinGregg D Stanwood
Dec 7, 2016·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Zeeba D KabirAnjali M Rajadhyaksha
Aug 7, 2016·PloS One·Andres StuckyHoau-Yan Wang

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