Abstract
BackgroundThe brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) may impact on the in-vivo binding of important serotonergic structures such as the serotonin transporter (5-HTT) and the serotonin-1A (5-HT1A) receptor. Previous positron emission tomography (PET) studies on the association between Val66Met and 5-HTT and 5-HT1A binding potential (BPND) have demonstrated equivocal results.MethodsWe conducted an imaging genetics study investigating the effect of Val66Met genotype on 5-HTT or 5-HT1A BPND in 92 subjects. Forty-one subjects (25 healthy subjects and 16 depressive patients) underwent genotyping for Val66Met and PET imaging with the 5-HTT specific radioligand [11C]DASB. Additionally, in 51 healthy subjects Val66Met genotypes and 5-HT1A binding with the radioligand [carbonyl-11C]WAY-100635 were ascertained. Voxel-wise and region of interest-based analyses of variance were used to examine the influence of Val66Met on 5-HTT and 5-HT1A BPND.ResultsNo significant differences of 5-HTT nor 5-HT1A BPND between BDNF Val66Met genotype groups (val/val vs. met-carrier) were detected. There was no interaction between depression and Val66Met genotype status.ConclusionIn line with previous data, our work confirms an absent effect of BDNF Val66Met on two major serotonergic structures. These results could suggest that altered protein expression associated with genetic variants, might be compensated in vivo by several levels of unknown feedback mechanisms. In conclusion, Val66Met genotype status is not associated with changes of in-vivo binding of 5-HTT and 5-HT1A receptors in human subjects.
Highlights
The brain-derived neurotrophic factor (BDNF) is the most prominent member in the neurotrophin family and involved in development and activity-dependent regulation of neuronal structures [1]
We modeled 5-HT1A BPND as previously described by our group using the insula as receptor-rich region and the cerebellum as receptor-poor region [23]
In the voxel-wise analysis there was no significant association of BDNF genotype (GG vs. A-carrier) status with 5-HT1A BPND (Ftest: all p.0.05 family-wise error rate (FWE) corr. and all p.0.001 uncorr.)
Summary
The brain-derived neurotrophic factor (BDNF) is the most prominent member in the neurotrophin family and involved in development and activity-dependent regulation of neuronal structures [1]. BDNF is linked with at least three major intracellular signaling cascades: the phosphoinositide-3 kinase pathway enabling cell survival, the phospholipase-gamma pathway effecting synaptic plasticity and the mitogen-activated protein kinase pathway associated with neuronal differentiation and neurite outgrowth [3]. Thereby, BDNF is a major factor in the proper development and plastic regulation of the central nervous system and highly active in limbic structures such as the hippocampus and the amygdala, where long-term potentiation, learning and memory are facilitated [7]. The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) may impact on the in-vivo binding of important serotonergic structures such as the serotonin transporter (5-HTT) and the serotonin-1A (5-HT1A) receptor. Previous positron emission tomography (PET) studies on the association between Val66Met and 5-HTT and 5-HT1A binding potential (BPND) have demonstrated equivocal results
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