Genetic variation in brain-derived neurotrophic factor val66met allele is associated with altered serotonin-1A receptor binding in human brain.
Genetic variation in brain-derived neurotrophic factor val66met allele is associated with altered serotonin-1A receptor binding in human brain.
复制标题
脑源性神经营养因子 val66met 等位基因的遗传变异与人脑中 5-羟色胺-1A 受体结合的改变有关。
DOI：
10.1016/j.neuroimage.2014.02.027
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发表时间：
2014
期刊：
影响因子：
5.7
通讯作者：
Parsey,RaminV
中科院分区：
文献类型：
--
作者：
Lan,MartinJ;Ogden,RTodd;Huang,Yung-Yu;Oquendo,MariaA;Sullivan,GregoryM;Miller,Jeffrey;Milak,Matthew;Mann,JJohn;Parsey,RaminV
脑源性神经营养因子（BDNF）调节脑突触可塑性。BDNF影响血清素信号，增加脑组织中的血清素水平，防止血清素神经元退化。这些影响几乎没有在人脑中进行过研究。我们检测了BDNF基因的功能性val66met多态性与体内5-羟色胺1A （5-HT1A）受体结合的关系。50名健康志愿者（HV）和50名急性抑郁、未服药的重度抑郁症（MDD）患者接受了5- ht1a受体配体[11C]WAY-100635和代谢物校正的动脉输入功能的PET扫描。以性别和5- ht1a受体启动子功能多态性的C-1019G基因型为协变量，采用线性混合效应模型比较了met等位基因携带者（met/met和val/met）和非携带者（val/val）在13个感兴趣的大脑区域中的5- ht1a受体结合电位（BPF，与可用受体数量成正比）。诊断与等位基因之间存在交互作用（F = 4.23, df = 1,94, p = 0.042）， met等位基因携带者的bpf值在HV组中比非met等位基因携带者低17.4% (t = 2.6, df = 96, p = 0.010)，而在MDD组中则无交互作用（t = - 0.4, df = 96, p = 0.58）。这些数据与一个模型一致，即val66met多态性的met等位基因导致5-羟色胺突触的增殖减少，从而减少5- ht1a受体。然而，在重度抑郁症中，无法检测到val66met多态性的影响，这可能是由于情绪障碍中5- ht1a受体过度表达的天花板效应。
Brain Derived Neurotrophic Factor (BDNF) regulates brain synaptic plasticity. BDNF affects serotonin signaling, increases serotonin levels in brain tissue and prevents degeneration of serotonin neurons. These effects have hardly been studied in human brain. We examined the relationship of the functional val66met polymorphism of the BDNF gene to serotonin 1A (5-HT1A) receptor bindingin vivo. 50 healthy volunteers (HV) and 50 acutely depressed, unmedicated patients with major depressive disorder (MDD) underwent PET scanning with the 5-HT1Areceptor ligand, [11C]WAY-100635 and a metabolite corrected arterial input function. A linear mixed effects model compared 5-HT1Areceptor binding potential (BPF, proportional to the number of available receptors) in 13 brain regions of interest between met allele carriers (met/met and val/met) and noncarriers (val/val) using sex and C-1019G genotype of the 5-HT1Areceptor promoter functional polymorphism as covariates. There was an interaction between diagnosis and allele (F = 4.23, df = 1, 94, p = 0.042), such that met allele carriers had 17.4% lower BPFthan non-met carriers in the HV group (t = 2.6, df = 96, p = 0.010), but not in the MDD group (t = − 0.4, df = 96, p = 0.58). These data are consistent with a model where the met allele of the val66met polymorphism causes less proliferation of serotonin synapses, and consequently fewer 5-HT1Areceptors. In MDD, however, the effect of the val66met polymorphism is not detectable, possibly due to a ceiling effect of over-expression of 5-HT1Areceptors in mood disorders.