Christian B T, Fox A S, Oler J A, Vandehey N T, Murali D, Rogers J, Oakes T R, Shelton S E, Davidson R J, Kalin N H
Department of Psychiatry, Harlow Primate Center, University of Wisconsin-Madison, USA.
Neuroimage. 2009 Oct 1;47(4):1230-6. doi: 10.1016/j.neuroimage.2009.05.090. Epub 2009 Jun 6.
The length polymorphism of the serotonin (5-HT) transporter gene promoter region has been implicated in altered 5-HT function and, in turn, neuropsychiatric illnesses, such as anxiety and depression. The nonhuman primate has been used as a model to study anxiety-related mechanisms in humans based upon similarities in behavior and the presence of a similar 5-HT transporter gene polymorphism. Stressful and threatening contexts in the nonhuman primate model have revealed 5-HT transporter genotype dependent differences in regional glucose metabolism. Using the rhesus monkey, we examined the extent to which serotonin transporter genotype is associated with 5-HT transporter binding in brain regions implicated in emotion-related pathology.
Genotype data and high resolution PET scans were acquired in 29 rhesus (Macaca mulatta) monkeys. [C-11]DASB dynamic PET scans were acquired for 90 min in the anesthetized animals and images of distribution volume ratio (DVR) were created to serve as a metric of 5-HT transporter binding for group comparison based on a reference region method of analysis. Regional and voxelwise statistical analysis were performed with corrections for anatomical differences in gray matter probability, sex, age and radioligand mass.
There were no significant differences when comparing l/l homozygotes with s-carriers in the regions of the brain implicated in anxiety and mood related illnesses (amygdala, striatum, thalamus, raphe nuclei, temporal and prefrontal cortex). There was a significant sex difference in 5-HT transporter binding in all regions with females having 18%-28% higher DVR than males.
Because these findings are consistent with similar genotype findings in humans, this further strengthens the use of the rhesus model for studying anxiety-related neuropathologies.
血清素（5-HT）转运体基因启动子区域的长度多态性与5-HT功能改变有关，进而与神经精神疾病如焦虑和抑郁有关。基于行为相似性和存在相似的5-HT转运体基因多态性，非人类灵长类动物已被用作研究人类焦虑相关机制的模型。非人类灵长类动物模型中的应激和威胁情境揭示了5-HT转运体基因型依赖性的区域葡萄糖代谢差异。我们使用恒河猴，研究了血清素转运体基因型与涉及情绪相关病理学的脑区中5-HT转运体结合的关联程度。
对29只恒河猴（猕猴）获取基因型数据和高分辨率PET扫描。在麻醉动物中进行90分钟的[C-11]DASB动态PET扫描，并创建分布体积比（DVR）图像，以作为基于参考区域分析方法进行组间比较的5-HT转运体结合指标。进行区域和体素水平的统计分析，并对灰质概率、性别、年龄和放射性配体质量的解剖差异进行校正。
在涉及焦虑和情绪相关疾病的脑区（杏仁核、纹状体、丘脑、中缝核、颞叶和前额叶皮质）中，比较l/l纯合子与s-携带者时没有显著差异。所有区域的5-HT转运体结合存在显著的性别差异，雌性的DVR比雄性高18%-28%。
由于这些发现与人类的类似基因型发现一致，这进一步加强了恒河猴模型在研究焦虑相关神经病理学中的应用。
