神经影像学与5-HT2C受体多态性：一项针对健康男性先证者的HMPAO单光子发射计算机断层扫描研究，采用5-HT2C受体的间氯苯哌嗪激发试验
Neuroimaging and 5-HT2C receptor polymorphism: a HMPAO-SPECT study in healthy male probands using mCPP-challenge of the 5-HT2C receptor.
作者信息
Kühn K-U, Joe A Y, Meyer K, Reichmann K, Maier W, Rao M L, Reinhardt M J, Biersack H-J, Quednow B B
机构信息
Department of Psychiatry, University Clinic for Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
出版信息
Pharmacopsychiatry. 2004 Nov;37(6):286-91. doi: 10.1055/s-2004-832685.
BACKGROUND
The human 5-HT (2C) receptor gene has been localized on the X chromosome and is expressed in two genetic variants. Whereas previous investigations have suggested that the 5-HT (2C) receptor gene polymorphism is critically involved in the pathogenesis of affective and eating disorders, as yet the functional consequences being associated with the rare serine variant of the 5-HT (2C) receptor in humans are unclear.
METHODS
We explored by HMPAO-SPECT if a challenge with the serotonin agonist mCPP, that interacts mainly with the 5-HT (2C) receptor, provokes different patterns of regional cerebral bloodflow (rCBF) as a function of the genetic variant of the receptor. Thus we studied its action in 16 healthy male volunteers carrying the common 5-HT (2C)-cys-23 receptor gene and 16 healthy male volunteers carrying the less frequent 5-HT (2C)-ser-23 receptor gene.
RESULTS
We found significant differences in rCBF between the two genotypes after mCPP infusion compared to placebo: In the cysteine group rCBF was increased in the left medial prefrontal cortex and decreased in the left anterior cingulate and right medio-temporal cortex, whereas the serine group showed an increase of rCBF in the left medio- and superior-temporal cortex and in cerebellum and a reduced rCBF in the right medial prefrontal cortex. In addition, there was a significant disordinal interaction of the genotype factors and challenge with an increase of rCBF in the serine group and a decrease in the cysteine group in the left motor cortex and calcarine cortex. Additionally, a decrease of rCBF in the serine-group and a simultaneous increase in the cysteine group was found in the right anterior and the left posterior cingulate cortex.
CONCLUSION
These findings suggest that differences in the 5-HT (2C) receptor gene polymorphism has functional consequences due to a different responsiveness of the expressed 5-HT (2C) receptor variants.
背景
人类5-羟色胺（2C）受体基因定位于X染色体，以两种基因变体形式表达。尽管先前的研究表明5-羟色胺（2C）受体基因多态性与情感障碍和饮食失调的发病机制密切相关，但与人类5-羟色胺（2C）受体的罕见丝氨酸变体相关的功能后果仍不清楚。
方法
我们通过HMPAO-SPECT研究了主要与5-羟色胺（2C）受体相互作用的血清素激动剂mCPP激发试验是否会根据受体的基因变体引发不同的局部脑血流（rCBF）模式。因此，我们研究了其在16名携带常见5-羟色胺（2C）-半胱氨酸-23受体基因的健康男性志愿者和16名携带较罕见的5-羟色胺（2C）-丝氨酸-23受体基因的健康男性志愿者中的作用。
结果
与安慰剂相比，在输注mCPP后，我们发现两种基因型之间的rCBF存在显著差异：在半胱氨酸组中，左侧内侧前额叶皮质的rCBF增加，左侧前扣带回和右侧颞中皮质的rCBF减少，而丝氨酸组在左侧颞中及颞上皮质和小脑的rCBF增加，右侧内侧前额叶皮质的rCBF减少。此外，基因型因素与激发试验之间存在显著的非顺序性相互作用，在左侧运动皮质和距状皮质中，丝氨酸组的rCBF增加，半胱氨酸组的rCBF减少。此外，在右侧前扣带回和左侧后扣带回皮质中，发现丝氨酸组的rCBF减少，而半胱氨酸组的rCBF同时增加。
结论
这些发现表明，5-羟色胺（2C）受体基因多态性的差异由于所表达的5-羟色胺（2C）受体变体的不同反应性而具有功能后果。
Zotero 插件