Oestradiol alters central 5-HT1A receptor binding potential differences related to psychosocial stress but not differences related to 5-HTTLPR genotype in female rhesus monkeys.
Oestradiol alters central 5-HT1A receptor binding potential differences related to psychosocial stress but not differences related to 5-HTTLPR genotype in female rhesus monkeys.
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DOI：
10.1111/jne.12129
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发表时间：
2014-02
影响因子：
3.2
通讯作者：
Toufexis D
中科院分区：
文献类型：
--
作者：
Michopoulos V;Perez Diaz M;Embree M;Reding K;Votaw JR;Mun J;Voll RJ;Goodman MM;Wilson M;Sanchez M;Toufexis D
雌性猕猴的社会从属地位代表了一个很好的描述模型的慢性心理社会压力。此外，5-羟色胺（5-HT）转运蛋白（5 HTT）基因（SLC 6A 4）调控区的长度多态性（5 HTTLPR）存在于恒河猴中，其与不良结局相关，类似于在具有类似5 HTTLPR多态性的人类中描述的不良结局。本研究确定了社会地位和5 HTTLPR基因型对卵巢切除雌性猴涉及情绪调节和应激反应的脑区5 HT 1A受体结合电位（5 HT 1A BPND）的影响，然后评估了17β-雌二醇（E2）治疗如何改变这些影响。分析的区域包括前额叶皮质[前扣带回（ACC）;内侧前额叶皮质（mPFC）;背外侧前额叶皮质;眶额前额叶皮质]、杏仁核、海马、下丘脑和中缝核。使用p-[18 F]MPPF进行正电子发射断层扫描（PET），以确定非E2和3周E2治疗条件下的5 HT 1A BPND水平。短变异（S-变异）5 HTTLPR基因型产生了显着减少在mPFC的5 HT 1A BPND，无论社会地位，和下属的S-变异的女性表现出减少在ACC.5HTTLPR的这些影响不受E2。此外，E2降低了所有女性中缝背核中的5 HT 1A BPND，而与心理社会压力或5 HTTLPR基因型无关。在非E2条件下，无论5 HTTLPR基因型如何，海马5 HT 1A BPND在下级女性中均减弱，E2的影响正常化。同样，无论5 HTTLPR基因型如何，下级女性下丘脑中的5 HT 1A BPND均显着降低，E2的作用逆转。总之，这些数据表明，E2对中枢5 HT 1A BPND调节的影响可能仅发生在显示没有5 HTTLPR基因型连锁控制5 HT 1A结合的脑区。
Social subordination in female macaques represents a well-described model of chronic psychosocial stress. Additionally, a length polymorphism (5HTTLPR) in the regulatory region of the serotonin (5HT) transporter (5HTT) gene (SLC6A4) is present in rhesus macaques, which has been linked to adverse outcomes similar to what has been described in humans with an analogous 5HTTLPR polymorphism. The present study determined the effects of social status and the 5HTTLPR genotype on 5HT1A receptor binding potential (5HT1A BPND) in brain regions implicated in emotional regulation and stress reactivity in ovariectomised female monkeys, and then assessed how these effects were altered by 17β-oestradiol (E2) treatment. Areas analyzed included the prefrontal cortex [anterior cingulate (ACC); medial prefrontal cortex (mPFC); dorsolateral prefrontal cortex; orbitofrontal prefrontal cortex], amygdala, hippocampus, hypothalamus and raphe nucleui. Positron emission tomography (PET) using p-[18F]MPPF was performed to determine the levels of 5HT1A BPND under a non-E2 and a 3-wk E2 treatment condition. The short variant (s-variant) 5HTTLPR genotype produced a significant reduction in 5HT1A BPND in the mPFC regardless of social status, and subordinate s-variant females showed a reduction in 5HT1A BPND within the ACC. Both these effects of 5HTTLPR were unaffected by E2. Additionally, E2 reduced 5HT1A BPND in the dorsal raphe of all females irrespective of psychosocial stress or 5HTTLPR genotype. Hippocampal 5HT1A BPND was attenuated in subordinate females regardless of 5HTTLPR genotype during the non-E2 condition, an effect that was normalised with E2. Similarly, 5HT1A BPND in the hypothalamus was significantly lower in subordinate females regardless of 5HTTLPR genotype, an effect reversed with E2. Together, the data indicate that the effect of E2 on modulation of central 5HT1A BPND may only occur in brain regions that show no 5HTTLPR genotype-linked control of 5HT1A binding.
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影响因子：
3.3
作者：
Embree, M.;Michopoulos, V.;Votaw, J. R.;Voll, R. J.;Mun, J.;Stehouwer, J. S.;Goodman, M. M.;Wilson, M. E.;Sanchez, M. M.
通讯作者：
Sanchez, M. M.
影响因子：
5.3
作者：
David, SP;Murthy, NV;Grasby, PM
通讯作者：
Grasby, PM
影响因子：
5
作者：
GILBERT, F;BRAZELL, C;STAHL, SM
通讯作者：
STAHL, SM
影响因子：
7.6
作者：
Lu, NZ;Bethea, CL
通讯作者：
Bethea, CL
影响因子：
1.9
作者：
BERNSTEIN, IS;GORDON, TP;ROSE, RM
通讯作者：
ROSE, RM