Developmental exposure to the synthetic progestin, 17α-hydroxyprogesterone caproate, disrupts the mesocortical serotonin pathway and alters impulsive decision-making in rats.
Developmental exposure to the synthetic progestin, 17α-hydroxyprogesterone caproate, disrupts the mesocortical serotonin pathway and alters impulsive decision-making in rats.
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DOI：
10.1002/dneu.22847
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发表时间：
2021-09
影响因子：
3
通讯作者：
Wagner CK
中科院分区：
文献类型：
--
作者：
Fahrenkopf A;Li G;Wood RI;Wagner CK
在胎儿发育的关键时期，对有早产风险的女性使用合成的孕激素，即17α-羟孕酮己酸酯（17-OHPC），用于中皮质通路。然而，关于17-OHPC对发育中的胎儿大脑的潜在影响的信息很少。在大鼠模型中，中皮层5-羟色胺通路对孕激素敏感。PR在内侧前额叶皮层（mPFC）的第3层锥体神经元和中缝背核的多巴胺能神经元中表达。本研究验证了以下假设：发育期间暴露于17-OHPC会破坏青春期mPFC的多巴胺能神经支配，并损害成年期由该途径介导的行为。出生后第1-14天给予17-OHPC可降低表层和深层内SERT-IR纤维的密度，并降低出生后第28天前边缘mPFC各层中突触素-IR终扣的密度。此外，在发育过程中暴露于17-OHPC的大鼠在延迟折扣任务中不太可能做出冲动的选择，在中等延迟时间比对照组更经常选择较大的延迟奖励。有趣的是，暴露于17-OHPC的大鼠更有可能无法做出任何选择（即，遗漏增加），而控制在较长的延迟，这表明决策中断。这些结果表明，在17-OHPC的临床使用中有必要进行进一步的研究，以更好地为妊娠期使用阿替米星的风险/获益分析提供信息。
The synthetic progestin, 17α-hydroxyprogesterone caproate (17-OHPC), is administered to women at risk for preterm birth during a critical period of fetal development for mesocortical pathways. Yet, little information is available regarding the potential effects of 17-OHPC on the developing fetal brain. In rat models, the mesocortical serotonin pathway is sensitive to progestins. Progesterone receptor (PR) is expressed in layer 3 pyramidal neurons of medial prefrontal cortex (mPFC) and in serotonergic neurons of the dorsal raphe. The present study tested the hypothesis that exposure to 17-OHPC during development disrupts serotonergic innervation of the mPFC in adolescence and impairs behavior mediated by this pathway in adulthood. Administration of 17-OHPC from postnatal days 1-14 decreased the density of SERT-ir fibers within superficial and deep layers and decreased the density of synaptophysin-ir boutons in all layers of prelimbic mPFC at postnatal day 28. In addition, rats exposed to 17-OHPC during development were less likely to make impulsive choices in the Delay Discounting task, choosing the larger, delayed reward more often than controls at moderate delay times. Interestingly, 17-OHPC exposed rats were more likely to fail to make any choice (i.e., increased omissions) compared to controls at longer delays, suggesting disruptions in decision-making. These results suggest that further investigation is warranted in the clinical use of 17-OHPC to better inform a risk/benefit analysis of progestin use in pregnancy.
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影响因子：
6.1
作者：
BIEGON, A;RECHES, A;MCEWEN, BS
通讯作者：
MCEWEN, BS
影响因子：
2.5
作者：
Birzniece, V;Johansson, IM;Olsson, T
通讯作者：
Olsson, T
影响因子：
9.8
作者：
Caritis, Steve N.;Sharma, Shringi;Jackson, Aimee
通讯作者：
Jackson, Aimee
影响因子：
4.7
作者：
Golub MS;Hackett EP;Hogrefe CE;Leranth C;Elsworth JD;Roth RH
通讯作者：
Roth RH
影响因子：
16.2
作者：
Euston DR;Gruber AJ;McNaughton BL
通讯作者：
McNaughton BL