Brain changes associated with thromboxane receptor antagonist SQ 29,548 treatment in a mouse model.
Brain changes associated with thromboxane receptor antagonist SQ 29,548 treatment in a mouse model.
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小鼠模型中与血栓素受体拮抗剂 SQ 29,548 治疗相关的大脑变化。
DOI：
10.1002/jnr.23578
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发表时间：
2015
影响因子：
4.2
通讯作者：
Combs,ColinK
中科院分区：
文献类型：
--
作者：
Rebel,AndrewA;Urquhart,SiriA;Puig,KendraL;Ghatak,Atreyi;Brose,StephenA;Golovko,MikhailY;Combs,ColinK
本研究的目的是表征选择性血栓素（TP）受体拮抗剂SQ 29,548在C57Bl/6小鼠模型中的行为和生理作用。6月龄时，雄性小鼠按每天2 mg/kg的剂量进行假药或药物腹腔注射，连续3天。在最后一次注射后的第二天，小鼠在采集大脑之前进行行为测试。收集小鼠左半球海马，Western blot分析蛋白质。右脑半球固定并包埋在明胶中，然后连续切片。切片用抗c - Fos抗体免疫染色。对除去海马体的剩余均质脑样本进行前列腺素分析。与假对照组相比，注射SQ 29,548可降低选择性脑前列腺素水平。这与注射SQ 29,548的小鼠边缘区c - Fos免疫反应性的显著增加相关。然而，通过Western blots检测，与假药治疗相比，药物治疗小鼠的相关海马蛋白水平没有显著变化。令人惊讶的是，注射SQ 29,548引起小鼠抑郁和焦虑样行为参数的混合变化。总之，研究结果表明，外周TP受体拮抗剂可以改变脑内前列腺素水平并影响神经元活动，而对行为的影响很小。药物是直接影响神经元还是通过涉及内皮细胞或其他组织的次级途径仍不清楚。©2015 Wiley期刊公司
The purpose of this study was to characterize behavioral and physiological effects of a selective thromboxane (TP) receptor antagonist, SQ 29,548, in the C57Bl/6 mouse model. At 6 months of age, male mice were given either sham or drug i.p. injections for 3 days at a dose of 2 mg/kg each day. On the day after the final injection, mice were subjected to behavioral testing before brain collection. Left hemisphere hippocampi were collected from all mice for protein analysis via Western blot. Right brain hemispheres were fixed and embedded in gelatin and then serially sectioned. The sections were immunostained with anti‐c‐Fos antibodies. Prostaglandin analysis was performed from remaining homogenized brain samples, minus the hippocampi. Injection of SQ 29,548 decreased selective brain prostaglandin levels compared with sham controls. This correlated with robust increases in limbic‐region c‐Fos immunoreactivity in the SQ 29,548‐injected mice. However, drug‐treated mice demonstrated no significant changes in relevant hippocampal protein levels compared with sham treatments, as determined from Western blots. Surprisingly, injection of SQ 29,548 caused mixed changes in parameters of depression and anxiety‐like behavior in the mice. In conclusion, the results indicate that administration of peripheral TP receptor antagonists alters brain levels of prostanoids and influences neuronal activity, with only minimal alterations of behavior. Whether the drug affects neurons directly or through a secondary pathway involving endothelium or other tissues remains unclear. © 2015 Wiley Periodicals, Inc.