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Comprehensive Investigation of Metabolic Changes Occurring in the Rat Brain Hippocampus after Fluoxetine Administration Using Two Complementary In Vivo Techniques: Solid Phase Microextraction and Microdialysis
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-10-30 , DOI: 10.1021/acschemneuro.0c00274 Ezel Boyaci 1, 2 , Sofia Lendor 1 , Barbara Bojko 1 , Nathaly Reyes-Garcés 1 , Germán Augusto Gómez-Ríos 1 , Mariola Olkowicz 1 , Mustansir Diwan 3 , Michael Palmer 1 , Clement Hamani 3 , Janusz Pawliszyn 1
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-10-30 , DOI: 10.1021/acschemneuro.0c00274 Ezel Boyaci 1, 2 , Sofia Lendor 1 , Barbara Bojko 1 , Nathaly Reyes-Garcés 1 , Germán Augusto Gómez-Ríos 1 , Mariola Olkowicz 1 , Mustansir Diwan 3 , Michael Palmer 1 , Clement Hamani 3 , Janusz Pawliszyn 1
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Fluoxetine is among the most prescribed antidepressant drugs worldwide. Nevertheless, limited information is known about its definitive mechanism. Although in vivo examinations performed directly in related brain structures can provide more realistic, and therefore more insightful, knowledge regarding the mechanisms and efficacy of this drug, only a few techniques are applicable for in vivo monitoring of metabolic alterations in the brain following an inducement. Among them, solid phase microextraction (SPME) and microdialysis (MD) have emerged as ideal in vivo tools for extraction of information from biosystems. In this investigation, we scrutinized the capabilities of SPME and MD to detect ongoing changes in the brain following acute fluoxetine administration. Sequential in vivo samples were collected simultaneously from male rats’ hippocampi using SPME and MD before drug administration in order to establish a baseline; then samples were collected again following fluoxetine administration for an investigation of small molecule alterations. Our results indicate that MD provides more comprehensive information for polar compounds, while SPME provides superior information with respect to lipids and other medium level polar molecules. Interestingly, in the lipidomic investigation, all dysregulated features were found to be membrane lipids and associated compounds. Moreover, in the metabolomic investigations, dysregulation of hippocampal metabolite levels associated with fatty acid transportation and purine metabolisms were among the most notable findings. Overall, our evaluation of the obtained data corroborates that, when used in tandem, SPME and MD are capable of providing comprehensive information regarding the effect of fluoxetine in targeted brain structures and further elucidating this drug’s mechanisms of action in the brain.
中文翻译：
氟西汀给药后大鼠体内海马代谢变化的综合研究使用两种互补的体内技术：固相微萃取和微透析
氟西汀是全球处方最广泛的抗抑郁药之一。但是，关于其确定机制的信息知之甚少。尽管直接在相关的大脑结构中进行体内检查可以提供有关该药物的机制和功效的更现实的知识，因此可以提供更深入的了解，但只有少数技术可用于体内监测诱导后脑内代谢变化。其中，固相微萃取（SPME）和微透析（MD）已成为从生物系统中提取信息的理想体内工具。在这项调查中，我们详细研究了SPME和MD检测急性氟西汀给药后大脑中正在进行的变化的能力。在给药前，使用SPME和MD同时从雄性大鼠海马体中收集体内样品，以建立基线。然后在服用氟西汀后再次收集样品，以研究小分子改变。我们的结果表明，MD提供了有关极性化合物的更全面的信息，而SPME提供了有关脂质和其他中等水平极性分子的信息。有趣的是，在脂质组学研究中，发现所有失调的特征都是膜脂质和相关化合物。此外，在代谢组学研究中，与脂肪酸运输和嘌呤代谢有关的海马代谢物水平失调是最显着的发现。总体，
更新日期：2020-11-18
中文翻译：
氟西汀给药后大鼠体内海马代谢变化的综合研究使用两种互补的体内技术：固相微萃取和微透析
氟西汀是全球处方最广泛的抗抑郁药之一。但是，关于其确定机制的信息知之甚少。尽管直接在相关的大脑结构中进行体内检查可以提供有关该药物的机制和功效的更现实的知识，因此可以提供更深入的了解，但只有少数技术可用于体内监测诱导后脑内代谢变化。其中，固相微萃取（SPME）和微透析（MD）已成为从生物系统中提取信息的理想体内工具。在这项调查中，我们详细研究了SPME和MD检测急性氟西汀给药后大脑中正在进行的变化的能力。在给药前，使用SPME和MD同时从雄性大鼠海马体中收集体内样品，以建立基线。然后在服用氟西汀后再次收集样品，以研究小分子改变。我们的结果表明，MD提供了有关极性化合物的更全面的信息，而SPME提供了有关脂质和其他中等水平极性分子的信息。有趣的是，在脂质组学研究中，发现所有失调的特征都是膜脂质和相关化合物。此外，在代谢组学研究中，与脂肪酸运输和嘌呤代谢有关的海马代谢物水平失调是最显着的发现。总体，
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