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分析急性社交隔离对大鼠的分子和行为影响。

Analysis of the molecular and behavioral effects of acute social isolation on rats.

机构信息

Department of Pharmacology and Toxicology, Pharmacy College, King Saud University, Saudi Arabia.

Pharmacology & Toxicology Graduate Program, Pharmacy College, King Saud University, Saudi Arabia.

出版信息

Behav Brain Res. 2020 Jan 13;377:112191. doi: 10.1016/j.bbr.2019.112191. Epub 2019 Aug 29.

Abstract

The mechanism underlying depression, anxiety, and stress-related psychiatric disorders is far from understood. The utilization of animal models of anxiety and stress can improve our knowledge of the pathology of these disorders as well as aiding in the identification of pharmacological therapeutic targets. The involvement of inflammation in the pathology of stress-related disorders is widely acknowledged. This study was therefore undertaken to assess depressive and anxiety-like behavior as well as neuroinflammation in acute-isolated rats. The study design comprised two main groups:1) rats in acute isolation (one rat per cage) and 2) standard housing (two rats per cage). Within ten days of acute isolation, we carried behavioral tests including Sucrose Neophobia (SNP), Sucrose Preference Test (SPT), Open field (OPF), and a Forced swim test (FST). In a separate set of experiments, we examined the molecular changes after five days of isolations, we examined the mRNA expression of Toll-like receptors (TLRs) and inflammatory markers in the hippocampal brain region. We found that acute social isolation did not have profound functional effects and the behavioral analysis revealed similarities between the isolated and standard housed rats. However, the molecular studies showed a significant increase in TLRs. An increase in Interleukin 6 (IL-6) and Tumor necrosis factor-alpha (TNF-alpha) was observed in the hippocampus of isolated rats but not the control rats. The results suggest that acute environmental isolation does not significantly affect depressive and anxiety-like behavior but does contribute to upregulations in neuroinflammatory responses. This indicates the initiation of neuronal insults following exposure to short-term isolation.

摘要

抑郁症、焦虑症和与压力相关的精神障碍的发病机制还远未被理解。焦虑和应激动物模型的应用可以增进我们对这些疾病病理的了解,并有助于确定药物治疗靶点。炎症参与应激相关疾病的病理过程已得到广泛认可。因此,本研究旨在评估急性隔离大鼠的抑郁和焦虑样行为以及神经炎症。该研究设计包括两个主要组:1)急性隔离组(每个笼子一只大鼠)和 2)标准饲养组(每个笼子两只大鼠)。在急性隔离十天后,我们进行了行为测试,包括蔗糖厌恶(SNP)、蔗糖偏好测试(SPT)、旷场(OPF)和强迫游泳测试(FST)。在另一组实验中,我们在隔离五天后检查了分子变化,检测了海马脑区 Toll 样受体(TLR)和炎症标志物的 mRNA 表达。我们发现急性社交隔离没有产生深远的功能影响,行为分析显示隔离和标准饲养大鼠之间存在相似性。然而,分子研究显示 TLR 显著增加。在隔离大鼠的海马体中观察到白细胞介素 6(IL-6)和肿瘤坏死因子-α(TNF-α)增加,但在对照大鼠中没有增加。结果表明,急性环境隔离不会显著影响抑郁和焦虑样行为,但会导致神经炎症反应的上调。这表明暴露于短期隔离后会引发神经元损伤。

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