Assessing the role of toll-like receptor in isolated, standard and enriched housing conditions

被引:14
作者
Alshammari, Tahani K. [1 ]
Alghamdi, Hajar [2 ]
Green, Thomas A. [3 ]
Niazy, Abdurahman [4 ]
Alkahdar, Lama [1 ]
Alrasheed, Nouf [1 ]
Alhosaini, Khalid [1 ]
Alswayyed, Mohammed [5 ]
Elango, Ramesh [6 ]
Laezza, Fernanda [3 ]
Alshammari, Musaad A. [1 ]
Yacoub, Hazar [1 ]
机构
[1] King Saud Univ, Pharm Coll, Dept Pharmacol & Toxicol, Riyadh, Saudi Arabia
[2] King Saud Univ, Pharm Coll, Pharmacol & Toxicol Grad Program, Riyadh, Saudi Arabia
[3] Univ Texas Med Branch, Dept Pharmacol & Toxicol, Galveston, TX 77555 USA
[4] King Saud Univ, Prince Naif Bin Abdul Aziz Hlth Res Ctr, Riyadh, Saudi Arabia
[5] King Saud Univ, King Saud Univ Med City, Coll Med, Dept Pathol & Lab Med, Riyadh, Saudi Arabia
[6] King Saud Univ, Coll Med, Dept Anat, Stem Cell Unit, Riyadh, Saudi Arabia
来源
PLOS ONE | 2019年 / 14卷 / 10期
关键词
ANIMAL-MODEL; DEPRESSION; BRAIN; ETANERCEPT; FLUOXETINE; EXPRESSION; NEUROINFLAMMATION; ANTIDEPRESSANTS; HIPPOCAMPUS; MECHANISMS;
D O I
10.1371/journal.pone.0222818
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Depression is a common psychiatric disorder that has been poorly understood. Consequently, current antidepressant agents have clinical limitations. Until today, most have exhibited the slow onset of therapeutic action and, more importantly, their effect on remission has been minimal. Thus, the need to find new forms of therapeutic intervention is urgent. The inflammation hypothesis of depression is widely acknowledged and is one that theories the relationship between the function of the immune system and its contribution to the neurobiology of depression. In this research, we utilized an environmental isolation (El) approach as a valid animal model of depression, employing biochemical, molecular, and behavioral studies. The aim was to investigate the anti-inflammatory effect of etanercept, a tumor necrosis factor-alpha inhibitor on a toll-like receptor 7 (TLR 7) signaling pathway in a depressive rat model, and compare these actions to fluoxetine, a standard antidepressant agent. The behavioral analysis indicates that depression-related symptoms are reduced after acute administration of fluoxetine and, to a lesser extent, etanercept, and are prevented by enriched environment (EE) housing conditions. Experimental studies were conducted by evaluating immobility time in the force swim test and pleasant feeling in the sucrose preference test. The mRNA expression of the TLR 7 pathway in the hippocampus showed that TLR 7, MYD88, and TRAF6 were elevated in isolated rats compared to the standard group, and that acute treatment with an antidepressant and anti-inflammatory drugs reversed these effects. This research indicates that stressful events have an impact on behavioral well-being, TLR7 gene expression, and the TLR7 pathway. We also found that peripheral administration of etanercept reduces depressive-like behaviour in isolated rats: this could be due to the indirect modulation of the TLR7 pathway and other TLRs in the brain. Furthermore, fluoxetine treatment reversed depressive-like behaviour and molecularly modulated the expression of TLR7, suggesting that fluoxetine exerts antidepressant effects partially by modulating the TLR7 signaling pathway.
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页数:22
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