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


Autoři: Tahani K. Alshammari aff001;  Hajar Alghamdi aff002;  Thomas A. Green aff003;  Abdurahman Niazy aff004;  Lama Alkahdar aff001;  Nouf Alrasheed aff001;  Khalid Alhosaini aff001;  Mohammed Alswayyed aff005;  Ramesh Elango aff006;  Fernanda Laezza aff003;  Musaad A. Alshammari aff001;  Hazar Yacoub aff001
Působiště autorů: Department of Pharmacology and Toxicology, Pharmacy College, King Saud University, Riyadh, Saudi Arabia aff001;  Pharmacology & Toxicology Graduate Program, Pharmacy College, King Saud University, Riyadh, Saudi Arabia aff002;  Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, United States of America aff003;  Prince Naïf Bin Abdul-Aziz Health Research Center, King Saud University, Riyadh, Saudi Arabia aff004;  Department of Pathology and Laboratory Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia aff005;  Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia aff006
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222818

Souhrn

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 (EI) 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-α 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.

Klíčová slova:

Antidepressants – Depression – Hippocampus – Immune receptor signaling – Inflammation – Rats – Sucrose – Toll-like receptors


Zdroje

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