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

Autor: Fernanda Laezza, Khalid A Al-Hosaini, Ramesh Elango, Nouf M. Al-Rasheed, Musaad A. Alshammari, Lama Alkahdar, Thomas A. Green, Hazar Yacoub, Tahani K. Alshammari, Abdurahman A. Niazy, Hajar Alghamdi, Mohammed Alswayyed
Rok vydání: 2019
Předmět:
0301 basic medicine
Sucrose
Pharmacology
Disaccharides
Pathology and Laboratory Medicine
Hippocampus
Immune Receptors
Biochemistry
Etanercept
0302 clinical medicine
Cell Signaling
Medicine and Health Sciences
Membrane Receptor Signaling
Toll-like Receptors
Immune Response
Mammals
Toll-like receptor
Multidisciplinary
Immune System Proteins
Behavior
Animal
Depression
Organic Compounds
Eukaryota
Drugs
Brain
Animal Models
Antidepressants
Immune Receptor Signaling
Antidepressive Agents
Chemistry
Experimental Organism Systems
Vertebrates
Physical Sciences
Medicine
Antidepressant
Tumor necrosis factor alpha
Signal transduction
Anatomy
medicine.drug
Signal Transduction
Research Article
Science
Immunology
Carbohydrates
Research and Analysis Methods
Rodents
03 medical and health sciences
Model Organisms
Signs and Symptoms
Diagnostic Medicine
Fluoxetine
Mental Health and Psychiatry
medicine
Animals
TNF Receptor-Associated Factor 6
Inflammation
Environmental enrichment
Depressive Disorder
business.industry
Tumor Necrosis Factor-alpha
Mood Disorders
Organic Chemistry
Organisms
Chemical Compounds
Biology and Life Sciences
Proteins
TLR7
Cell Biology
Rats
Disease Models
Animal
030104 developmental biology
Gene Expression Regulation
Toll-Like Receptor 7
Myeloid Differentiation Factor 88
Amniotes
Animal Studies
business
030217 neurology & neurosurgery
Stress
Psychological
Zdroj: PLoS ONE
PLoS ONE, Vol 14, Iss 10, p e0222818 (2019)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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