ArticleBrain, behavior, and immunity2015
Synergistic effects of NOD1 or NOD2 and TLR4 activation on mouse sickness behavior in relation to immune and brain activity markers.
Article in Brain, behavior, and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 66 citations in OpenAlex.
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- The disrupted molecular circadian clock of monocytes and macrophages in allergic inflammation.Frontiers in immunology · 2024Article
- Sini San ameliorates lipid metabolism in hyperprolactinemia rat with liver-depression.Current research in food science · 2024Article
- Brain modulation by the gut microbiota: From disease to therapy.Journal of advanced research · 2023Review
- Altered Tryptophan-Kynurenine Pathway in Delirium: A Review of the Current Literature.International journal of molecular sciences · 2023Review
- Glucoraphanin Triggers Rapid Antidepressant Responses in a Rat Model of Beta Amyloid-Induced Depressive-like Behaviour.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Sera of Neuromyelitis Optica Patients Increase BID-Mediated Apoptosis in Astrocytes.International journal of molecular sciences · 2022Article
- Kynurenine Pathway Metabolites as Biomarkers in Alzheimer's Disease.Disease markers · 2022Review
- Neuroinflammation in neurodegenerationFrontiers in immunology · 2022Review
- HPA Axis in the Pathomechanism of Depression and Schizophrenia: New Therapeutic Strategies Based on Its Participation.Brain sciences · 2021Review
- Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells.iScience · 2021Article
- Review
- The anti-parasitic drug miltefosine suppresses activation of human eosinophils and ameliorates allergic inflammation in mice.British journal of pharmacology · 2021Article
- Neurological Infection, Kynurenine Pathway, and Parasitic Infection byFrontiers in immunology · 2021Review
- Review
- Involvement of NFƙB and MAPK signaling pathways in the preventive effects of Ganoderma lucidum on the inflammation of BV-2 microglial cells induced by LPS.Journal of neuroimmunology · 2020Article
- Synergistic Activation of Toll-Like and NOD Receptors by Complementary Antigens as Facilitators of Autoimmune Disease: Review, Model and Novel Predictions.International journal of molecular sciences · 2020Review
- Synergistic Effect of WTC-Particulate Matter and Lysophosphatidic Acid Exposure and the Role of RAGE: In-Vitro and Translational Assessment.International journal of environmental research and public health · 2020Article
- The Mechanism of the Stimforte Effect on the Activation of Target Cell Defense against Viral Infection.Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2020Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Toll-like receptors (TLRs) and nuclear-binding domain (NOD)-like receptors (NLRs) are sensors of bacterial cell wall components to trigger an immune response. The TLR4 agonist lipopolysaccharide (LPS) is a strong immune activator leading to sickness and depressed mood. NOD agonists are less active but can prime immune cells to augment LPS-induced cytokine production. Since the impact of NOD and TLR co-activation in vivo has been little studied, the effects of the NOD1 agonist FK565 and the NOD2 agonist muramyl dipeptide (MDP), alone and in combination with LPS, on immune activation, brain function and sickness behavior were investigated in male C57BL/6N mice. Intraperitoneal injection of FK565 (0.001 or 0.003mg/kg) or MDP (1 or 3mg/kg) 4h before LPS (0.1 or 0.83mg/kg) significantly aggravated and prolonged the LPS-evoked sickness behavior as deduced from a decrease in locomotion, exploration, food intake and temperature. When given alone, FK565 and MDP had only minor effects. The exacerbation of sickness behavior induced by FK565 or MDP in combination with LPS was paralleled by enhanced plasma protein and cerebral mRNA levels of proinflammatory cytokines (IFN-γ, IL-1β, IL-6, TNF-α) as well as enhanced plasma levels of kynurenine. Immunohistochemical visualization of c-Fos in the brain revealed that NOD2 synergism with TLR4 resulted in increased activation of cerebral nuclei relevant to sickness. These data show that NOD1 or NOD2 synergizes with TLR4 in exacerbating the immune, sickness and brain responses to peripheral immune stimulation. Our findings demonstrate that the known interactions of NLRs and TLRs at the immune cell level extend to interactions affecting brain function and behavior.
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