CD40-TNF activation in mice induces extended sickness behavior syndrome co-incident with but not dependent on activation of the kynurenine pathway
| Autor: | René Fuertig, Manuela R. Bizzozzero, Adriano Fontana, Vanessa Hoop, Andreas H. Luippold, Andreas Mueller, Bastian Hengerer, Gregory N. Newman, Hannes Sigrist, Flurin Cathomas, Christopher R. Pryce, Angelo Ceci, Erich Seifritz |
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| Přispěvatelé: | University of Zurich, Pryce, Christopher R |
| Rok vydání: | 2015 |
| Předmět: |
Agonist
Male medicine.medical_specialty Kynurenine pathway medicine.drug_class medicine.medical_treatment Immunology CD40 Ligand Drinking Behavior 610 Medicine & health Motor Activity Behavioral Neuroscience chemistry.chemical_compound Mice Internal medicine 2802 Behavioral Neuroscience Conditioning Psychological medicine Animals Fear conditioning CD40 Antigens Sickness behavior Kynurenine Illness Behavior 2403 Immunology Depressive Disorder Major CD40 biology Behavior Animal Endocrine and Autonomic Systems business.industry Tumor Necrosis Factor-alpha Antibodies Monoclonal Fear Syndrome 3. Good health Mice Inbred C57BL 2807 Endocrine and Autonomic Systems Endocrinology Cytokine chemistry 10054 Clinic for Psychiatry Psychotherapy and Psychosomatics biology.protein Tumor necrosis factor alpha business Signal Transduction |
| Zdroj: | Brain Behavior and Immunity |
| ISSN: | 1090-2139 |
| Popis: | © 2015 Elsevier Inc. The similarity between sickness behavior syndrome (SBS) in infection and autoimmune disorders and certain symptoms in major depressive disorder (MDD) and the high co morbidity of autoimmune disorders and MDD constitutes some of the major evidence for the immune inflammation hypothesis of MDD. CD40 ligand CD40 immune activation is important in host response to infection and in development of autoimmunity. Mice given a single intra peritoneal injection of CD40 agonist antibody (CD40AB) develop SBS for 2 3. days characterized by weight loss and increased sleep effects that are dependent on the cytokine tumor necrosis factor (TNF). Here we report that CD40AB also induces behavioral effects that extend beyond acute SBS and co occur with but are not mediated by kynurenine pathway activation and recovery. CD40AB led to decreased saccharin drinking (days 1 7) and decreased Pavlovian fear conditioning (days 5 6) and was without effect on physical fatigue (day 5). These behavioral effects co occurred with increased plasma and brain levels of kynurenine and its metabolites (days 1 7/8). Co injection of TNF blocker etanercept with CD40AB prevented each of SBS reduced saccharin drinking and kynurenine pathway activation in plasma and brain. Repeated oral administration of a selective indoleamine 23 dioxygenase (IDO) inhibitor blocked activation of the kynurenine pathway but was without effect on SBS and saccharin drinking. This study provides novel evidence that CD40 TNF activation induces deficits in saccharin drinking and Pavlovian fear learning and activates the kynurenine pathway and that CD40 TNF activation of the kynurenine pathway is not necessary for induction of the acute or extended SBS effects. |
| Databáze: | OpenAIRE |
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